Influence of sex steroid hormones on the adolescent brain and behavior: An update

PubMed Central

Vigil, Pilar; del Río, Juan Pablo; Carrera, BÁrbara; ArÁnguiz, Florencia C.

2016-01-01

This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical “organizational window” for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary: The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental “organizational window” during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders. PMID:27833209

How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

ERIC Educational Resources Information Center

Fox, Sharon E.; Levitt, Pat; Nelson, Charles A., III.

2010-01-01

Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study a conceptual framework is provided for considering how the structure of early experience gets "under the skin." The study begins with a description of the genetic framework that lays the foundation for brain…

The influence of sex steroids on structural brain maturation in adolescence.

PubMed

Koolschijn, P Cédric M P; Peper, Jiska S; Crone, Eveline A

2014-01-01

Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used high-resolution structural MRI scans from 215 typically developing individuals between ages 8-25, to examine the association between cortical thickness, surface area and (sub)cortical brain volumes with luteinizing hormone, testosterone and estradiol, and pubertal stage based on self-reports. Our results indicate sex-specific differences in testosterone related influences on gray matter volumes of the anterior cingulate cortex after controlling for age effects. No significant associations between subcortical structures and sex hormones were found. Pubertal stage was not a stronger predictor than chronological age for brain anatomical differences. Our findings indicate that sex steroids are associated with cerebral gray matter morphology in a sex specific manner. These hormonal and morphological differences may explain in part differences in brain development between boys and girls.

The developing brain in a multitasking world

PubMed Central

Rothbart, Mary K.; Posner, Michael I.

2015-01-01

To understand the problem of multitasking, it is necessary to examine the brain’s attention networks that underlie the ability to switch attention between stimuli and tasks and to maintain a single focus among distractors. In this paper we discuss the development of brain networks related to the functions of achieving the alert state, orienting to sensory events, and developing self-control. These brain networks are common to everyone, but their efficiency varies among individuals and reflects both genes and experience. Training can alter brain networks. We consider two forms of training: (1) practice in tasks that involve particular networks, and (2) changes in brain state through such practices as meditation that may influence many networks. Playing action video games and multitasking are themselves methods of training the brain that can lead to improved performance but also to overdependence on media activity. We consider both of these outcomes and ideas about how to resist overdependence on media. Overall, our paper seeks to inform the reader about what has been learned about attention that can influence multitasking over the course of development. PMID:25821335

Imaging brain development: the adolescent brain.

PubMed

Blakemore, Sarah-Jayne

2012-06-01

The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.

Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum) on the brain development of newborn rats.

PubMed

Lenzi Almeida, K C; Teles Boaventura, G; Guzmán Silva, M A

2011-01-01

The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n=6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats.

Common genetic variants influence human subcortical brain structures.

PubMed

Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

2015-04-09

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Microglia in the developing brain: a potential target with lifetime effects

PubMed Central

Harry, G. Jean; Kraft, Andrew D.

2012-01-01

Microglia are a heterogeneous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related. PMID:22322212

Maternal adiposity negatively influences infant brain white matter development

USDA-ARS?s Scientific Manuscript database

Objective: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Methods: Diffusion tensor imaging was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age infants from uncomplicat...

Adolescent Brain Development: Current Research and the Impact on Secondary School Counseling Programs

ERIC Educational Resources Information Center

Roaten, Gail K.; Roaten, David J.

2012-01-01

Brain growth and change is a key factor in adolescent development, influencing cognitions, emotions, and behavior. As technology has improved, so has the research on the adolescent brain. School counselors working with adolescents need to be familiar with recent literature to be more effective in their work with middle and high school students.…

Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders.

PubMed

Farr, Olivia M; Tsoukas, Michael A; Mantzoros, Christos S

2015-01-01

Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain sex differences and the organisation of juvenile social play behaviour.

PubMed

Auger, A P; Olesen, K M

2009-06-01

Juvenile social play behaviour is one of the earliest forms of non-mother directed social behaviour in rodents. Juvenile social play behaviour is sexually dimorphic, with males exhibiting higher levels compared to females, making it a useful model to study both social development and sexual differentiation of the brain. As with most sexually dimorphic behaviour, juvenile play behaviour is organised by neonatal steroid hormone exposure. The developmental organisation of juvenile play behaviour also appears to be influenced by the early maternal environment. This review will focus briefly on why and how rats play, some brain regions controlling play behaviour, and how neurotransmitters and the social environment converge within the developing brain to influence sexual differentiation of juvenile play behaviour.

Understanding practice: the factors that influence management of mild traumatic brain injury in the emergency department--a qualitative study using the Theoretical Domains Framework.

PubMed

Tavender, Emma J; Bosch, Marije; Gruen, Russell L; Green, Sally E; Knott, Jonathan; Francis, Jill J; Michie, Susan; O'Connor, Denise A

2014-01-13

Mild traumatic brain injury is a frequent cause of presentation to emergency departments. Despite the availability of clinical practice guidelines in this area, there is variation in practice. One of the aims of the Neurotrauma Evidence Translation program is to develop and evaluate a targeted, theory- and evidence-informed intervention to improve the management of mild traumatic brain injury in Australian emergency departments. This study is the first step in the intervention development process and uses the Theoretical Domains Framework to explore the factors perceived to influence the uptake of four key evidence-based recommended practices for managing mild traumatic brain injury. Semi-structured interviews were conducted with emergency staff in the Australian state of Victoria. The interview guide was developed using the Theoretical Domains Framework to explore current practice and to identify the factors perceived to influence practice. Two researchers coded the interview transcripts using thematic content analysis. A total of 42 participants (9 Directors, 20 doctors and 13 nurses) were interviewed over a seven-month period. The results suggested that (i) the prospective assessment of post-traumatic amnesia was influenced by: knowledge; beliefs about consequences; environmental context and resources; skills; social/professional role and identity; and beliefs about capabilities; (ii) the use of guideline-developed criteria or decision rules to inform the appropriate use of a CT scan was influenced by: knowledge; beliefs about consequences; environmental context and resources; memory, attention and decision processes; beliefs about capabilities; social influences; skills and behavioral regulation; (iii) providing verbal and written patient information on discharge was influenced by: beliefs about consequences; environmental context and resources; memory, attention and decision processes; social/professional role and identity; and knowledge; (iv) the practice of providing brief, routine follow-up on discharge was influenced by: environmental context and resources; social/professional role and identity; knowledge; beliefs about consequences; and motivation and goals. Using the Theoretical Domains Framework, factors thought to influence the management of mild traumatic brain injury in the emergency department were identified. These factors present theoretically based targets for a future intervention.

Differential attentional responding in caesarean versus vaginally delivered infants.

PubMed

Adler, Scott A; Wong-Kee-You, Audrey M B

2015-11-01

Little is known about the role that the birth experience plays in brain and cognitive development. Recent research has suggested that birth experience influences the development of the somatosensory cortex, an area involved in spatial attention to sensory information. In this study, we explored whether differences in spatial attention would occur in infants who had different birth experiences, as occurs for caesarean versus vaginal delivery. Three-month-old infants performed either a spatial cueing task or a visual expectation task. We showed that caesarean-delivered infants' stimulus-driven, reflexive attention was slowed relative to vaginally delivered infants', whereas their cognitively driven, voluntary attention was unaffected. Thus, types of birth experience influence at least one form of infants' attention, and possibly any cognitive process that relies on spatial attention. This study also suggests that birth experience influences the initial state of brain functioning and, consequently, should be considered in our understanding of brain development.

Common genetic variants influence human subcortical brain structures

PubMed Central

Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

2015-01-01

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders.

PubMed

Letra, Liliana; Santana, Isabel

2017-01-01

The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

Robert Sylwester on Electronic Media and Brain Development. Windows to the Mind, Volume 2. [Videotape].

ERIC Educational Resources Information Center

Sylwester, Robert

This videotape explores the influence of electronic media on children's cognitive development. Posing the "cyberworld" as both a window to the greater world and a mirror to the students' world, the first part of the video examines electronic media and the brain's response systems. This part notes the brain's two response systems--the…

Shaping Youngest Minds. Study Guide [and Videotape].

ERIC Educational Resources Information Center

Schrank, Louise Welsh

Noting research indicating that the flow of interaction with infants influences their brain development, this viewer's guide and videotape examine characteristics of early brain development and how parents can positively affect the infant's development in a number of areas. The first part of the viewer's guide provides an overview of the…

P14.21 Can vascular risk factors influence number of brain metastases?

PubMed Central

Berk, B.; Nagel, S.; Kortmann, R.; Hoffmann, K.; Gaudino, C.; Seidel, C.

2017-01-01

Abstract BACKGROUND: Up to 30-40% of patients with solid tumors develop cerebral metastases. Number of cerebral metastases is relevant for treatment and prognosis. However, factors that determine number of metastases are not well defined. Distribution of metastases is influenced by blood vessels and cerebral small vessel disease can reduce number of metastases. Aim of this pilot study was to analyze the influence of vascular risk factors (arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia) and of peripheral arterial occlusive disease (PAOD) on number of brain metastases. METHODS: 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Number of metastases (NoM) was compared between patients with/without vascular risk factors (vasRF). Results: Patients with PAOD had significant less brain metastases than patients without PAOD (NoM=4.43 vs. 6.02, p=0.043), no other single vasRF conferred a significant effect on NoM. NoM differed significantly between different tumor entities. CONCLUSION: Presence of PAOD showed some effect on number of brain metastases implying that tumor-independent vascular factors can influence brain metastasation.

The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

PubMed

Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

2005-09-01

The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group.

Building Your Baby's Brain: A Parent's Guide to the First Five Years = Como estimular el cerebro infantil: Una guia para padres de familia.

ERIC Educational Resources Information Center

Dodge, Diane Trister; Heroman, Cate

Noting that all parents can help their baby's brain to grow, this guide, in English- and Spanish-language versions, explores what science has learned about infant brain development and how parents and caregivers can influence cognitive development. Topics covered include: prenatal care, touching your baby, teaching about feelings and self-control,…

Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

PubMed

Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

2009-01-01

This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

Midsagittal Brain Shape Correlation with Intelligence and Cognitive Performance

ERIC Educational Resources Information Center

Bruner, Emiliano; Martin-Loeches, Manuel; Burgaleta, Miguel; Colom, Roberto

2011-01-01

Brain shape might influence cognitive performance because of the relationships between functions, spatial organization, and differential volumetric development of cortical areas. Here we analyze the relationships between midsagittal brain shape variation and a set of basic psychological measures. Coordinates in 2D from 102 MRI-scanned young adult…

Genetic Mapping of Brain Plasticity Across Development in Williams Syndrome: ERP Markers of Face and Language Processing

PubMed Central

Mills, D. L.; Dai, L.; Fishman, I.; Yam, A.; Appelbaum, L. G.; Galaburda, A.; Bellugi, U.; Korenberg, J. R.

2014-01-01

In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, ERPs from large samples of children, adolescents, and adults with the full genetic deletion for WS were compared to typically developing controls, and two adults with partial deletions for WS. Studies 1 and 2 identified ERP markers of brain plasticity in WS across development. Study 3 suggested that in adults with partial deletions for WS, specific genes may be differentially implicated in face and language processing. PMID:24219698

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development.

PubMed

Bakker, J; Brock, O

2010-07-01

A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female-typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male-typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of alpha-fetoprotein, whereas female-typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.

Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development.

PubMed

Bramble, Matthew S; Lipson, Allen; Vashist, Neerja; Vilain, Eric

2017-01-02

Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α-reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α-reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prenatal Influences on the Brain.

ERIC Educational Resources Information Center

Eliot, Lise

2002-01-01

Gives an overview of embryology and prenatal brain, sensory, and motor development. Includes discussion of maternal nutrition, chemical exposure, prenatal drug and alcohol hazards, cigarette smoking, and some causes of neural tube defects and premature birth. (Author/KB)

We have got you 'covered': how the meninges control brain development.

PubMed

Siegenthaler, Julie A; Pleasure, Samuel J

2011-06-01

The meninges have traditionally been viewed as specialized membranes surrounding and protecting the adult brain from injury. However, there is increasing evidence that the fetal meninges play important roles during brain development. Through the release of diffusible factors, the meninges influence the proliferative and migratory behaviors of neural progenitors and neurons in the forebrain and hindbrain. Meningeal cells also secrete and organize the pial basement membrane (BM), a critical anchor point for the radially oriented fibers of neuroepithelial stem cells. With its emerging role in brain development, the potential that defects in meningeal development may underlie certain congenital brain abnormalities in humans should be considered. In this review, we will discuss what is known about assembly of the fetal meninges and review the role of meningeal-derived proteins in mouse and human brain development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diet and Gender Influences on Processing and Discrimination of Speech Sounds in 3- and 6-Month-Old Infants: A Developmental ERP Study

ERIC Educational Resources Information Center

Pivik, R. T.; Andres, Aline; Badger, Thomas M.

2011-01-01

Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either…

Aging with a traumatic brain injury: Could behavioral morbidities and endocrine symptoms be influenced by microglial priming?

PubMed

Ziebell, Jenna M; Rowe, Rachel K; Muccigrosso, Megan M; Reddaway, Jack T; Adelson, P David; Godbout, Jonathan P; Lifshitz, Jonathan

2017-01-01

A myriad of factors influence the developmental and aging process and impact health and life span. Mounting evidence indicates that brain injury, even moderate injury, can lead to lifetime of physical and mental health symptoms. Therefore, the purpose of this mini-review is to discuss how recovery from traumatic brain injury (TBI) depends on age-at-injury and how aging with a TBI affects long-term recovery. TBI initiates pathophysiological processes that dismantle circuits in the brain. In response, reparative and restorative processes reorganize circuits to overcome the injury-induced damage. The extent of circuit dismantling and subsequent reorganization depends as much on the initial injury parameters as other contributing factors, such as genetics and age. Age-at-injury influences the way the brain is able to repair itself, as a result of developmental status, extent of cellular senescence, and injury-induced inflammation. Moreover, endocrine dysfunction can occur with TBI. Depending on the age of the individual at the time of injury, endocrine dysfunction may disrupt growth, puberty, influence social behaviors, and possibly alter the inflammatory response. In turn, activation of microglia, the brain's immune cells, after injury may continue to fuel endocrine dysfunction. With age, the immune system develops and microglia become primed to subsequent challenges. Sustained inflammation and microglial activation can continue for weeks to months post-injury. This prolonged inflammation can influence developmental processes, behavioral performance and age-related decline. Overall, brain injury may influence the aging process and expedite glial and neuronal alterations that impact mental health. Copyright © 2016 Elsevier Inc. All rights reserved.

Innovative and Brain-Friendly Strategies for Building a Therapeutic Alliance with Adolescents

ERIC Educational Resources Information Center

Roaten, Gail K.

2011-01-01

Brain growth and change are key factors in adolescent development and influence cognitions, emotions, and behavior. Much of the research on the adolescent brain is fairly recent, and mental health practitioners working with adolescents must have knowledge about these changes to more effectively engage their young clients in therapy. The…

Observed Measures of Negative Parenting Predict Brain Development during Adolescence.

PubMed

Whittle, Sarah; Vijayakumar, Nandita; Dennison, Meg; Schwartz, Orli; Simmons, Julian G; Sheeber, Lisa; Allen, Nicholas B

2016-01-01

Limited attention has been directed toward the influence of non-abusive parenting behaviour on brain structure in adolescents. It has been suggested that environmental influences during this period are likely to impact the way that the brain develops over time. The aim of this study was to investigate the association between aggressive and positive parenting behaviors on brain development from early to late adolescence, and in turn, psychological and academic functioning during late adolescence, using a multi-wave longitudinal design. Three hundred and sixty seven magnetic resonance imaging (MRI) scans were obtained over three time points from 166 adolescents (11-20 years). At the first time point, observed measures of maternal aggressive and positive behaviors were obtained. At the final time point, measures of psychological and academic functioning were obtained. Results indicated that a higher frequency of maternal aggressive behavior was associated with alterations in the development of right superior frontal and lateral parietal cortical thickness, and of nucleus accumbens volume, in males. Development of the superior frontal cortex in males mediated the relationship between maternal aggressive behaviour and measures of late adolescent functioning. We suggest that our results support an association between negative parenting and adolescent functioning, which may be mediated by immature or delayed brain maturation.

Observed Measures of Negative Parenting Predict Brain Development during Adolescence

PubMed Central

Whittle, Sarah; Vijayakumar, Nandita; Dennison, Meg; Schwartz, Orli; Simmons, Julian G.; Sheeber, Lisa; Allen, Nicholas B.

2016-01-01

Limited attention has been directed toward the influence of non-abusive parenting behaviour on brain structure in adolescents. It has been suggested that environmental influences during this period are likely to impact the way that the brain develops over time. The aim of this study was to investigate the association between aggressive and positive parenting behaviors on brain development from early to late adolescence, and in turn, psychological and academic functioning during late adolescence, using a multi-wave longitudinal design. Three hundred and sixty seven magnetic resonance imaging (MRI) scans were obtained over three time points from 166 adolescents (11–20 years). At the first time point, observed measures of maternal aggressive and positive behaviors were obtained. At the final time point, measures of psychological and academic functioning were obtained. Results indicated that a higher frequency of maternal aggressive behavior was associated with alterations in the development of right superior frontal and lateral parietal cortical thickness, and of nucleus accumbens volume, in males. Development of the superior frontal cortex in males mediated the relationship between maternal aggressive behaviour and measures of late adolescent functioning. We suggest that our results support an association between negative parenting and adolescent functioning, which may be mediated by immature or delayed brain maturation. PMID:26824348

Special issue on the teenage brain: Sensitivity to social evaluation

PubMed Central

Somerville, Leah H.

2013-01-01

Relative to childhood, peer relationships take on a heightened importance during adolescence. Might adolescents be highly attuned to information that concerns when and how they are being evaluated, and what their peers think of them? This review evaluates how continuing brain development - which influences brain function - partially explains or reflects adolescents’ attunement to social evaluation. Though preliminary, evidence is mounting to suggest that while processing information relevant to social evaluation and the internal states of other people, adolescents respond with greater emotional intensity and corresponding nonlinear recruitment of socioaffective brain circuitry. This review highlights research findings that relate trajectories of brain development and social behavior, and discusses promising avenues of future research that will inform how brain development might lead adolescents sensitized to social evaluation. PMID:24761055

Dietary docosahexaenoic acid supplementation modulates hippocampal development in the Pemt-/- mouse.

PubMed

da Costa, Kerry-Ann; Rai, Kiranmai S; Craciunescu, Corneliu N; Parikh, Komal; Mehedint, Mihai G; Sanders, Lisa M; McLean-Pottinger, Audrey; Zeisel, Steven H

2010-01-08

The development of fetal brain is influenced by nutrients such as docosahexaenoic acid (DHA, 22:6) and choline. Phosphatidylethanolamine-N-methyltransferase (PEMT) catalyzes the biosynthesis of phosphatidylcholine from phosphatidylethanolamine enriched in DHA and many humans have functional genetic polymorphisms in the PEMT gene. Previously, it was reported that Pemt(-/-) mice have altered hippocampal development. The present study explores whether abnormal phosphatidylcholine biosynthesis causes altered incorporation of DHA into membranes, thereby influencing brain development, and determines whether supplemental dietary DHA can reverse some of these changes. Pregnant C57BL/6 wild type (WT) and Pemt(-/-) mice were fed a control diet, or a diet supplemented with 3 g/kg of DHA, from gestational day 11 to 17. Brains from embryonic day 17 fetuses derived from Pemt(-/-) dams fed the control diet had 25-50% less phospholipid-DHA as compared with WT (p < 0.05). Also, they had 60% more neural progenitor cell proliferation (p < 0.05), 60% more neuronal apoptosis (p < 0.01), and 30% less calretinin expression (p < 0.05; a marker of neuronal differentiation) in the hippocampus compared with WT. The DHA-supplemented diet increased fetal brain Pemt(-/-) phospholipid-DHA to WT levels, and abrogated the neural progenitor cell proliferation and apoptosis differences. Although this diet did not change proliferation in the WT group, it halved the rate of apoptosis (p < 0.05). In both genotypes, the DHA-supplemented diet increased calretinin expression 2-fold (p < 0.05). These results suggest that the changes in hippocampal development in the Pemt(-/-) mouse could be mediated by altered DHA incorporation into membrane phospholipids, and that maternal dietary DHA can influence fetal brain development.

Cerebral Low-Molecular Metabolites Influenced by Intestinal Microbiota: A Pilot Study

PubMed Central

Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

2013-01-01

Recent studies suggest that intestinal microbiota influences gut-brain communication. In this study, we aimed to clarify the influence of intestinal microbiota on cerebral metabolism. We analyzed the cerebral metabolome of germ-free (GF) mice and Ex-GF mice, which were inoculated with suspension of feces obtained from specific pathogen-free mice, using capillary electrophoresis with time-of-flight mass spectrometry (CE-TOFMS). CE-TOFMS identified 196 metabolites from the cerebral metabolome in both GF and Ex-GF mice. The concentrations of 38 metabolites differed significantly (p < 0.05) between GF and Ex-GF mice. Approximately 10 of these metabolites are known to be involved in brain function, whilst the functions of the remainder are unclear. Furthermore, we observed a novel association between cerebral glycolytic metabolism and intestinal microbiota. Our work shows that cerebral metabolites are influenced by normal intestinal microbiota through the microbiota-gut-brain axis, and indicates that normal intestinal microbiota closely connected with brain health and disease, development, attenuation, learning, memory, and behavior. PMID:23630473

In Utero Administration of Drugs Targeting Microglia Improves the Neurodevelopmental Outcome Following Cytomegalovirus Infection of the Rat Fetal Brain

PubMed Central

Cloarec, Robin; Bauer, Sylvian; Teissier, Natacha; Schaller, Fabienne; Luche, Hervé; Courtens, Sandra; Salmi, Manal; Pauly, Vanessa; Bois, Emilie; Pallesi-Pocachard, Emilie; Buhler, Emmanuelle; Michel, François J.; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N.; Bruneau, Nadine; Szepetowski, Pierre

2018-01-01

Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain. PMID:29559892

Finding language in the matter of the brain: origins of the clinical aphasia examination.

PubMed

Roth, Heidi L

2002-12-01

The origins of the aphasia examination can be traced back to the 19th century when physicians and scientists began to understand how higher mental functions such as language could be localized in the brain. Paul Broca, Carl Wernicke, and Hughlings Jackson developed different models of brain function, and each contributed important insights to the study of aphasia. Broca's contributions were influenced by the fundamental question of whether higher mental function could be localized in the brain at all; Wernicke's contributions were influenced by an attempt to unite more mechanistic and physiological principles to a model of higher brain functions; and Jackson's contributions were influenced by British association psychology. In addition to reviewing the origins of the aphasia examination, this article reviews the historical context in which these contributors worked, the factors that affected the reception of their views, and the manner in which their views have affected the aphasia examination and understanding of aphasia today.

Adolescent brain development, substance use, and psychotherapeutic change.

PubMed

Wetherill, Reagan; Tapert, Susan F

2013-06-01

Adolescence is a unique developmental period characterized by major physiological, psychological, social, and brain changes, as well as an increased incidence of maladaptive, addictive behaviors. With the use of MRI techniques, researchers have been able to provide a better understanding of adolescent brain maturation and how neurodevelopment affects cognition and behavior. This review discusses adolescent brain development and its potential influence on psychotherapeutic change. We focus on cognitive-behavioral and mindfulness-based approaches for treating substance use and highlight potential brain mechanisms underlying response to psychotherapy. Finally, we discuss integrative neuroimaging and treatment studies and potential opportunities for advancing the treatment of adolescent addictive behaviors. 2013 APA, all rights reserved

Is the ferret a suitable species for studying perinatal brain injury?

PubMed Central

Empie, Kristen; Rangarajan, Vijayeta; Juul, Sandra E.

2016-01-01

Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies. PMID:26102988

Choline: Dietary Requirements and Role in Brain Development.

PubMed

Sanders, Lisa M; Zeisel, Steven H

2007-01-01

Choline is needed for the maintenance of the structural integrity and signaling functions of cell membranes, for neurotransmission, and for transport of lipids and as a source of methyl groups. Choline can be made de novo in the body, but some individuals must also obtain choline in the diet to prevent deficiency symptoms. A number of environmental and genetic factors influence dietary requirements for choline, and average intakes in the population vary widely. Therefore, certain individuals may be at greater risk of choline deficiency. Choline is critical during fetal development, particularly during the development of the brain, where it can influence neural tube closure and lifelong memory and learning functions.

Plasticity-related genes in brain development and amygdala-dependent learning.

PubMed

Ehrlich, D E; Josselyn, S A

2016-01-01

Learning about motivationally important stimuli involves plasticity in the amygdala, a temporal lobe structure. Amygdala-dependent learning involves a growing number of plasticity-related signaling pathways also implicated in brain development, suggesting that learning-related signaling in juveniles may simultaneously influence development. Here, we review the pleiotropic functions in nervous system development and amygdala-dependent learning of a signaling pathway that includes brain-derived neurotrophic factor (BDNF), extracellular signaling-related kinases (ERKs) and cyclic AMP-response element binding protein (CREB). Using these canonical, plasticity-related genes as an example, we discuss the intersection of learning-related and developmental plasticity in the immature amygdala, when aversive and appetitive learning may influence the developmental trajectory of amygdala function. We propose that learning-dependent activation of BDNF, ERK and CREB signaling in the immature amygdala exaggerates and accelerates neural development, promoting amygdala excitability and environmental sensitivity later in life. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

How environment and genes shape the adolescent brain.

PubMed

Paus, Tomáš

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". This review provides a conceptual framework for the study of factors--in our genes and environment--that shape the adolescent brain. I start by pointing out that brain phenotypes obtained with magnetic resonance imaging are complex traits reflecting the interplay of genes and the environment. In some cases, variations in the structural phenotypes observed during adolescence have their origin in the pre-natal or early post-natal periods. I then emphasize the bidirectional nature of brain-behavior relationships observed during this period of human development, where function may be more likely to influence structure rather than vice versa. In the main part of this article, I review our ongoing work on the influence of gonadal hormones on the adolescent brain. I also discuss the importance of social context and brain plasticity on shaping the relevant neural circuits. Copyright © 2013 Elsevier Inc. All rights reserved.

Developmental imaging genetics: linking dopamine function to adolescent behavior.

PubMed

Padmanabhan, Aarthi; Luna, Beatriz

2014-08-01

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice.

PubMed

Maruoka, Takashi; Kodomari, Ikuko; Yamauchi, Rena; Wada, Etsuko; Wada, Keiji

2009-04-17

The maternal environment is thought to be important for fetal brain development. However, the effects of maternal environment are not fully understood. Here, we investigated whether enrichment of the maternal environment can influence prenatal brain development and postnatal behaviors in mice. An enriched environment is a housing condition with several objects such as a running wheel, tube and ladder, which are thought to increase sensory, cognitive and motor stimulation in rodents compared with standard housing conditions. First, we measured the number of BrdU-positive cells in the hippocampal dentate gyrus of fetuses from pregnant dams housed in an enriched environment. Our results revealed that maternal enrichment influences cell proliferation in the hippocampus of female, but not male, fetuses. Second, we used the open-field test to investigate postnatal behaviors in the offspring of dams housed in the enriched environment during pregnancy. We found that maternal enrichment significantly affects the locomotor activity and time spent in the center of the open-field in female, but not male, offspring. These results indicate that maternal enrichment influences prenatal brain development and postnatal behaviors in female offspring.

Puberty and structural brain development in humans.

PubMed

Herting, Megan M; Sowell, Elizabeth R

2017-01-01

Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

Puberty and structural brain development in humans

PubMed Central

Herting, Megan M.; Sowell, Elizabeth R.

2017-01-01

Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual-based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. PMID:28007528

Influence of maternal thyroid hormones during gestation on fetal brain development

PubMed Central

Moog, Nora K.; Entringer, Sonja; Heim, Christine; Wadhwa, Pathik D.; Kathmann, Norbert; Buss, Claudia

2015-01-01

Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention. PMID:26434624

Sex steroids and human behavior: prenatal androgen exposure and sex-typical play behavior in children.

PubMed

Hines, Melissa

2003-12-01

Gonadal hormones, particularly androgens, direct certain aspects of brain development and exert permanent influences on sex-typical behavior in nonhuman mammals. Androgens also influence human behavioral development, with the most convincing evidence coming from studies of sex-typical play. Girls exposed to unusually high levels of androgens prenatally, because they have the genetic disorder, congenital adrenal hyperplasia (CAH), show increased preferences for toys and activities usually preferred by boys, and for male playmates, and decreased preferences for toys and activities usually preferred by girls. Normal variability in androgen prenatally also has been related to subsequent sex-typed play behavior in girls, and nonhuman primates have been observed to show sex-typed preferences for human toys. These findings suggest that androgen during early development influences childhood play behavior in humans at least in part by altering brain development.

Mechanisms that Underlie Co-variation of the Brain and Face

PubMed Central

Marcucio, Ralph S.; Young, Nathan M.; Hu, Diane; Hallgrimsson, Benedikt

2011-01-01

The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this paper we describe factors that are active between development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through direct structural interactions. Second, there is the molecular influence of the brain, which signals to facial tissues to establish signaling centers that regulate patterned growth. Importantly, subtle alterations to these physical or molecular interactions may contribute to both normal and abnormal variation. These interactions are therefore critical to our understanding of how a diversity of facial morphologies can be generated both within species and across evolutionary time. PMID:21381182

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

PubMed

Platonov, I A; Anashchenkova, T A; Andreeva, T A

2008-01-01

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

Sex-related variation in human behavior and the brain

PubMed Central

Hines, Melissa

2010-01-01

Male and female fetuses differ in testosterone concentrations beginning as early as week 8 of gestation. This early hormone difference exerts permanent influences on brain development and behavior. Contemporary research shows that hormones are particularly important for the development of sex-typical childhood behavior, including toy choices, which until recently were thought to result solely from sociocultural influences. Prenatal testosterone exposure also appears to influence sexual orientation and gender identity, as well as some, but not all, sex-related cognitive, motor and personality characteristics. Neural mechanisms responsible for these hormone-induced behavioral outcomes are beginning to be identified, and current evidence suggests involvement of the hypothalamus and amygdala, as well as interhemispheric connectivity, and cortical areas involved in visual processing. PMID:20724210

Musical training influences linguistic abilities in 8-year-old children: more evidence for brain plasticity.

PubMed

Moreno, Sylvain; Marques, Carlos; Santos, Andreia; Santos, Manuela; Castro, São Luís; Besson, Mireille

2009-03-01

We conducted a longitudinal study with 32 nonmusician children over 9 months to determine 1) whether functional differences between musician and nonmusician children reflect specific predispositions for music or result from musical training and 2) whether musical training improves nonmusical brain functions such as reading and linguistic pitch processing. Event-related brain potentials were recorded while 8-year-old children performed tasks designed to test the hypothesis that musical training improves pitch processing not only in music but also in speech. Following the first testing sessions nonmusician children were pseudorandomly assigned to music or to painting training for 6 months and were tested again after training using the same tests. After musical (but not painting) training, children showed enhanced reading and pitch discrimination abilities in speech. Remarkably, 6 months of musical training thus suffices to significantly improve behavior and to influence the development of neural processes as reflected in specific pattern of brain waves. These results reveal positive transfer from music to speech and highlight the influence of musical training. Finally, they demonstrate brain plasticity in showing that relatively short periods of training have strong consequences on the functional organization of the children's brain.

Media use and brain development during adolescence.

PubMed

Crone, Eveline A; Konijn, Elly A

2018-02-21

The current generation of adolescents grows up in a media-saturated world. However, it is unclear how media influences the maturational trajectories of brain regions involved in social interactions. Here we review the neural development in adolescence and show how neuroscience can provide a deeper understanding of developmental sensitivities related to adolescents' media use. We argue that adolescents are highly sensitive to acceptance and rejection through social media, and that their heightened emotional sensitivity and protracted development of reflective processing and cognitive control may make them specifically reactive to emotion-arousing media. This review illustrates how neuroscience may help understand the mutual influence of media and peers on adolescents' well-being and opinion formation.

The Cerebellum, Sensitive Periods, and Autism

PubMed Central

Wang, Samuel S.-H.; Kloth, Alexander D.; Badura, Aleksandra

2014-01-01

Cerebellar research has focused principally on adult motor function. However, the cerebellum also maintains abundant connections with nonmotor brain regions throughout postnatal life. Here we review evidence that the cerebellum may guide the maturation of remote nonmotor neural circuitry and influence cognitive development, with a focus on its relationship with autism. Specific cerebellar zones influence neocortical substrates for social interaction, and we propose that sensitive-period disruption of such internal brain communication can account for autism's key features. PMID:25102558

Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits

PubMed Central

Niwa, Minae; Kamiya, Atsushi; Murai, Rina; Kubo, Ken-ichiro; Gruber, Aaron J; Tomita, Kenji; Lu, Lingling; Tomisato, Shuta; Jaaro-Peled, Hanna; Seshadri, Saurav; Hiyama, Hideki; Huang, Beverly; Kohda, Kazuhisa; Noda, Yukihiro; O’Donnell, Patricio; Nakajima, Kazunori; Sawa, Akira; Nabeshima, Toshitaka

2011-01-01

SUMMARY Adult brain function and behavior are influenced by neuronal network formation during development. Genetic susceptibility factors for adult psychiatric illnesses, such as Neuregulin-1 and Disrupted-in-Schizophrenia-1 (DISC1), influence adult high brain functions, including cognition and information processing. These factors have roles during neurodevelopment and are likely to cooperate, forming “pathways” or “signalosomes.” Here we report the potential to generate an animal model via in utero gene transfer in order to address an important question of how nonlethal deficits in early development may affect postnatal brain maturation and high brain functions in adulthood, which are impaired in various psychiatric illnesses, such as schizophrenia. We show that transient knockdown of DISC1 in the pre- and peri-natal stages, specifically in a lineage of pyramidal neurons mainly in the prefrontal cortex, leads to selective abnormalities in postnatal mesocortical dopaminergic maturation and behavioral abnormalities associated with disturbed cortical neurocircuitry after puberty. PMID:20188653

[Transsexualism as a clinical symptom of true hermaphroditism].

PubMed

Derevianko, I M; Derevianko, T I; Abdul'menov, R R

2008-01-01

Transsexualism is incorrectly thought to be a disease of sexual centers (zones) of the brain but these sexual centers in the brain operate only in response to action of sexual hormones (androgens or estrogens) which are produced in the gonads and delivered to the brain by blood. In hermaphroditism the brain receives both androgens and estrogens. Transsexualism syndrome develops in cases when all sexual organs develop under the influence of one sex while sexual psychoorientation, sexual autoidentification and sexual behavior form under the influence of hormones of the other sex. Therefore, treatment of this syndrome should not consist of surgical correction of the sex according to psychic behavior of the patient but should be directed to detection of the gonad (or gonadal tissue) causing abnormal behavior and its removal. Gonad corresponding to sexual organs of the patient should be preserved. Of 19 patients with true hermaphroditism and 199 patients with false hermaphroditism observed by the authors 4 patients with true hermaphroditism had transsexualism.

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.

Heritability of volumetric brain changes and height in children entering puberty.

PubMed

van Soelen, Inge L C; Brouwer, Rachel M; van Baal, G Caroline M; Schnack, Hugo G; Peper, Jiska S; Chen, Lei; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

2013-03-01

The human brain undergoes structural changes in children entering puberty, while simultaneously children increase in height. It is not known if brain changes are under genetic control, and whether they are related to genetic factors influencing the amount of overall increase in height. Twins underwent magnetic resonance imaging brain scans at age 9 (N = 190) and 12 (N = 125). High heritability estimates were found at both ages for height and brain volumes (49-96%), and high genetic correlation between ages were observed (r(g) > 0.89). With increasing age, whole brain (+1.1%), cerebellum (+4.2%), cerebral white matter (+5.1%), and lateral ventricle (+9.4%) volumes increased, and third ventricle (-4.0%) and cerebral gray matter (-1.6%) volumes decreased. Children increased on average 13.8 cm in height (9.9%). Genetic influences on individual difference in volumetric brain and height changes were estimated, both within and across traits. The same genetic factors influenced both cerebral (20% heritable) and cerebellar volumetric changes (45%). Thus, the extent to which changes in cerebral and cerebellar volumes are heritable in children entering puberty are due to the same genes that influence change in both structures. The increase in height was heritable (73%), and not associated with cerebral volumetric change, but positively associated with cerebellar volume change (r(p) = 0.24). This association was explained by a genetic correlation (r(g) = 0.48) between height and cerebellar change. Brain and body each expand at their own pace and through separate genetic pathways. There are distinct genetic processes acting on structural brain development, which cannot be explained by genetic increase in height. Copyright © 2011 Wiley Periodicals, Inc.

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity.

PubMed

Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P; Nir, Talia M; Toga, Arthur W; Jack, Clifford R; Saykin, Andrew J; Green, Robert C; Weiner, Michael W; Medland, Sarah E; Montgomery, Grant W; Hansell, Narelle K; McMahon, Katie L; de Zubicaray, Greig I; Martin, Nicholas G; Wright, Margaret J; Thompson, Paul M

2013-03-19

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain

PubMed Central

Lumniczky, Katalin; Szatmári, Tünde; Sáfrány, Géza

2017-01-01

Radiation-induced late brain injury consisting of vascular abnormalities, demyelination, white matter necrosis, and cognitive impairment has been described in patients subjected to cranial radiotherapy for brain tumors. Accumulating evidence suggests that various degrees of cognitive deficit can develop after much lower doses of ionizing radiation, as well. The pathophysiological mechanisms underlying these alterations are not elucidated so far. A permanent deficit in neurogenesis, chronic microvascular alterations, and blood–brain barrier dysfunctionality are considered among the main causative factors. Chronic neuroinflammation and altered immune reactions in the brain, which are inherent complications of brain irradiation, have also been directly implicated in the development of cognitive decline after radiation. This review aims to give a comprehensive overview on radiation-induced immune alterations and inflammatory reactions in the brain and summarizes how these processes can influence cognitive performance. The available data on the risk of low-dose radiation exposure in the development of cognitive impairment and the underlying mechanisms are also discussed. PMID:28529513

A mass spectrometry imaging approach for investigating how drug-drug interactions influence drug blood-brain barrier permeability.

PubMed

Vallianatou, Theodosia; Strittmatter, Nicole; Nilsson, Anna; Shariatgorji, Mohammadreza; Hamm, Gregory; Pereira, Marcela; Källback, Patrik; Svenningsson, Per; Karlgren, Maria; Goodwin, Richard J A; Andrén, Per E

2018-05-15

There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies. Copyright © 2018. Published by Elsevier Inc.

Factors Influencing Cerebral Plasticity in the Normal and Injured Brain

PubMed Central

Kolb, Bryan; Teskey, G. Campbell; Gibb, Robbin

2010-01-01

An important development in behavioral neuroscience in the past 20 years has been the demonstration that it is possible to stimulate functional recovery after cerebral injury in laboratory animals. Rodent models of cerebral injury provide an important tool for developing such rehabilitation programs. The models include analysis at different levels including detailed behavioral paradigms, electrophysiology, neuronal morphology, protein chemistry, and epigenetics. A significant challenge for the next 20 years will be the translation of this work to improve the outcome from brain injury and disease in humans. Our goal in the article will be to synthesize the multidisciplinary laboratory work on brain plasticity and behavior in the injured brain to inform the development of rehabilitation programs. PMID:21120136

The International Society for Developmental Psychobiology Annual Meeting Symposium: Impact of Early Life Experiences on Brain and Behavioral Development

PubMed Central

Sullivan, Regina; Wilson, Donald A.; Feldon, Joram; Yee, Benjamin K.; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina

2007-01-01

Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, ajuvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism’s developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health. PMID:17016842

Endoscopic and minimally invasive microsurgical approaches for treating brain tumor patients.

PubMed

Badie, Behnam; Brooks, Nathaniel; Souweidane, Mark M

2004-01-01

Recent developments in neuroendoscopy and minimally invasive procedures have greatly impacted the diagnosis and treatment of brain tumors. In this paper, we will review these innovations and discuss how they have influenced our approach to the treatment of intraventricular and pituitary tumors. Finally, the concept of keyhole neurosurgery is illustrated by discussing 'eyebrow orbitotomy' approach as an example. As noninvasive therapeutic alternative become available, future neurosurgeons will be challenged to develop effective and less invasive surgical approaches for the diagnosis and treatment of patients will brain tumors.

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

PubMed

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

PubMed Central

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PMID:17901127

A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply

PubMed Central

Menshawi, Khaled; Mohr, Jay P

2015-01-01

The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants. PMID:26060802

Deep-brain-stimulation does not impair deglutition in Parkinson's disease.

PubMed

Lengerer, Sabrina; Kipping, Judy; Rommel, Natalie; Weiss, Daniel; Breit, Sorin; Gasser, Thomas; Plewnia, Christian; Krüger, Rejko; Wächter, Tobias

2012-08-01

A large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e., aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD. Videofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The 'New Zealand index for multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. Preoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency. In Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Turner Syndrome: Neuroimaging Findings--Structural and Functional

ERIC Educational Resources Information Center

Mullaney, Ronan; Murphy, Declan

2009-01-01

Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including…

Fluorescence Imaging/Agents in Tumor Resection.

PubMed

Stummer, Walter; Suero Molina, Eric

2017-10-01

Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The impact of poverty on the development of brain networks

PubMed Central

Lipina, Sebastián J.; Posner, Michael I.

2012-01-01

Although the study of brain development in non-human animals is an old one, recent imaging methods have allowed non-invasive studies of the gray and white matter of the human brain over the lifespan. Classic animal studies show clearly that impoverished environments reduce cortical gray matter in relation to complex environments and cognitive and imaging studies in humans suggest which networks may be most influenced by poverty. Studies have been clear in showing the plasticity of many brain systems, but whether sensitivity to learning differs over the lifespan and for which networks is still unclear. A major task for current research is a successful integration of these methods to understand how development and learning shape the neural networks underlying achievements in literacy, numeracy, and attention. This paper seeks to foster further integration by reviewing the current state of knowledge relating brain changes to behavior and indicating possible future directions. PMID:22912613

Beyond classical inheritance: the influence of maternal genotype upon child's brain morphology and behavior.

PubMed

van der Knaap, Noortje J F; El Marroun, Hanan; Klumpers, Floris; Mous, Sabine E; Jaddoe, Vincent W V; Hofman, Albert; Homberg, Judith R; White, Tonya; Tiemeier, Henning; Fernández, Guillén

2014-07-16

Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior. Copyright © 2014 the authors 0270-6474/14/349516-06$15.00/0.

Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders.

PubMed

Bao, Ai-Min; Swaab, Dick F

2011-04-01

During the intrauterine period a testosterone surge masculinizes the fetal brain, whereas the absence of such a surge results in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other. Sex differences in cognition, gender identity (an individual's perception of their own sexual identity), sexual orientation (heterosexuality, homosexuality or bisexuality), and the risks of developing neuropsychiatric disorders are programmed into our brain during early development. There is no evidence that one's postnatal social environment plays a crucial role in gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with any changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other. Copyright © 2011 Elsevier Inc. All rights reserved.

Early Life Stressors and Genetic Influences on the Development of Bipolar Disorder: The Roles of Childhood Abuse and Brain-Derived Neurotrophic Factor

ERIC Educational Resources Information Center

Liu, Richard T.

2010-01-01

Objectives: Although there is increasing research exploring the psychosocial influences and biological underpinnings of bipolar disorder, relatively few studies have specifically examined the interplay between these factors in the development of this illness. Social-biological models within a developmental psychopathology perspective are necessary…

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice.

PubMed

Alonso, Maria I; Lamus, Francisco; Carnicero, Estela; Moro, Jose A; de la Mano, Anibal; Fernández, Jose M F; Desmond, Mary E; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice

PubMed Central

Alonso, Maria I.; Lamus, Francisco; Carnicero, Estela; Moro, Jose A.; de la Mano, Anibal; Fernández, Jose M. F.; Desmond, Mary E.; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies. PMID:29311854

Prolonged maternal separation disturbs the serotonergic system during early brain development.

PubMed

Ohta, Ken-Ichi; Miki, Takanori; Warita, Katsuhiko; Suzuki, Shingo; Kusaka, Takashi; Yakura, Tomiko; Liu, Jun-Qian; Tamai, Motoki; Takeuchi, Yoshiki

2014-04-01

Early life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time-dependent influence of prolonged maternal separation on male Sprague-Dawley rats. The rats were separated from their dams for 3h twice-daily during postnatal days (PDs) 2-20. The influence of prolonged maternal separation was analyzed on PDs 7, 14, 21, and 28 using HPLC to assess concentrations of serotonin and 5-hydroxyindoleacetic acid and using real-time RT-PCR to measure mRNA expression of the serotonin 1A and 2A receptors in various brain regions. HPLC revealed imbalance between serotonin and 5-hydroxyindoleacetic acid in midbrain raphe nuclei, the amygdala, the hippocampus, and the medial prefrontal cortex (mPFC) on PDs 7 and 14. Furthermore, real-time RT-PCR showed attenuation of mRNA expression of the serotonin 1A receptor in the hippocampus and the mPFC and of the serotonin 2A receptor only in the mPFC on PDs 7 and 14. The observed alterations returned to control levels after maternal separation ended. These findings suggest that the early life stress of prolonged maternal separation disturbs the serotonergic system during a crucial period of brain development, which might in part be responsible for emotional abnormalities later in life. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis.

PubMed

McVey Neufeld, Karen-Anne; Luczynski, Pauline; Dinan, Timothy G; Cryan, John F

2016-04-01

Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult. © The Author(s) 2016.

Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis

PubMed Central

McVey Neufeld, Karen-Anne; Luczynski, Pauline; Dinan, Timothy G.

2016-01-01

Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult. PMID:27254413

The role of sex and gender in neuropsychiatric disorders.

PubMed

Thibaut, Florence

2016-12-01

The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the relationships between brain development and function and sex or gender may help us understand the differences between males and females in terms of risk or resilience factors in brain diseases.

The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

PubMed

Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L

2014-09-12

Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The role of inflammation in perinatal brain injury.

PubMed

Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M; Vannucci, Susan J; Levison, Steven W; Vexler, Zinaida S; Gressens, Pierre

2015-04-01

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals.

The role of inflammation in perinatal brain injury

PubMed Central

Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M.; Vannucci, Susan J.; Levison, Steven W.; Vexler, Zinaida S.; Gressens, Pierre

2015-01-01

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals. PMID:25686754

Sex differences in the gut microbiome-brain axis across the lifespan.

PubMed

Jašarević, Eldin; Morrison, Kathleen E; Bale, Tracy L

2016-02-19

In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome-brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan. © 2016 The Author(s).

A common brain network links development, aging, and vulnerability to disease.

PubMed

Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

2014-12-09

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Development of the blood-brain barrier: a historical point of view.

PubMed

Ribatti, Domenico; Nico, Beatrice; Crivellato, Enrico; Artico, Marco

2006-01-01

Although there has been considerable controversy since the observation by Ehrlich more than 100 years ago that the brain did not take up dyes from the vascular system, the concept of an endothelial blood-brain barrier (BBB) was confirmed by the unequivocal demonstration that the passage of molecules from blood to brain and vice versa was prevented by endothelial tight junctions (TJs). There are three major functions implicated in the term "BBB": protection of the brain from the blood milieu, selective transport, and metabolism or modification of blood- or brain-borne substances. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of complex TJs and a number of specific transport and enzyme systems that regulate molecular traffic across the endothelial cells. The development of the BBB is a complex process that leads to endothelial cells with unique permeability characteristics due to high electrical resistance and the expression of specific transporters and metabolic pathways. This review article summarizes the historical background underlying our current knowledge of the cellular and molecular mechanisms involved in the development and maintenance of the BBB. (c) 2006 Wiley-Liss, Inc.

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

PubMed

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

2016-11-01

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

Micro- and nano-technologies to probe the mechano-biology of the brain.

PubMed

Tay, Andy; Schweizer, Felix E; Di Carlo, Dino

2016-05-24

Biomechanical forces have been demonstrated to influence a plethora of neuronal functions across scales including gene expression, mechano-sensitive ion channels, neurite outgrowth and folding of the cortices in the brain. However, the detailed roles biomechanical forces may play in brain development and disorders has seen limited study, partly due to a lack of effective methods to probe the mechano-biology of the brain. Current techniques to apply biomechanical forces on neurons often suffer from low throughput and poor spatiotemporal resolution. On the other hand, newly developed micro- and nano-technologies can overcome these aforementioned limitations and offer advantages such as lower cost and possibility of non-invasive control of neuronal circuits. This review compares the range of conventional, micro- and nano-technological techniques that have been developed and how they have been or can be used to understand the effect of biomechanical forces on neuronal development and homeostasis.

The impact of junk foods on the adolescent brain.

PubMed

Reichelt, Amy C; Rank, Michelle M

2017-12-01

Adolescence is a significant period of physical, social, and emotional development, and is characterized by prominent neurobiological changes in the brain. The maturational processes that occur in brain regions responsible for cognitive control and reward seeking may underpin excessive consumption of palatable high fat and high sugar "junk" foods during adolescence. Recent studies have highlighted the negative impact of these foods on brain function, resulting in cognitive impairments and altered reward processing. The increased neuroplasticity during adolescence may render the brain vulnerable to the negative effects of these foods on cognition and behavior. In this review, we describe the mechanisms by which junk food diets influence neurodevelopment during adolescence. Diet can lead to alterations in dopamine-mediated reward signaling, and inhibitory neurotransmission controlled by γ-aminobutyric acid (GABA), two major neurotransmitter systems that are under construction across adolescence. We propose that poor dietary choices may derail the normal adolescent maturation process and influence neurodevelopmental trajectories, which can predispose individuals to dysregulated eating and impulsive behaviors. © 2017 Wiley Periodicals, Inc.

Microstructural and functional connectivity in the developing preterm brain

PubMed Central

Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Constable, R. Todd; Ment, Laura R.

2011-01-01

Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity. PMID:21255705

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

PubMed Central

Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

2013-01-01

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

The isoform A of reticulon-4 (Nogo-A) in cerebrospinal fluid of primary brain tumor patients: influencing factors.

PubMed

Koper, Olga Martyna; Kamińska, Joanna; Milewska, Anna; Sawicki, Karol; Mariak, Zenon; Kemona, Halina; Matowicka-Karna, Joanna

2018-05-18

The influence of isoform A of reticulon-4 (Nogo-A), also known as neurite outgrowth inhibitor, on primary brain tumor development was reported. Therefore the aim was the evaluation of Nogo-A concentrations in cerebrospinal fluid (CSF) and serum of brain tumor patients compared with non-tumoral individuals. All serum results, except for two cases, obtained both in brain tumors and non-tumoral individuals, were below the lower limit of ELISA detection. Cerebrospinal fluid Nogo-A concentrations were significantly lower in primary brain tumor patients compared to non-tumoral individuals. The univariate linear regression analysis found that if white blood cell count increases by 1 × 10 3 /μL, the mean cerebrospinal fluid Nogo-A concentration value decreases 1.12 times. In the model of multiple linear regression analysis predictor variables influencing cerebrospinal fluid Nogo-A concentrations included: diagnosis, sex, and sodium level. The mean cerebrospinal fluid Nogo-A concentration value was 1.9 times higher for women in comparison to men. In the astrocytic brain tumor group higher sodium level occurs with lower cerebrospinal fluid Nogo-A concentrations. We found the opposite situation in non-tumoral individuals. Univariate linear regression analysis revealed, that cerebrospinal fluid Nogo-A concentrations change in relation to white blood cell count. In the created model of multiple linear regression analysis we found, that within predictor variables influencing CSF Nogo-A concentrations were diagnosis, sex, and sodium level. Results may be relevant to the search for cerebrospinal fluid biomarkers and potential therapeutic targets in primary brain tumor patients. Nogo-A concentrations were tested by means of enzyme-linked immunosorbent assay (ELISA).

Gender Matters in Elementary Education: Research-Based Strategies to Meet the Distinctive Learning Needs of Boys and Girls

ERIC Educational Resources Information Center

Bonomo, Virginia

2010-01-01

Research indicates that gender influences how children learn. Those findings do not necessarily mean that boys learn one way and girls another. Still, there are significant differences with respect to gender and how our brains develop. Researchers have found that no single area of development influences those gender differences: rather, a…

A review on neuroimaging studies of genetic and environmental influences on early brain development.

PubMed

Gao, Wei; Grewen, Karen; Knickmeyer, Rebecca C; Qiu, Anqi; Salzwedel, Andrew; Lin, Weili; Gilmore, John H

2018-04-16

The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

Biofidelic white matter heterogeneity decreases computational model predictions of white matter strains during rapid head rotations.

PubMed

Maltese, Matthew R; Margulies, Susan S

2016-11-01

The finite element (FE) brain model is used increasingly as a design tool for developing technology to mitigate traumatic brain injury. We developed an ultra high-definition FE brain model (>4 million elements) from CT and MRI scans of a 2-month-old pre-adolescent piglet brain, and simulated rapid head rotations. Strain distributions in the thalamus, coronal radiata, corpus callosum, cerebral cortex gray matter, brainstem and cerebellum were evaluated to determine the influence of employing homogeneous brain moduli, or distinct experimentally derived gray and white matter property representations, where some white matter regions are stiffer and others less stiff than gray matter. We find that constitutive heterogeneity significantly lowers white matter deformations in all regions compared with homogeneous properties, and should be incorporated in FE model injury prediction.

Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

PubMed

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

The influence of acceleration loading curve characteristics on traumatic brain injury.

PubMed

Post, Andrew; Blaine Hoshizaki, T; Gilchrist, Michael D; Brien, Susan; Cusimano, Michael D; Marshall, Shawn

2014-03-21

To prevent brain trauma, understanding the mechanism of injury is essential. Once the mechanism of brain injury has been identified, prevention technologies could then be developed to aid in their prevention. The incidence of brain injury is linked to how the kinematics of a brain injury event affects the internal structures of the brain. As a result it is essential that an attempt be made to describe how the characteristics of the linear and rotational acceleration influence specific traumatic brain injury lesions. As a result, the purpose of this study was to examine the influence of the characteristics of linear and rotational acceleration pulses and how they account for the variance in predicting the outcome of TBI lesions, namely contusion, subdural hematoma (SDH), subarachnoid hemorrhage (SAH), and epidural hematoma (EDH) using a principal components analysis (PCA). Monorail impacts were conducted which simulated falls which caused the TBI lesions. From these reconstructions, the characteristics of the linear and rotational acceleration were determined and used for a PCA analysis. The results indicated that peak resultant acceleration variables did not account for any of the variance in predicting TBI lesions. The majority of the variance was accounted for by duration of the resultant and component linear and rotational acceleration. In addition, the components of linear and rotational acceleration characteristics on the x, y, and z axes accounted for the majority of the remainder of the variance after duration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Critical Periods of Brain Growth and Cognitive Function in Children

ERIC Educational Resources Information Center

Gale, Catharine R.; O'Callaghan, Finbar J.; Godfrey, Keith M.; Law, Catherine M.; Martyn, Christopher N.

2004-01-01

There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We…

Differential Fairness Decisions and Brain Responses after Expressed Emotions of Others in Boys with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Klapwijk, Eduard T.; Aghajani, Moji; Lelieveld, Gert-Jan; van Lang, Natasja D. J.; Popma, Arne; van der Wee, Nic J. A.; Colins, Olivier F.; Vermeiren, Robert R. J. M.

2017-01-01

Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD…

Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries

ERIC Educational Resources Information Center

Driver, Simon

2008-01-01

The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study.

PubMed

Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-04-27

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. Copyright © 2016 the authors 0270-6474/16/364772-14$15.00/0.

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

PubMed Central

Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-01-01

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. PMID:27122035

The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

PubMed

Builee, T L; Hatherill, J R

2004-11-01

Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

Vitamins and neural and cognitive developmental outcomes in children.

PubMed

Benton, David

2012-02-01

The role of vitamin status in the development of the brain and the subsequent functioning of the brain was considered. There are data with a range of vitamins, from animal studies and human studies in developing countries, suggesting that a clinical deficiency during the critical period when the brain is developing causes permanent damage. To date there is, however, with the exception of cases of clinical deficiency such as those that might be associated with a vegan diet, little evidence that variations in the diet of those living in industrialised countries have a lasting developmental influence. Similarly, later in life clinical deficiencies of various vitamins disrupt cognition although there is to date limited evidence that variations in the intake of single vitamins in industrialised societies influence functioning. It may well be, however, unreasonable to expect that vitamins examined in isolation will be associated with differences in cognitive functioning. The output of the brain reflects millions of metabolic processes, each potentially susceptible to any of a range of vitamins. A diet poor in one respect is likely to be poor in other respects as well. As such, the preliminary reports in double-blind placebo-controlled trials that aspects of cognition and behaviour respond to supplementation with multi-micronutrients may indicate the way forward.

Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior

PubMed Central

Skinner, Michael K.; Anway, Matthew D.; Savenkova, Marina I.; Gore, Andrea C.; Crews, David

2008-01-01

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease. PMID:19015723

Friends with social benefits: host-microbe interactions as a driver of brain evolution and development?

PubMed Central

Stilling, Roman M.; Bordenstein, Seth R.; Dinan, Timothy G.; Cryan, John F.

2014-01-01

The tight association of the human body with trillions of colonizing microbes that we observe today is the result of a long evolutionary history. Only very recently have we started to understand how this symbiosis also affects brain function and behavior. In this hypothesis and theory article, we propose how host-microbe associations potentially influenced mammalian brain evolution and development. In particular, we explore the integration of human brain development with evolution, symbiosis, and RNA biology, which together represent a “social triangle” that drives human social behavior and cognition. We argue that, in order to understand how inter-kingdom communication can affect brain adaptation and plasticity, it is inevitable to consider epigenetic mechanisms as important mediators of genome-microbiome interactions on an individual as well as a transgenerational time scale. Finally, we unite these interpretations with the hologenome theory of evolution. Taken together, we propose a tighter integration of neuroscience fields with host-associated microbiology by taking an evolutionary perspective. PMID:25401092

Implications of Prenatal Steroid Perturbations for Neurodevelopment, Behavior, and Autism

PubMed Central

Martien, Katherine M.; Gagnidze, Khatuna; Pfaff, Donald

2014-01-01

The prenatal brain develops under the influence of an ever-changing hormonal milieu that includes endogenous fetal gonadal and adrenal hormones, placental and maternal hormones, and exogenous substances with hormonal activity that can cross the placental barrier. This review discusses the influences of endogenous fetal and maternal hormones on normal brain development and potential consequences of pathophysiological hormonal perturbations to the developing brain, with particular reference to autism. We also consider the effects of hormonal pharmaceuticals used for assisted reproduction, the maintenance of pregnancy, the prevention of congenital adrenal hypertrophy, and hormonal contraceptives continued into an unanticipated pregnancy, among others. These treatments, although in some instances life-saving, may have unintended consequences on the developing fetuses. Additional concern is raised by fetal exposures to endocrine-disrupting chemicals encountered universally by pregnant women from food/water containers, contaminated food, household chemicals, and other sources. What are the potential outcomes of prenatal steroid perturbations on neurodevelopmental and behavioral disorders, including autism-spectrum disorders? Our purposes here are 1) to summarize some consequences of steroid exposures during pregnancy for the development of brain and behavior in the offspring; 2) to summarize what is known about the relationships between exposures and behavior, including autism spectrum disorders; 3) to discuss the molecular underpinnings of such effects, especially molecular epigenetic mechanisms of prenatal steroid manipulations, a field that may explain effects of direct exposures, and even transgenerational effects; and 4) for all of these, to add cautionary notes about their interpretation in the name of scientific rigor. PMID:25211453

Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism.

PubMed

Gore, Andrea C; Martien, Katherine M; Gagnidze, Khatuna; Pfaff, Donald

2014-12-01

The prenatal brain develops under the influence of an ever-changing hormonal milieu that includes endogenous fetal gonadal and adrenal hormones, placental and maternal hormones, and exogenous substances with hormonal activity that can cross the placental barrier. This review discusses the influences of endogenous fetal and maternal hormones on normal brain development and potential consequences of pathophysiological hormonal perturbations to the developing brain, with particular reference to autism. We also consider the effects of hormonal pharmaceuticals used for assisted reproduction, the maintenance of pregnancy, the prevention of congenital adrenal hypertrophy, and hormonal contraceptives continued into an unanticipated pregnancy, among others. These treatments, although in some instances life-saving, may have unintended consequences on the developing fetuses. Additional concern is raised by fetal exposures to endocrine-disrupting chemicals encountered universally by pregnant women from food/water containers, contaminated food, household chemicals, and other sources. What are the potential outcomes of prenatal steroid perturbations on neurodevelopmental and behavioral disorders, including autism-spectrum disorders? Our purposes here are 1) to summarize some consequences of steroid exposures during pregnancy for the development of brain and behavior in the offspring; 2) to summarize what is known about the relationships between exposures and behavior, including autism spectrum disorders; 3) to discuss the molecular underpinnings of such effects, especially molecular epigenetic mechanisms of prenatal steroid manipulations, a field that may explain effects of direct exposures, and even transgenerational effects; and 4) for all of these, to add cautionary notes about their interpretation in the name of scientific rigor.

Reading skill and structural brain development

PubMed Central

Houston, S.M.; Lebel, C.; Katzir, T.; Manis, F.R.; Kan, E.; Rodriguez, G.R.; Sowell, E.R.

2014-01-01

Reading is a learned skill that is likely influenced by both brain maturation and experience. Functional imaging studies have identified brain regions important for skilled reading, but the structural brain changes that co-occur with reading acquisition remain largely unknown. We investigated maturational volume changes in brain reading regions and their association with performance on reading measures. Sixteen typically developing children (5-15 years old, 8 male, mean age of sample=10.06 ±3.29) received two magnetic resonance imaging (MRI) scans, (mean inter-scan interval =2.19 years), and were administered a battery of cognitive measures. Volume changes between time points in five bilateral cortical regions of interest were measured, and assessed for relationships to three measures of reading. Better baseline performances on measures of word reading, fluency and rapid naming, independent of age and total cortical gray matter volume change, were associated with volume decrease in the left inferior parietal cortex. Better baseline performance on a rapid naming measure was associated with volume decrease in the left inferior frontal region. These results suggest that children who are better readers, and who perhaps read more than less skilled readers, exhibit different development trajectories in brain reading regions. Understanding relationships between reading performance, reading experience and brain maturation trajectories may help with the development and evaluation of targeted interventions. PMID:24407200

Two-hit exposure to polychlorinated biphenyls at gestational and juvenile life stages: 2. Sex-specific neuromolecular effects in the brain

PubMed Central

Bell, Margaret R.; Hart, Bethany G.; Gore, Andrea C.

2015-01-01

Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments. PMID:26620572

Severe Urban Outdoor Air Pollution and Children's Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action.

PubMed

D'Angiulli, Amedeo

2018-01-01

According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development.

Severe Urban Outdoor Air Pollution and Children’s Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action

PubMed Central

D’Angiulli, Amedeo

2018-01-01

According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development. PMID:29670873

Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

PubMed Central

Badhan, Raj K. Singh; Chenel, Marylore; Penny, Jeffrey I.

2014-01-01

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways. PMID:24647103

Neonatal handling alters brain organization but does not influence recovery from perinatal cortical injury.

PubMed

Gibb, Robbin; Kolb, Bryan

2005-10-01

Handling rat pups by removing them from the nest during the preweaning period has been shown to influence brain and behavioral development. The authors hypothesized that handling rats with perinatal (Day 4) medial frontal cortex removals might attenuate behavioral deficits and reverse dendritic atrophy associated with such an injury. On the day after surgery, pups were removed from the nest for 15 min, 3 times per day until weaning. Animals were tested as adults in the Morris water task and on skilled reaching. Handled animals showed no improvement in behavioral performance. The handling procedure led to a decrease in dendritic length in parietal cortex, but spine density was unchanged. No therapeutic advantage was observed following the preweaning handling of brain-injured rats.

Microglia: new roles for the synaptic stripper.

PubMed

Kettenmann, Helmut; Kirchhoff, Frank; Verkhratsky, Alexei

2013-01-09

Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered "resting," but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed "synaptic stripping." Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor. Copyright © 2013 Elsevier Inc. All rights reserved.

White Matter Maturation Supports the Development of Reasoning Ability through Its Influence on Processing Speed

ERIC Educational Resources Information Center

Ferrer, Emilio; Whitaker, Kirstie J.; Steele, Joel S.; Green, Chloe T.; Wendelken, Carter; Bunge, Silvia A.

2013-01-01

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes…

Adolescent Neurobiological Susceptibility to Social Context

PubMed Central

Schriber, Roberta A.; Guyer, Amanda E.

2016-01-01

Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

Total Environment Assessment of Stressors Associated with Cognitive Development - A Meta Analysis

EPA Science Inventory

Cognitive development (COGDEV) is marked by a number of critical periods during early childhood in which brain development is influenced by myriad chemical and non-chemical stressors from the built, natural, and social environments. Inherent factors and behaviors can also directl...

Epigenetic Influences on Brain Development and Plasticity

PubMed Central

Fagiolini, Michela; Jensen, Catherine L.; Champagne, Frances A.

2009-01-01

A fine interplay exists between sensory experience and innate genetic programs leading to the sculpting of neuronal circuits during early brain development. Recent evidence suggests that the dynamic regulation of gene expression through epigenetic mechanisms is at the interface between environmental stimuli and long-lasting molecular, cellular and complex behavioral phenotypes acquired during periods of developmental plasticity. Understanding these mechanisms may give insight into the formation of critical periods and provide new strategies for increasing plasticity and adaptive change in adulthood. PMID:19545993

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings.

PubMed

Bralten, Janita; Greven, Corina U; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P; Rommelse, Nanda N J; Hartman, Catharina; van der Meer, Dennis; O'Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2016-06-01

Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research.

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

PubMed Central

Bralten, Janita; Greven, Corina U.; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P.; Rommelse, Nanda N.J.; Hartman, Catharina; van der Meer, Dennis; O’Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J.; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K.

2016-01-01

Background Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8–30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research. PMID:26679925

The influence of meteorological and geomagnetic factors on acute myocardial infarction and brain stroke in Moscow, Russia.

PubMed

Shaposhnikov, Dmitry; Revich, Boris; Gurfinkel, Yuri; Naumova, Elena

2014-07-01

Evidence of the impact of air temperature and pressure on cardiovascular morbidity is still quite limited and controversial, and even less is known about the potential influence of geomagnetic activity. The objective of this study was to assess impacts of air temperature, barometric pressure and geomagnetic activity on hospitalizations with myocardial infarctions and brain strokes. We studied 2,833 myocardial infarctions and 1,096 brain strokes registered in two Moscow hospitals between 1992 and 2005. Daily event rates were linked with meteorological and geomagnetic conditions, using generalized linear model with controls for day of the week, seasonal and long-term trends. The number of myocardial infarctions decreased with temperature, displayed a U-shaped relationship with pressure and variations in pressure, and increased with geomagnetic activity. The number of strokes increased with temperature, daily temperature range and geomagnetic activity. Detrimental effects on strokes of low pressure and falling pressure were observed. Relative risks of infarctions and strokes during geomagnetic storms were 1.29 (95% CI 1.19-1.40) and 1.25 (1.10-1.42), respectively. The number of strokes doubled during cold spells. The influence of barometric pressure on hospitalizations was relatively greater than the influence of geomagnetic activity, and the influence of temperature was greater than the influence of pressure. Brain strokes were more sensitive to inclement weather than myocardial infarctions. This paper provides quantitative estimates of the expected increases in hospital admissions on the worst days and can help to develop preventive health plans for cardiovascular diseases.

Loss of T cells influences sex differences in behavior and brain structure.

PubMed

Rilett, Kelly C; Friedel, Miriam; Ellegood, Jacob; MacKenzie, Robyn N; Lerch, Jason P; Foster, Jane A

2015-05-01

Clinical and animal studies demonstrate that immune-brain communication influences behavior and brain function. Mice lacking T cell receptor β and δ chains were tested in the elevated plus maze, open field, and light-dark test and showed reduced anxiety-like behavior compared to wild type. Interestingly sex differences were observed in the behavioural phenotype of TCRβ-/-δ- mice. Specifically, female TCRβ-/-δ- mice spent more time in the light chamber compared to wild type females, whereas male TCRβ-/-δ- spent more time in the center of the open field compared to wild type males. In addition, TCRβ-/-δ- mice did not show sex differences in activity-related behaviors observed in WT mice. Ex vivo brain imaging (7 Tesla MRI) revealed volume changes in hippocampus, hypothalamus, amygdala, periaqueductal gray, and dorsal raphe and other brain regions between wild type and T cell receptor knockout mice. There was also a loss of sexual dimorphism in brain volume in the bed nucleus of the stria terminalis, normally the most sexually dimorphic region in the brain, in immune compromised mice. These data demonstrate the presence of T cells is important in the development of sex differences in CNS circuitry and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Nutritional strategies to optimise cognitive function in the aging brain.

PubMed

Wahl, Devin; Cogger, Victoria C; Solon-Biet, Samantha M; Waern, Rosilene V R; Gokarn, Rahul; Pulpitel, Tamara; Cabo, Rafael de; Mattson, Mark P; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

2016-11-01

Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low-protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. Copyright © 2016 Elsevier B.V. All rights reserved.

Teaching About “Brain and Learning” in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence

PubMed Central

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about “Brain and Learning” using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in “Brain and Learning” and 1241 students in grades 8–9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of “Brain and Learning” had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into “Brain and Learning,” and for changing students' beliefs about intelligence. PMID:26648900

Influences of brain development and ageing on cortical interactive networks.

PubMed

Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

2011-02-01

To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

PubMed

Banks, William A; Abrass, Christine K; Hansen, Kim M

2016-01-01

Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health.

PubMed

Raichlen, David A; Alexander, Gene E

2017-07-01

The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise-brain connections are not well understood. We use an evolutionary neuroscience approach to develop the adaptive capacity model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: (i) what are the proximate and ultimate mechanisms underlying age-related brain atrophy, and (ii) how do lifestyle changes influence the trajectory of healthy and pathological aging? Copyright © 2017 Elsevier Ltd. All rights reserved.

Action Research: How Children in the Fifth Grade Spend Their Time Outside of School.

ERIC Educational Resources Information Center

Wells, Lauren; Blendinger, Jack

Neurological research indicates that children's experiences, both inside and outside of school, significantly influence brain development. But little is known about children's out-of-school activities and the influence such activities may have on academic achievement. To better understand this relationship, the extra-school activities of 75…

Sex Influences on the Neurobiology of Learning and Memory

ERIC Educational Resources Information Center

Andreano, Joseph M.; Cahill, Larry

2009-01-01

In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an…

Proceedings of the 2017 annual meeting of the Fetal Alcohol Spectrum Disorders study group.

PubMed

Wozniak, Jeffrey R; Klintsova, Anna Y; Hamilton, Derek A; Mooney, Sandra M

2018-06-01

The 2017 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled "Prenatal alcohol exposure in the context of multiple factors affecting brain development." The theme was reflected in the interactions between members of the Teratology Society and the FASDSG this year. The first keynote speaker, Elaine Faustman, Ph.D., was a liaison between the societies and spoke about systems biology and the multiple genetic and environmental influences on development. The second keynote speaker, Rebecca Knickmeyer, Ph.D., discussed population neuroscience and multiple influences on brain development. The conference presented updates from three government agencies and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by Dr. John Hannigan, Ph.D., the recipient of the 2017 Henry Rosett award for career-long contributions to the field. Copyright © 2017 Elsevier Inc. All rights reserved.

A half-truth is a whole lie: on the necessity of investigating sex influences on the brain.

PubMed

Cahill, Larry

2012-06-01

Sex influences are proving to be extremely widespread on brain function, including the human brain. Ample evidence now proves that the sex of subjects can influence, ever reverse, findings, hence conclusions, at all levels of brain science, down to the molecular level, often in completely unanticipated ways. Thus the still-prominent assumption that sex influences may be safely ignored by neurobiologists is invalid and must be abandoned. The failure to properly consider the issue fills the literature with conclusions tenuous at best, false at worst. The continuing, widespread resistance to investigating sex influences among brain scientists, a resistance largely rooted in deeply entrenched biases against the topic, is becoming increasingly scientifically indefensible and strongly retards progress in our field.

Fetal Neurobehavioral Development and the Role of Maternal Nutrient Intake and Psychological Health

ERIC Educational Resources Information Center

Spann, Marisa; Smerling, Jennifer; Gustafsson, Hanna C.; Foss, Sophie; Monk, Catherine

2014-01-01

Measuring and understanding fetal neurodevelopment provides insight regarding the developing brain. Maternal nutrient intake and psychological stress during pregnancy each impact fetal neurodevelopment and influence childhood outcomes and are thus important factors to consider when studying fetal neurobehavioral development. The authors provide an…

Influence of Inflammation on Poststroke Plasticity

PubMed Central

Kossut, Malgorzata

2013-01-01

Age-related brain injuries including stroke are a leading cause of morbidity and mental disability worldwide. Most patients who survive stroke experience some degree of recovery. The restoration of lost functions can be explained by neuronal plasticity, understood as brain ability to reorganize and remodel itself in response to changed environmental requirements. However, stroke triggers a cascade of events which may prevent the normal development of the plastic changes. One of them may be inflammatory response initiated immediately after stroke, which has been found to contribute to neuronal injury. Some recent evidence though has suggested that inflammatory reaction can be also neuroprotective. This paper attempts to discuss the influence of poststroke inflammatory response on brain plasticity and stroke outcome. We also describe the recent anti-inflammatory strategies that have been effective for recovery in experimental stroke. PMID:23533818

Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

PubMed

O'Mahony, S M; Clarke, G; Borre, Y E; Dinan, T G; Cryan, J F

2015-01-15

The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of altered gravity on brain cellular energy and plasma membrane metabolism of developing lower aquatic vertebrates

NASA Astrophysics Data System (ADS)

Slenzka, K.; Appel, R.; Kappel, Th.; Rahmann, H.

Biochemical analyses of the brain of cichlid fish larvae, exposed for 7 days to increased acceleration of 3g (hyper-g), revealed an increase in energy availability (succinate dehydrogenase activity, SDH), and in mitochondrial energy transformation (creatine kinase, Mi_a-CK), but no changes in an energy consumptive process (high-affinity Ca^2+-ATPase). Brain glucose-6-phosphate dehydrogenase (G6PDH) of developing fish was previously found to be increased after hyper-g exposure. Three respectively 5 hours thereafter dramatic fluctuations in enzyme activity were registered. Analysing the cytosolic or plasma membrane-located brain creatine kinase (BB-CK) of clawed toad larvae after long-term hyper-g exposure a significant increase in enzyme activity was demonstrated, whereas the activity of a high affinity Ca^2+-ATPase remained unaffected.

Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids

PubMed Central

Kellogg, Carol K.; Kenjarski, Thomas P.; Pleger, Gloria L.; Frye, Cheryl A.

2013-01-01

Fetal exposure to diazepam (DZ), a positive modulator of GABAA receptors and an agonist at mitochondrial benzodiazine receptors, induces long-term neural and behavioral effects. This study evaluated whether the early manipulation influenced the normal development of brain levels of neurosteroids or altered steroid action at GABAA receptors. Pregnant dams were injected over gestation days 14 through 20 with DZ (2.5 mg/kg) or the vehicle. Male and female offspring were analyzed at five postnatal ages. The levels of progesterone (P), dihydroprogesterone (DHP), 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), testosterone (T), dihydrotestosterone, and 5α-androstan-3α,17β diol were measured in the cerebral cortex and diencephalon. The results indicated that development of brain steroid levels and the impact of fetal DZ exposure were region- and sex-specific. Age-related changes in brain steroids did not mirror associated changes in circulating P and T. Age regulated the levels of all 3 progestins in the cerebral cortex, and fetal DZ exposure interacted with the development of P and DHP. The development of 3α,5α-THP in the cortex was markedly influenced by sex, with levels in males decreasing over postnatal development whereas they increased over postpubertal development in females. An adolescent surge in T levels was observed in male cortex and fetal DZ exposure prevented that surge. Steroid levels in the diencephalon were altered by age mainly in females, and DZ exposure had little effect in this region. The data support region-specific regulation of brain steroid synthesis. Only in the cerebral cortex are relevant mechanisms readily modifiable by fetal DZ exposure. However, neither sex nor fetal DZ exposure altered the response of GABAA receptors in adult cortex to neurosteroid. PMID:16376310

NEUROBEHAVIORAL EFFECTS OF GESTATIONAL AND PERINATAL EXPOSURE TO HEPTACHLOR IN RATS.

EPA Science Inventory

In nervous system development, GABA serves as a trophic signal which influences the development of almost all neurotransmitter systems, and is the earliest neurotransmitter detected in fetal rat brain. Since cyclodiene pesticides block GABAergic neurotransmission they may have pr...

CNS development: an overview

NASA Technical Reports Server (NTRS)

Nowakowski, R. S.; Hayes, N. L.

1999-01-01

The basic principles of the development of the central nervous system (CNS) are reviewed, and their implications for both normal and abnormal development of the brain are discussed. The goals of this review are (a) to provide a set of concepts to aid in understanding the variety of complex processes that occur during CNS development, (b) to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and (c) to provide a basis for understanding how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

Biological, developmental, and neurobehavioral factors relevant to adolescent driving risks.

PubMed

Dahl, Ronald E

2008-09-01

This article reviews emerging knowledge about key aspects of neurobehavioral development, with an emphasis on the development of self-regulation over behavior and emotions and its relevance to driving risks among youth. It begins with a brief overview of recent advances in understanding adolescent brain maturation and presents a heuristic model focusing on brain-behavior-social-context interactions during adolescent development. The article considers the relatively slow neurobehavioral maturation of cognitive control and emphasizes the importance of affective influences on decision making. It points to several questions about programs and policies that may help to protect high-risk youth during this important maturational period. The heuristic model is then used to examine a specific neuroregulatory system during adolescence--the regulation of sleep and arousal. This focus on sleep illustrates key points about brain-behavior-social-context interactions by looking at both biological and social influences on sleep in teens. Moreover, sleep has direct relevance to understanding a specific dimension of driving risk in youth. Sleep deprivation is rampant among adolescents, and the consequences of insufficient sleep (sleepiness, lapses in attention, susceptibility to aggression, and negative synergy with alcohol) appear to contribute significantly to driving risks in teens.

The intersection of stress, drug abuse and development.

PubMed

Thadani, Pushpa V

2002-01-01

Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

PubMed Central

Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

2015-01-01

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

Zinc in gut-brain interaction in autism and neurological disorders.

PubMed

Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M

2015-01-01

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

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

Moreira, Estefania G.; Department of Physiological Sciences, State University of Londrina, Londrina, PR; Yu Xiaozhong

2010-06-15

Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles acrossmore » doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.« less

Gender development and the human brain.

PubMed

Hines, Melissa

2011-01-01

Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

Association of Child Poverty, Brain Development, and Academic Achievement.

PubMed

Hair, Nicole L; Hanson, Jamie L; Wolfe, Barbara L; Pollak, Seth D

2015-09-01

Children living in poverty generally perform poorly in school, with markedly lower standardized test scores and lower educational attainment. The longer children live in poverty, the greater their academic deficits. These patterns persist to adulthood, contributing to lifetime-reduced occupational attainment. To determine whether atypical patterns of structural brain development mediate the relationship between household poverty and impaired academic performance. Longitudinal cohort study analyzing 823 magnetic resonance imaging scans of 389 typically developing children and adolescents aged 4 to 22 years from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development with complete sociodemographic and neuroimaging data. Data collection began in November 2001 and ended in August 2007. Participants were screened for a variety of factors suspected to adversely affect brain development, recruited at 6 data collection sites across the United States, assessed at baseline, and followed up at 24-month intervals for a total of 3 periods. Each study center used community-based sampling to reflect regional and overall US demographics of income, race, and ethnicity based on the US Department of Housing and Urban Development definitions of area income. One-quarter of sample households reported the total family income below 200% of the federal poverty level. Repeated observations were available for 301 participants. Household poverty measured by family income and adjusted for family size as a percentage of the federal poverty level. Children's scores on cognitive and academic achievement assessments and brain tissue, including gray matter of the total brain, frontal lobe, temporal lobe, and hippocampus. Poverty is tied to structural differences in several areas of the brain associated with school readiness skills, with the largest influence observed among children from the poorest households. Regional gray matter volumes of children below 1.5 times the federal poverty level were 3 to 4 percentage points below the developmental norm (P < .05). A larger gap of 8 to 10 percentage points was observed for children below the federal poverty level (P < .05). These developmental differences had consequences for children's academic achievement. On average, children from low-income households scored 4 to 7 points lower on standardized tests (P < .05). As much as 20% of the gap in test scores could be explained by maturational lags in the frontal and temporal lobes. The influence of poverty on children's learning and achievement is mediated by structural brain development. To avoid long-term costs of impaired academic functioning, households below 150% of the federal poverty level should be targeted for additional resources aimed at remediating early childhood environments.

Toward a physical basis of attention and self-regulation

NASA Astrophysics Data System (ADS)

Posner, Michael I.; Rothbart, Mary K.

2009-06-01

The concept of self-regulation is central to the understanding of human development. Self-regulation allows effective socialization and predicts both psychological pathologies and levels of achievement in schools. What has been missing are neural mechanisms to provide understanding of the cellular and molecular basis for self-regulation. We show that self-regulation can be measured during childhood by parental reports and by self-reports of adolescents and adults. These reports are summarized by a higher order factor called effortful control, which reflects perceptions about the ability of a given person to regulate their behavior in accord with cultural norms. Throughout childhood effortful control is related to children's performance in computerized conflict related tasks. Conflict tasks have been shown in neuroimaging studies to activate specific brain networks of executive attention. Several brain areas work together at rest and during cognitive tasks to regulate competing brain activity and thus control resulting behavior. The cellular structure of the anterior cingulate and insula contain cells, unique to humans and higher primates that provide strong links to remote brain areas. During conflict tasks, anterior cingulate activity is correlated with activity in remote sensory and emotional systems, depending upon the information selected for the task. During adolescence the structure and activity of the anterior cingulate has been found to be correlated with self-reports of effortful control. Studies have provided a perspective on how genes and environment act to shape the executive attention network, providing a physical basis for self-regulation. The anterior cingulate is regulated by dopamine. Genes that influence dopamine levels in the CNS have been shown to influence the efficiency of self-regulation. For example, alleles of the COMT gene that influence the efficiency of dopamine transmission are related to the ability to resolve conflict. Humans with disorders involving deletion of this gene exhibit large deficits in self-regulation. Alleles of other genes influencing dopamine and serotonin transmission have also been found to influence ability to resolve conflict in cognitive tasks. However, as is the case for many genes, the effectiveness of COMT alleles in shaping self-regulation depends upon cultural influences such as parenting. Studies find that aspects of parenting quality and parent training can influence child behavior and the efficiency of self-regulation. During development, the network that relates to self-regulation undergoes important changes in connectivity. Infants can use parts of the self-regulatory network to detect errors in sensory information, but the network does not yet have sufficient connectivity to organize brain activity in a coherent way. During middle childhood, along with increased projection cells involved in remote connections of dorsal anterior cingulate and prefrontal and parietal cortex, executive network connectivity increases and shifts from predominantly short to longer range connections. During this period specific exercises can influence network development and improve self-regulation. Understanding the physical basis of self-regulation has already cast light on individual differences in normal and pathological states and gives promise of allowing the design of methods to improve aspects of human development.

The neonatal brain in critical congenital heart disease: Insights and future directions.

PubMed

Peyvandi, Shabnam; Latal, Beatrice; Miller, Steven P; McQuillen, Patrick S

2018-05-19

Neurodevelopmental outcomes are impaired in survivors of critical congenital heart disease (CHD) in several developmental domains including motor, cognitive and sensory outcomes. These deficits can extend into the adolescent and early adulthood years. The cause of these neurodevelopmental impairments is multi-factorial and includes patient specific risk factors, cardiac anatomy and physiology as well as brain changes seen on MRI. Advances in imaging techniques have identified delayed brain development in the neonate with critical CHD as well as acquired brain injury. These abnormalities are seen even before corrective neonatal cardiac surgery. This review focuses on describing brain changes seen on MRI in neonates with CHD, risk factors for these changes and the association with neurodevelopmental outcome. There is an emerging focus on the impact of cardiovascular physiology on brain health and the complex heart-brain interplay that influences ultimate neurodevelopmental outcome in these patients. Copyright © 2018. Published by Elsevier Inc.

Sexual differentiation of the human brain in relation to gender identity and sexual orientation.

PubMed

Savic, Ivanka; Garcia-Falgueras, Alicia; Swaab, Dick F

2010-01-01

It is believed that during the intrauterine period the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. According to this concept, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation should be programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality. This also means that in the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain. There is no proof that social environment after birth has an effect on gender identity or sexual orientation. Data on genetic and hormone independent influence on gender identity are presently divergent and do not provide convincing information about the underlying etiology. To what extent fetal programming may determine sexual orientation is also a matter of discussion. A number of studies show patterns of sex atypical cerebral dimorphism in homosexual subjects. Although the crucial question, namely how such complex functions as sexual orientation and identity are processed in the brain remains unanswered, emerging data point at a key role of specific neuronal circuits involving the hypothalamus. Copyright © 2010 Elsevier B.V. All rights reserved.

Diet and gender influences on processing and discrimination of speech sounds in 3 and 6 month-old infants: A developmental ERP study

USDA-ARS?s Scientific Manuscript database

Although early post-natal nutrition influences later development, there are no studies comparing brain function in healthy infants fed the three major infant diets (breast milk, milk-based and soy-based formula) even though these diets differ significantly in nutrient composition. We have studied br...

Sexual risk-taking and subcortical brain volume in adolescence.

PubMed

Feldstein Ewing, Sarah W; Hudson, Karen A; Caouette, Justin; Mayer, Andrew R; Thayer, Rachel E; Ryman, Sephira G; Bryan, Angela D

2018-04-19

The developmental period of adolescence marks the initiation of new socioemotional and physical behaviors, including sexual intercourse. However, little is known about neurodevelopmental influences on adolescent sexual decision-making. We sought to determine how subcortical brain volume correlated with condom use, and whether those associations differed by gender and pubertal development. We used FreeSurfer to extract subcortical volume among N = 169 sexually experienced youth (mean age 16.07 years; 31.95% female). We conducted multiple linear regressions to examine the relationship between frequency of condom use and subcortical volume, and whether these associations would be moderated by gender and pubertal development. We found that the relationship between brain volume and condom use was better accounted for by pubertal development than by gender, and moderated the association between limbic brain volume and condom use. No significant relationships were observed in reward areas (e.g., nucleus accumbens) or prefrontal cortical control areas. These data highlight the potential relevance of subcortical socioemotional processing structures in adolescents' sexual decision-making.

Social dysfunction after pediatric traumatic brain injury: a translational perspective

PubMed Central

Ryan, Nicholas P.; Catroppa, Cathy; Godfrey, Celia; Noble-Haeusslein, Linda J.; Shultz, Sandy R.; O'Brien, Terence J.; Anderson, Vicki; Semple, Bridgette D.

2016-01-01

Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the emergence, development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. PMID:26949224

Children's exposure to violent video games and desensitization to violence.

PubMed

Funk, Jeanne B

2005-07-01

Desensitization to violence is cited frequently as being an outcome of exposure to media violence and a condition that contributes to increased aggression. This article initiates the development of a conceptual model for describing possible relationships among violent video games, brain function, and desensitization by using empathy and attitudes toward violence as proxy measures of desensitization. More work is needed to understand how specific game content may affect brain activity, how brain development may be affected by heavy play at young ages, and how personality and lifestyle variables may moderate game influence. Given the current state of knowledge, recommendations are made for clinicians to help parents monitor and limit exposure to violent video games and encourage critical thinking about media violence.

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

PubMed

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

2014-08-20

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

Endothelial LRP1 - A Potential Target for the Treatment of Alzheimer's Disease : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.

PubMed

Storck, Steffen E; Pietrzik, Claus U

2017-12-01

The accumulation of the neurotoxin beta-amyloid (Aβ) is a major hallmark in Alzheimer's disease (AD). Aβ homeostasis in the brain is governed by its production and various clearance mechanisms. Both pathways are influenced by the ubiquitously expressed low-density lipoprotein receptor-related protein 1 (LRP1). In cerebral blood vessels, LRP1 is an important mediator for the rapid removal of Aβ from brain via transport across the blood-brain barrier (BBB). Here, we summarize recent findings on LRP1 function and discuss the targeting of LRP1 as a modulator for AD pathology and drug delivery into the brain.

Neurodevelopmental origins of lifespan changes in brain and cognition.

PubMed

Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J; Håberg, Asta K; Kremen, William S; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S; Rohani, Darius A; Skranes, Jon; Storsve, Andreas B; Sølsnes, Anne Elisabeth; Tamnes, Christian K; Thompson, Wesley K; Reuter, Chase; Dale, Anders M; Fjell, Anders M

2016-08-16

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

Hygiene and other early childhood influences on the subsequent function of the immune system.

PubMed

Rook, Graham A W; Lowry, Christopher A; Raison, Charles L

2015-08-18

The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The influence of victim characteristics on potential jurors' perceptions of brain damage in mild traumatic brain injury.

PubMed

Guilmette, T J; Temple, R O; Kennedy, M L; Weiler, M D; Ruffolo, L F; Dufresne, E

2005-11-01

To determine the influence of victim/plaintiff sex, occupation and intoxication status at the time of injury on potential jurors' judgement about the presence of brain damage in mild traumatic brain injury (MTBI). Survey. One of eight scenarios describing a MTBI from a motor vehicle accident was presented to 460 participants at a Department of Motor Vehicles. Victim sex, occupation (accountant or cafeteria worker) and alcohol intoxication status at the time of injury (sober or intoxicated) were manipulated across eight scenarios. Participants rated whether the victim's complaints at 6 months post-injury were the result of brain damage. Ratings were influenced by victim occupation and intoxication status (chi2>5.3, p<0.03), but not the sex of the victim. The occupational and intoxication status of MTBI victims may influence potential jurors' decision about the presence of brain damage.

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome*

PubMed Central

Trazzi, Stefania; Fuchs, Claudia; Valli, Emanuele; Perini, Giovanni; Bartesaghi, Renata; Ciani, Elisabetta

2013-01-01

Intellectual disability in Down syndrome (DS) appears to be related to severe proliferation impairment during brain development. Recent evidence shows that it is not only cellular proliferation that is heavily compromised in DS, but also cell fate specification and dendritic maturation. The amyloid precursor protein (APP), a gene that is triplicated in DS, plays a key role in normal brain development by influencing neural precursor cell proliferation, cell fate specification, and neuronal maturation. APP influences these processes via two separate domains, the APP intracellular domain (AICD) and the soluble secreted APP. We recently found that the proliferation impairment of neuronal precursors (NPCs) from the Ts65Dn mouse model for DS was caused by derangement of the Shh pathway due to overexpression of patched1(Ptch1), its inhibitory regulator. Ptch1 overexpression was related to increased levels within the APP/AICD system. The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development. We found that normalization of APP expression restored the reduced neuronogenesis, the increased astrogliogenesis, and the reduced neurite length of trisomic NPCs, indicating that APP overexpression underpins all aspects of neurogenesis impairment. Moreover, we found that two different domains of APP impair neuronal differentiation and maturation in trisomic NPCs. The APP/AICD system regulates neuronogenesis and neurite length through the Shh pathway, whereas the APP/secreted AP system promotes astrogliogenesis through an IL-6-associated signaling cascade. These results provide novel insight into the mechanisms underlying brain development alterations in DS. PMID:23740250

The influence of sex chromosome aneuploidy on brain asymmetry.

PubMed

Rezaie, Roozbeh; Daly, Eileen M; Cutter, William J; Murphy, Declan G M; Robertson, Dene M W; DeLisi, Lynn E; Mackay, Clare E; Barrick, Thomas R; Crow, Timothy J; Roberts, Neil

2009-01-05

The cognitive deficits present in individuals with sex chromosome aneuploidies suggest that hemispheric differentiation of function is determined by an X-Y homologous gene [Crow (1993); Lancet 342:594-598]. In particular, females with Turner's syndrome (TS) who have only one X-chromosome exhibit deficits of spatial ability whereas males with Klinefelter's syndrome (KS) who possess a supernumerary X-chromosome are delayed in acquiring words. Since spatial and verbal abilities are generally associated with right and left hemispheric function, such deficits may relate to anomalies of cerebral asymmetry. We therefore applied a novel image analysis technique to investigate the relationship between sex chromosome dosage and structural brain asymmetry. Specifically, we tested Crow's prediction that the magnitude of the brain torque (i.e., a combination of rightward frontal and leftward occipital asymmetry) would, as a function of sex chromosome dosage, be respectively decreased in TS women and increased in KS men, relative to genotypically normal controls. We found that brain torque was not significantly different in TS women and KS men, in comparison to controls. However, TS women exhibited significantly increased leftward brain asymmetry, restricted to the posterior of the brain and focused on the superior temporal and parietal-occipital association cortex, while KS men showed a trend for decreased brain asymmetry throughout the frontal lobes. The findings suggest that the number of sex chromosomes influences the development of brain asymmetry not simply to modify the torque but in a complex pattern along the antero-posterior axis. 2008 Wiley-Liss, Inc.

Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

PubMed

Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

2018-04-01

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses1

PubMed Central

Kielian, Tammy; Md. Syed, Mohsin; Liu, Shuliang; Phulwani, Nirmal K.; Phillips, Napoleon; Wagoner, Gail; Drew, Paul D.; Esen, Nilufer

2008-01-01

Brain abscesses result from a pyogenic parenchymal infection commonly initiated by Gram-positive bacteria such as Staphylococcus aureus. Although the host immune response elicited following infection is essential for effective bacterial containment, this response also contributes to the significant loss of brain parenchyma by necrosis that may be reduced by modulating the inflammatory response. Ciglitazone, a PPAR-γ agonist with anti-inflammatory properties, was evaluated for its ability to influence the course of brain abscess development when treatment was initiated 3 days following infection. Interestingly, abscess-associated bacterial burdens were significantly lower following ciglitazone administration, which could be explained, in part, by the finding that ciglitazone enhanced S. aureus phagocytosis by microglia. In addition, ciglitazone attenuated the expression of select inflammatory mediators during brain abscess development including inducible NO synthase, TNF-α, IL-1β, CXCL2, and CCL3. Unexpectedly, ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and α-smooth muscle actin-positive myofibroblasts. Collectively, through its ability to attenuate excessive inflammation and accelerate abscess encapsulation, ciglitazone may effectively sequester brain abscesses and limit bacterial dissemination. PMID:18354226

IV. The cognitive implications of obesity and nutrition in childhood.

PubMed

Khan, Naiman A; Raine, Lauren B; Donovan, Sharon M; Hillman, Charles H

2014-12-01

The prevalence of childhood obesity in the United States has tripled since the 1980s and is strongly linked to the early onset of several metabolic diseases. Recent studies indicate that lower cognitive function may be another complication of childhood obesity. This review considers the research to date on the role of obesity and nutrition on childhood cognition and brain health. Although a handful of studies point to a maladaptive relationship between obesity and aspects of cognitive control, remarkably little is known regarding the impact of fat mass on brain development and cognitive function. Further, missing from the literature is the role of nutrition in the obesity-cognition interaction. Nutrition may directly or indirectly influence cognitive performance via several pathways including provision of key substrates for optimal brain health, modulation of gut microbiota, and alterations in systemic energy balance. However, in the absence of malnutrition, the functional benefits of specific nutrient intake on particular cognitive domains are not well characterized. Here, we examine the literature linking childhood obesity and cognition while considering the effects of nutritional intake. Possible mechanisms for these relationships are discussed and suggestions are made for future study topics. Although childhood obesity prevalence rates in some developed countries have recently stabilized, significant disparities remain among groups based on sex and socioeconomic status. Given that the elevated prevalence of pediatric overweight and obesity may persist for the foreseeable future, it is crucial to develop a comprehensive understanding of the influence of obesity and nutrition on cognition and brain health in the pediatric population. © 2014 The Society for Research in Child Development, Inc.

Choline Availability During Embryonic Development Alters Progenitor Cell Mitosis in Developing Mouse Hippocampus1,2

PubMed Central

Craciunescu, Corneliu N.; Albright, Craig D.; Mar, Mei-Heng; Song, Jiannan; Zeisel, Steven H.

2006-01-01

Previously, we reported that dietary choline influences development of the hippocampus in fetal rat brain. It is important to know whether similar effects of choline occur in developing fetal mouse brain because interesting new experimental approaches are now available using several transgenic mouse models. Timed-pregnant mice were fed choline-supplemented (CS), control (CT) or choline-deficient (CD) AIN-76 diet from embryonic day 12 to 17 (E12–17). Fetuses from CD dams had diminished concentrations of phosphocholine and phosphatidylcholine in their brains compared with CT or CS fetuses (P < 0.05). When we analyzed fetal hippocampus on day E17 for cells with mitotic phase–specific expression of phosphorylated histone H3, we detected fewer labeled cells at the ventricular surface of the ventricular zone in the CD group (14.8 ± 1.9) compared with the CT (30.7 ± 1.9) or CS (36.6 ± 2.6) group (P < 0.05). At the same time, we detected more apoptotic cells in E17 hippocampus using morphology in the CD group (11.8 ± 1.4) than in CT (5.6 ± 0.6) or CS (4.2 ± 0.7) group (P < 0.05). This was confirmed using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin anti-digoxigenin fluorescein conjugate antibody nick end-labeling (TUNEL) and activated caspase-3 immunoreactivity. We conclude that the dietary availability of choline to the mouse dam influences progenitor cell proliferation and apoptosis in the fetal brain. J. Nutr. 133: 3614–3618, 2003. PMID:14608083

MicroRNAs in neuronal function and dysfunction

PubMed Central

Im, Heh-In; Kenny, Paul J.

2012-01-01

MicroRNAs (miRNAs) are small noncoding RNA transcripts expressed throughout the brain that can regulate neuronal gene expression at the post-transcriptional level. Here, we provide an overview of the role for miRNAs in brain development and function, and review evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction. A better understanding of how miRNAs influence the development of neuropsychiatric disorders may reveal fundamental insights into the causes of these devastating illnesses and offer novel targets for therapeutic development. PMID:22436491

Pathogenesis of Hepatic Encephalopathy

PubMed Central

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

Genetic Psychophysiology: advances, problems, and future directions

PubMed Central

Anokhin, Andrey P.

2014-01-01

This paper presents an overview of historical advances and the current state of genetic psychophysiology, a rapidly developing interdisciplinary research linking genetics, brain, and human behavior, discusses methodological problems, and outlines future directions of research. The main goals of genetic psychophysiology are to elucidate the neural pathways and mechanisms mediating genetic influences on cognition and emotion, identify intermediate brain-based phenotypes for psychopathology, and provide a functional characterization of genes being discovered by large association studies of behavioral phenotypes. Since the initiation of this neurogenetic approach to human individual differences in the 1970s, numerous twin and family studies have provided strong evidence for heritability of diverse aspects of brain function including resting-state brain oscillations, functional connectivity, and event-related neural activity in a variety of cognitive and emotion processing tasks, as well as peripheral psychophysiological responses. These data indicate large differences in the presence and strength of genetic influences across measures and domains, permitting the selection of heritable characteristics for gene finding studies. More recently, candidate gene association studies began to implicate specific genetic variants in different aspects of neurocognition. However, great caution is needed in pursuing this line of research due to its demonstrated proneness to generate false-positive findings. Recent developments in methods for physiological signal analysis, hemodynamic imaging, and genomic technologies offer new exciting opportunities for the investigation of the interplay between genetic and environmental factors in the development of individual differences in behavior, both normal and abnormal. PMID:24739435

Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases.

PubMed

Lukas, Rimas V; Mehta, Minesh P; Lesniak, Maciej S

2015-06-01

The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Studies investigating the factors that independently influence survival in participants with brain metastases are presented. The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non-small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

An imaging genetics approach to understanding social influence

PubMed Central

Falk, Emily B.; Way, Baldwin M.; Jasinska, Agnes J.

2012-01-01

Normative social influences shape nearly every aspect of our lives, yet the biological processes mediating the impact of these social influences on behavior remain incompletely understood. In this Hypothesis, we outline a theoretical framework and an integrative research approach to the study of social influences on the brain and genetic moderators of such effects. First, we review neuroimaging evidence linking social influence and conformity to the brain's reward system. We next review neuroimaging evidence linking social punishment (exclusion) to brain systems involved in the experience of pain, as well as evidence linking exclusion to conformity. We suggest that genetic variants that increase sensitivity to social cues may predispose individuals to be more sensitive to either social rewards or punishments (or potentially both), which in turn increases conformity and susceptibility to normative social influences more broadly. To this end, we review evidence for genetic moderators of neurochemical responses in the brain, and suggest ways in which genes and pharmacology may modulate sensitivity to social influences. We conclude by proposing an integrative imaging genetics approach to the study of brain mediators and genetic modulators of a variety of social influences on human attitudes, beliefs, and actions. PMID:22701416

Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats.

PubMed

Thomas, Jennifer D; Abou, Elizabeth J; Dominguez, Hector D

2009-01-01

Prenatal alcohol exposure can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Variability in outcome observed among children with FASD is likely related to various pre- and postnatal factors, including nutritional variables. Choline is an essential nutrient that influences brain and behavioral development. Recent animal research indicates that prenatal choline supplementation leads to long-lasting cognitive enhancement, as well as changes in brain morphology, electrophysiology and neurochemistry. The present study examined whether choline supplementation during ethanol exposure effectively reduces fetal alcohol effects. Pregnant dams were exposed to 6.0g/kg/day ethanol via intubation from gestational days (GD) 5-20; pair-fed and lab chow controls were included. During treatment, subjects from each group received choline chloride (250mg/kg/day) or vehicle. Physical development and behavioral development (righting reflex, geotactic reflex, cliff avoidance, reflex suspension and hindlimb coordination) were examined. Subjects prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol's effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Importantly, choline supplementation did not influence peak blood alcohol level or metabolism, indicating that choline's effects were not due to differential alcohol exposure. These data indicate early dietary supplements may reduce the severity of some fetal alcohol effects, findings with important implications for children of women who drink alcohol during pregnancy.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.

PubMed

Franke, Katja; Clarke, Geoffrey D; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4-7 years; human equivalent 14-24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years ( p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition

PubMed Central

Franke, Katja; Clarke, Geoffrey D.; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H.; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W.

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4–7 years; human equivalent 14–24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans. PMID:28443017

Genes and Social Behavior

PubMed Central

Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

2011-01-01

What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

Peptides at the blood brain barrier: Knowing me knowing you.

PubMed

Davis, Thomas P; Abbruscato, Thomas J; Egleton, Richard D

2015-10-01

When the Davis Lab was first asked to contribute to this special edition of Peptides to celebrate the career and influence of Abba Kastin on peptide research, it felt like a daunting task. It is difficult to really understand and appreciate the influence that Abba has had, not only on a generation of peptide researchers, but also on the field of blood brain barrier (BBB) research, unless you lived it as we did. When we look back at our careers and those of our former students, one can truly see that several of Abba's papers played an influential role in the development of our personal research programs. Copyright © 2015 Elsevier Inc. All rights reserved.

Cortical Volume and Developmental Instability Are Independent Predictors of General Intellectual Ability

ERIC Educational Resources Information Center

Thoma, Robert J.; Yeo, Ronald A.; Gangestad, Steven W.; Halgren, Eric; Sanchez, Natalie M.; Lewine, Jeffrey D.

2005-01-01

Measures of developmental instability (DI) reflect developmental disruptions due to genetic and environmental perturbations during normal development. DI might be expected to influence the developmental course of brain development and hence intelligence, and several studies indicate this to be the case. The factors that mediate this relationship…

Biology Today: New Developments in Reproductive Biology.

ERIC Educational Resources Information Center

Flannery, Maura C.

1982-01-01

Briefly reviews research studies focusing on sex differences in the human brain. One study suggests that the presence of androgens either during fetal development or at puberty (rather than their continued presence) determines spatial ability. Cautions against accepting this hypothesis of hormonal influence of spatial ability are discussed.…

Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study.

PubMed

Cardis, E; Varsier, N; Bowman, J D; Deltour, I; Figuerola, J; Mann, S; Moissonnier, M; Taki, M; Vecchia, P; Villegas, R; Vrijheid, M; Wake, K; Wiart, J

2011-09-01

The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk of brain tumours from RF exposure from mobile phones.

Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study

PubMed Central

Varsier, N; Bowman, J D; Deltour, I; Figuerola, J; Mann, S; Moissonnier, M; Taki, M; Vecchia, P; Villegas, R; Vrijheid, M; Wake, K; Wiart, J

2011-01-01

Objectives The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. Methods We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. Results The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. Conclusions While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk of brain tumours from RF exposure from mobile phones. PMID:21659468

Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

PubMed

Hamann, Stephan; Stevens, Jennifer; Vick, Janice Hassett; Bryk, Kristina; Quigley, Charmian A; Berenbaum, Sheri A; Wallen, Kim

2014-11-01

Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls. Copyright © 2014 Elsevier Inc. All rights reserved.

Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

PubMed

Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

2015-12-01

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy.

PubMed

Barton, David A; Esler, Murray D; Dawood, Tye; Lambert, Elisabeth A; Haikerwal, Deepak; Brenchley, Celia; Socratous, Florentia; Hastings, Jacqueline; Guo, Ling; Wiesner, Glen; Kaye, David M; Bayles, Richard; Schlaich, Markus P; Lambert, Gavin W

2008-01-01

The biological basis for the development of major depressive disorder (MDD) remains incompletely understood. To quantify brain serotonin (5-hydroxytryptamine [5-HT]) turnover in patients with MDD. Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Studies were performed in 21 patients fulfilling the DSM-IV and International Statistical Classification of Diseases, 10th Revision diagnostic criteria for MDD and in 40 healthy volunteers. Treatment for patients consisted of SSRI administration for approximately 12 weeks. Brain serotonin turnover before and after SSRI therapy. Brain serotonin turnover was significantly elevated in unmedicated patients with MDD compared with healthy subjects (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 4.4 [4.3] vs 1.6 [2.4] nmol/L, respectively; P = .003). Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the l allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 [4.7] vs 2.7 [2.9] nmol/L, respectively; P = .04). Following SSRI therapy, brain serotonin turnover was substantially reduced (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.0 [4.0] nmol/L prior to treatment vs 2.0 [3.3] nmol/L following therapy; P = .008). Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD.

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

Stem cells for brain repair in neonatal hypoxia-ischemia.

PubMed

Chicha, L; Smith, T; Guzman, R

2014-01-01

Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

Effects of the diet on brain function

NASA Technical Reports Server (NTRS)

Fernstrom, J. D.

1981-01-01

The rates of synthesis by brain neurons of the neurotransmitters serotonin, acetylcholine, and the catecholamines depend on the brain levels of the respective precursor molecules. Brain levels of each precursor are influenced by their blood concentration, and for the amino acid precursors, by the blood levels of other amino acids as well. Since diet readily alters blood concentrations of each of these precursors, it thereby also influences the brain formation of their neutrotransmitter products.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

PubMed

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

Influences on the Test-Retest Reliability of Functional Connectivity MRI and its Relationship with Behavioral Utility.

PubMed

Noble, Stephanie; Spann, Marisa N; Tokoglu, Fuyuze; Shen, Xilin; Constable, R Todd; Scheinost, Dustin

2017-11-01

Best practices are currently being developed for the acquisition and processing of resting-state magnetic resonance imaging data used to estimate brain functional organization-or "functional connectivity." Standards have been proposed based on test-retest reliability, but open questions remain. These include how amount of data per subject influences whole-brain reliability, the influence of increasing runs versus sessions, the spatial distribution of reliability, the reliability of multivariate methods, and, crucially, how reliability maps onto prediction of behavior. We collected a dataset of 12 extensively sampled individuals (144 min data each across 2 identically configured scanners) to assess test-retest reliability of whole-brain connectivity within the generalizability theory framework. We used Human Connectome Project data to replicate these analyses and relate reliability to behavioral prediction. Overall, the historical 5-min scan produced poor reliability averaged across connections. Increasing the number of sessions was more beneficial than increasing runs. Reliability was lowest for subcortical connections and highest for within-network cortical connections. Multivariate reliability was greater than univariate. Finally, reliability could not be used to improve prediction; these findings are among the first to underscore this distinction for functional connectivity. A comprehensive understanding of test-retest reliability, including its limitations, supports the development of best practices in the field. © The Author 2017. Published by Oxford University Press.

Physiology of reproductive worker honey bees (Apis mellifera): insights for the development of the worker caste.

PubMed

Peso, Marianne; Even, Naïla; Søvik, Eirik; Naeger, Nicholas L; Robinson, Gene E; Barron, Andrew B

2016-02-01

Reproductive and behavioural specialisations characterise advanced social insect societies. Typically, the honey bee (Apis mellifera) shows a pronounced reproductive division of labour between worker and queen castes, and a clear division of colony roles among workers. In a queenless condition, however, both of these aspects of social organisation break down. Queenless workers reproduce, forage and maintain their colony operating in a manner similar to communal bees, rather than as an advanced eusocial group. This plasticity in social organisation provides a natural experiment for exploring physiological mechanisms of division of labour. We measured brain biogenic amine (BA) levels and abdominal fat body vitellogenin gene expression levels of workers in queenright and queenless colonies. Age, ovary activation and social environment influenced brain BA levels in honey bees. BA levels were most influenced by ovary activation state in queenless bees. Vitellogenin expression levels were higher in queenless workers than queenright workers, but in both colony environments vitellogenin expression was lower in foragers than non-foragers. We propose this plasticity in the interacting signalling systems that influence both reproductive and behavioural development allows queenless workers to deviate significantly from the typical worker bee reaction norm and develop as reproductively active behavioural generalists.

Integrated and Early Childhood Education: Preparation for Social Development. Theme A: Relevant Provision for Early Childhood.

ERIC Educational Resources Information Center

Axton, J. H. M.

Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…

Gestational age modulates neural correlates of intentional, but not automatic number magnitude processing in children born preterm.

PubMed

Klein, Elise; Moeller, Korbinian; Huber, Stefan; Willmes, Klaus; Kiechl-Kohlendorfer, Ursula; Kaufmann, Liane

2018-04-01

Premature birth is a significant risk factor for learning disabilities in general and mathematics learning difficulties in particular. However, the exact reasons for this relation are still unknown. While typical numerical development is associated with a frontal-to-parietal shift of brain activation with increasing age, influences of gestational age have hardly been considered so far. Therefore, we investigated the influence of gestational age on the neural correlates of number processing in 6- and 7-year-old children born prematurely (n=16). Only the numerical distance effect - as a measure of intentional number magnitude processing - elicited the fronto-parietal activation pattern typically observed for numerical cognition. On the other hand, the size congruity effect - as a measure of automatic number magnitude processing - was associated with activation of brain areas typically attributed to cognitive control. Most importantly, however, we observed that gestational age reliably predicted the frontal-to-parietal shift of activation observed for the numerical distance effect. Our findings seem to indicate that human numerical development may start even before birth and prematurity might hamper neural facilitation of the brain circuitry subserving numerical cognition. In turn, this might contribute to the high risk of premature children to develop mathematical learning difficulties. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

On ways to overcome the magical capacity limit of working memory.

PubMed

Turi, Zsolt; Alekseichuk, Ivan; Paulus, Walter

2018-04-01

The ability to simultaneously process and maintain multiple pieces of information is limited. Over the past 50 years, observational methods have provided a large amount of insight regarding the neural mechanisms that underpin the mental capacity that we refer to as "working memory." More than 20 years ago, a neural coding scheme was proposed for working memory. As a result of technological developments, we can now not only observe but can also influence brain rhythms in humans. Building on these novel developments, we have begun to externally control brain oscillations in order to extend the limits of working memory.

Impact of socio-emotional context, brain development, and pubertal maturation on adolescent risk-taking.

PubMed

Smith, Ashley R; Chein, Jason; Steinberg, Laurence

2013-07-01

While there is little doubt that risk-taking is generally more prevalent during adolescence than before or after, the underlying causes of this pattern of age differences have long been investigated and debated. One longstanding popular notion is the belief that risky and reckless behavior in adolescence is tied to the hormonal changes of puberty. However, the interactions between pubertal maturation and adolescent decision making remain largely understudied. In the current review, we discuss changes in decision making during adolescence, focusing on the asynchronous development of the affective, reward-focused processing system and the deliberative, reasoned processing system. As discussed, differential maturation in the structure and function of brain systems associated with these systems leaves adolescents particularly vulnerable to socio-emotional influences and risk-taking behaviors. We argue that this asynchrony may be partially linked to pubertal influences on development and specifically on the maturation of the affective, reward-focused processing system. Copyright © 2013 Elsevier Inc. All rights reserved.

Rethinking the cognitive revolution from a neural perspective: how overuse/misuse of the term 'cognition' and the neglect of affective controls in behavioral neuroscience could be delaying progress in understanding the BrainMind.

PubMed

Cromwell, Howard Casey; Panksepp, Jaak

2011-10-01

Words such as cognition, motivation and emotion powerfully guide theory development and the overall aims and goals of behavioral neuroscience research. Once such concepts are accepted generally as natural aspects of the brain, their influence can be pervasive and long lasting. Importantly, the choice of conceptual terms used to describe and study mental/neural functions can also constrain research by forcing the results into seemingly useful 'conceptual' categories that have no discrete reality in the brain. Since the popularly named 'cognitive revolution' in psychological science came to fruition in the early 1970s, the term cognitive or cognition has been perhaps the most widely used conceptual term in behavioral neuroscience. These terms, similar to other conceptual terms, have potential value if utilized appropriately. We argue that recently the term cognition has been both overused and misused. This has led to problems in developing a usable shared definition for the term and to promotion of possible misdirections in research within behavioral neuroscience. In addition, we argue that cognitive-guided research influenced primarily by top-down (cortical toward subcortical) perspectives without concurrent non-cognitive modes of bottom-up developmental thinking, could hinder progress in the search for new treatments and medications for psychiatric illnesses and neurobehavioral disorders. Overall, linkages of animal research insights to human psychology may be better served by bottom-up (subcortical to cortical) affective and motivational 'state-control' perspectives, simply because the lower networks of the brain are foundational for the construction of higher 'information-processing' aspects of mind. Moving forward, rapidly expanding new techniques and creative methods in neuroscience along with more accurate brain concepts, may help guide the development of new therapeutics and hopefully more accurate ways to describe and explain brain-behavior relationships. Copyright © 2011 Elsevier Ltd. All rights reserved.

The "chicken-and-egg" development of political opinions.

PubMed

Beattie, Peter

2017-01-01

Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a "chicken-and-egg" question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.

Kynurenine pathway metabolism and the microbiota-gut-brain axis.

PubMed

Kennedy, P J; Cryan, J F; Dinan, T G; Clarke, G

2017-01-01

It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data

PubMed Central

Davis, Faith G.; Dolecek, Therese A.; McCarthy, Bridget J.; Villano, John L.

2012-01-01

Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States. PMID:22898372

Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data.

PubMed

Davis, Faith G; Dolecek, Therese A; McCarthy, Bridget J; Villano, John L

2012-09-01

Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States.

How hormones influence composition and physiological function of the brain-blood barrier.

PubMed

Hampl, R; Bičíková, M; Sosvorová, L

2015-01-01

Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain

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

Tyler, Christina R.; Hafez, Alexander K.; Solomon, Elizabeth R.

Epidemiological studies report that arsenic exposure via drinking water adversely impacts cognitive development in children and, in adults, can lead to greater psychiatric disease susceptibility, among other conditions. While it is known that arsenic toxicity has a profound effect on the epigenetic landscape, very few studies have investigated its effects on chromatin architecture in the brain. We have previously demonstrated that exposure to a low level of arsenic (50 ppb) during all three trimesters of fetal/neonatal development induces deficits in adult hippocampal neurogenesis in the dentate gyrus (DG), depressive-like symptoms, and alterations in gene expression in the adult mouse brain.more » As epigenetic processes control these outcomes, here we assess the impact of our developmental arsenic exposure (DAE) paradigm on global histone posttranslational modifications and associated chromatin-modifying proteins in the dentate gyrus and frontal cortex (FC) of adult male and female mice. DAE influenced histone 3 K4 trimethylation with increased levels in the male DG and FC and decreased levels in the female DG (no change in female FC). The histone methyltransferase MLL exhibited a similar sex- and region-specific expression profile as H3K4me3 levels, while histone demethylase KDM5B expression trended in the opposite direction. DAE increased histone 3 K9 acetylation levels in the male DG along with histone acetyltransferase (HAT) expression of GCN5 and decreased H3K9ac levels in the male FC along with decreased HAT expression of GCN5 and PCAF. DAE decreased expression of histone deacetylase enzymes HDAC1 and HDAC2, which were concurrent with increased H3K9ac levels but only in the female DG. Levels of H3 and H3K9me3 were not influenced by DAE in either brain region of either sex. These findings suggest that exposure to a low, environmentally relevant level of arsenic during development leads to long-lasting changes in histone methylation and acetylation in the adult brain due to aberrant expression of epigenetic machinery based on region and sex. - Highlights: • Brain tissue from adult mice with developmental arsenic exposure (DAE) was used. • DAE impacted histone methylation and associated methyltransferases based on sex. • DAE differentially altered histone acetylation based on brain region. • DAE altered HATs in males and HDACs in females. • Epigenetic modifier expression correlated with the associated histone modification.« less

Association of Child Poverty, Brain Development, and Academic Achievement

PubMed Central

Hair, Nicole L.; Hanson, Jamie L.; Wolfe, Barbara L.; Pollak, Seth D.

2015-01-01

IMPORTANCE Children living in poverty generally perform poorly in school, with markedly lower standardized test scores and lower educational attainment. The longer children live in poverty, the greater their academic deficits. These patterns persist to adulthood, contributing to lifetime-reduced occupational attainment. OBJECTIVE To determine whether atypical patterns of structural brain development mediate the relationship between household poverty and impaired academic performance. DESIGN, SETTING, AND PARTICIPANTS Longitudinal cohort study analyzing 823 magnetic resonance imaging scans of 389 typically developing children and adolescents aged 4 to 22 years from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development with complete sociodemographic and neuroimaging data. Data collection began in November 2001 and ended in August 2007. Participants were screened for a variety of factors suspected to adversely affect brain development, recruited at 6 data collection sites across the United States, assessed at baseline, and followed up at 24-month intervals for a total of 3 periods. Each study center used community-based sampling to reflect regional and overall US demographics of income, race, and ethnicity based on the US Department of Housing and Urban Development definitions of area income. One-quarter of sample households reported the total family income below 200% of the federal poverty level. Repeated observations were available for 301 participants. EXPOSURE Household poverty measured by family income and adjusted for family size as a percentage of the federal poverty level. MAIN OUTCOMES AND MEASURES Children’s scores on cognitive and academic achievement assessments and brain tissue, including gray matter of the total brain, frontal lobe, temporal lobe, and hippocampus. RESULTS Poverty is tied to structural differences in several areas of the brain associated with school readiness skills, with the largest influence observed among children from the poorest households. Regional gray matter volumes of children below 1.5 times the federal poverty level were 3 to 4 percentage points below the developmental norm (P < .05). A larger gap of 8 to 10 percentage points was observed for children below the federal poverty level (P < .05). These developmental differences had consequences for children’s academic achievement. On average, children from low-income households scored 4 to 7 points lower on standardized tests (P < .05). As much as 20% of the gap in test scores could be explained by maturational lags in the frontal and temporal lobes. CONCLUSIONS AND RELEVANCE The influence of poverty on children’s learning and achievement is mediated by structural brain development. To avoid long-term costs of impaired academic functioning, households below 150% of the federal poverty level should be targeted for additional resources aimed at remediating early childhood environments. PMID:26192216

The microbiome: stress, health and disease.

PubMed

Moloney, Rachel D; Desbonnet, Lieve; Clarke, Gerard; Dinan, Timothy G; Cryan, John F

2014-02-01

Bacterial colonisation of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathology of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome-brain-gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.

Testosterone affects language areas of the adult human brain.

PubMed

Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

2016-05-01

Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Endocrine modulation of the adolescent brain: a review.

PubMed

Vigil, Pilar; Orellana, Renán F; Cortés, Manuel E; Molina, Carmen T; Switzer, Barbara E; Klaus, Hanna

2011-12-01

Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

A systematic literature review of sex differences in childhood language and brain development.

PubMed

Etchell, Andrew; Adhikari, Aditi; Weinberg, Lauren S; Choo, Ai Leen; Garnett, Emily O; Chow, Ho Ming; Chang, Soo-Eun

2018-06-01

The extent of sex differences in childhood language development is unclear. We conducted a systematic literature review synthesizing results from studies examining sex differences in brain structure and function relevant to language development during childhood. We searched PubMed and Scopus databases, and this returned a total of 46 published studies meeting criteria for inclusion that directly examined sex differences in brain development relevant to language function in children. The results indicate that: (a) sex differences in brain structure or function do not necessarily lead to differences in language task performance; (b) evidence for sex differences in brain and language development are limited; (c) when present, sex differences often interact with a variety of factors such as age and task. Overall, the magnitude of sexual dimorphism of brain developmental trajectories associated with language is not as significant as previously thought. Sex differences were found, however, in studies employing tighter age ranges. This suggests that sex differences may be more prominent during certain developmental stages but are negligible in other stages, likely due to different rates of maturation between the sexes. More research is needed to improve our understanding of how sex differences may arise due to the influence of sex hormones and developmental stages, and how these differences may lead to differences in various language task performance. These studies are expected to provide normative information that may be used in studies examining neurodevelopmental disorders that frequently affect more males than females, and also often affect language development. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology

PubMed Central

Booij, Linda; Tremblay, Richard E.; Szyf, Moshe; Benkelfat, Chawki

2015-01-01

Background Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development. Methods Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists. Results Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region–specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms. Limitations There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain. Conclusion A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology. PMID:25285876

State-of-the-art considerations in small cell lung cancer brain metastases

PubMed Central

Lukas, Rimas V.; Gondi, Vinai; Kamson, David O.; Kumthekar, Priya; Salgia, Ravi

2017-01-01

Background Small cell lung cancer (SCLC) frequently leads to development of brain metastases. These unfortunately continue to be associated with short survival. Substantial advances have been made in our understanding of the underlying biology of disease. This understanding on the background of previously evaluated and currently utilized therapeutic treatments can help guide the next steps in investigations into this disease with the potential to influence future treatments. Design A comprehensive review of the literature covering epidemiology, pathophysiology, imaging characteristics, prognosis, and therapeutic management of SCLC brain metastases was performed. Results SCLC brain metastases continue to have a poor prognosis. Both unique aspects of SCLC brain metastases as well as features seen more universally across other solid tumor brain metastases are discussed. Systemic therapeutic studies and radiotherapeutic approaches are reviewed. Conclusions A clearer understanding of SCLC brain metastases will help lay the framework for studies which will hopefully translate into meaningful therapeutic options for these patients. PMID:29050358

Sexing the brain: the science and pseudoscience of sex differences.

PubMed

Rogers, Lesley J

2010-06-01

A recent upsurge in unitary biological explanations for gender differences in behavior (i.e. that they are "hard-wired" in the genetic code), put forward not only in books written for a general audience but also in scientific papers, makes it important to examine the fallacies of these ideas. Such genetic and hormonal explanations of human behavior, formulated with little consideration of the influences of experience, and often without taking experience into account at all, are part of a new wave of genetic explanations for a broad range of human behavior, as explained in the paper. These ideas are far from new; moreover, they are pseudoscientific and are used for political influence under the guise of science. They are a conservative social force that maintains social and educational inequalities between women and men. This paper explains that causal explanations of differences between the sexes are of two completely different types: unitary (genetic determinist) versus interactive explanations. The false reasoning used to support genetic determinist explanations of sex differences in behavior is discussed. To illustrate what biology really tells us about gender differentiation, the paper discusses the interactive roles of genetic, hormonal and environmental influences on the development of gender differences. These interactions are illustrated using two model biological systems (e.g. the intertwined influences of genes, sex hormones and experience on the development of sex differences in behavior in rats, and sex differences in neuronal connections in chickens). There is plenty of scientific evidence to show the complex interactive, and ever changing, influences of experience and genes that take place as an organism develops and throughout its life. Malleability of brain and behavior can be shown clearly using animal models, and the processes involved apply also to the development of brain and behavior in humans. We diminish our understanding of the functions of a host of contributing factors to gender differentiation by parceling out the largest portion of control to the genes. The biology and behavior of humans is dynamic and flexible and need not restrict women to inferior positions in society. 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination.

PubMed

Gibson, Daniel A; Ma, Le

2011-08-01

Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab (unpublished results) and others, and can be extended to other viruses, such as lentivirus, as well as to the expression of shRNA or dominant active proteins. Furthermore, by combining this technique with electrophysiology as well as recently-developed optical imaging tools, this method provides a new strategy to study how genetic pathways influence neural circuit development and function in mice and rats.

The influence of pretreatment characteristics and radiotherapy parameters on time interval to development of radiation-associated meningioma.

PubMed

Paulino, Arnold C; Ahmed, Irfan M; Mai, Wei Y; Teh, Bin S

2009-12-01

To identify pretreatment characteristics and radiotherapy parameters which may influence time interval to development of radiation-associated meningioma (RAM). A Medline/PUBMED search of articles dealing with RAM yielded 66 studies between 1981 and 2006. Factors analyzed included patient age and gender, type of initial tumor treated, radiotherapy (RT) dose and volume, and time interval from RT to development of RAM. A total of 143 patients with a median age at RT of 12 years form the basis of this report. The most common initial tumors or conditions treated with RT were medulloblastoma (n = 27), pituitary adenoma (n = 20), acute lymphoblastic leukemia (n = 20), low-grade astrocytoma (n = 19), and tinea capitis (n = 14). In the 116 patients whose RT fields were known, 55 (47.4%) had a portion of the brain treated, whereas 32 (27.6%) and 29 (25.0%) had craniospinal and whole-brain fields. The median time from RT to develop a RAM or latent time (LT) was 19 years (range, 1-63 years). Male gender (p = 0.001), initial diagnosis of leukemia (p = 0.001), and use of whole brain or craniospinal field (p

The Influence of Pretreatment Characteristics and Radiotherapy Parameters on Time Interval to Development of Radiation-Associated Meningioma

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

Paulino, Arnold C., E-mail: apaulino@tmhs.or; Ahmed, Irfan M.; Mai, Wei Y.

2009-12-01

Purpose: To identify pretreatment characteristics and radiotherapy parameters which may influence time interval to development of radiation-associated meningioma (RAM). Methods and Materials: A Medline/PUBMED search of articles dealing with RAM yielded 66 studies between 1981 and 2006. Factors analyzed included patient age and gender, type of initial tumor treated, radiotherapy (RT) dose and volume, and time interval from RT to development of RAM. Results: A total of 143 patients with a median age at RT of 12 years form the basis of this report. The most common initial tumors or conditions treated with RT were medulloblastoma (n = 27), pituitarymore » adenoma (n = 20), acute lymphoblastic leukemia (n = 20), low-grade astrocytoma (n = 19), and tinea capitis (n = 14). In the 116 patients whose RT fields were known, 55 (47.4%) had a portion of the brain treated, whereas 32 (27.6%) and 29 (25.0%) had craniospinal and whole-brain fields. The median time from RT to develop a RAM or latent time (LT) was 19 years (range, 1-63 years). Male gender (p = 0.001), initial diagnosis of leukemia (p = 0.001), and use of whole brain or craniospinal field (p <= 0.0001) were associated with a shorter LT, whereas patients who received lower doses of RT had a longer LT (p < 0.0001). Conclusions: The latent time to develop a RAM was related to gender, initial tumor type, radiotherapy volume, and radiotherapy dose.« less

Functional Plasticity in Childhood Brain Disorders: When, What, How, and Whom to Assess

PubMed Central

Dennis, Maureen; Spiegler, Brenda J.; Simic, Nevena; Sinopoli, Katia J.; Wilkinson, Amy; Yeates, Keith Owen; Taylor, H. Gerry; Bigler, Erin D.; Fletcher, Jack M.

2014-01-01

At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome. PMID:24821533

Cloning, localization and differential expression of Neuropeptide-Y during early brain development and gonadal recrudescence in the catfish, Clarias gariepinus.

PubMed

Sudhakumari, Cheni-Chery; Anitha, Arumugam; Murugananthkumar, Raju; Tiwari, Dinesh Kumar; Bhasker, Dharavath; Senthilkumaran, Balasubramanian; Dutta-Gupta, Aparna

2017-09-15

Neuropeptide-Y (NPY) has diverse physiological functions which are extensively studied in vertebrates. However, regulatory role of NPY in relation to brain ontogeny and recrudescence with reference to reproduction is less understood in fish. Present report for the first time evaluated the significance of NPY by transient esiRNA silencing and also analyzed its expression during brain development and gonadal recrudescence in the catfish, Clarias gariepinus. As a first step, full-length cDNA of NPY was cloned from adult catfish brain, which shared high homology with its counterparts from other teleosts upon phylogenetic analysis. Tissue distribution revealed dominant expression of NPY in brain and testis. NPY expression increased during brain development wherein the levels were higher in 100 and 150days post hatch females than the respective age-matched males. Seasonal cycle analysis showed high expression of NPY in brain during pre-spawning phase in comparison with other reproductive phases. Localization studies exhibited the presence of NPY, abundantly, in the regions of preoptic area, hypothalamus and pituitary. Transient silencing of NPY-esiRNA directly into the brain significantly decreased NPY expression in both the male and female brain of catfish which further resulted in significant decrease of transcripts of tryptophan hydroxylase 2, catfish gonadotropin-releasing hormone (cfGnRH), tyrosine hydroxylase and 3β-hydroxysteroid dehydrogenase in brain and luteinizing hormone-β/gonadotropin-II (lh-β/GTH-II) in pituitary exhibiting its influence on gonadal axis. In addition, significant decrease of several ovary-related transcripts was observed in NPY-esiRNA silenced female catfish, indicating the plausible role of NPY in ovary through cfGnRH-GTH axis. Copyright © 2017 Elsevier Inc. All rights reserved.

What is special about the adolescent (JME) brain?

PubMed

Craiu, Dana

2013-07-01

Juvenile myoclonic epilepsy (JME) involves cortico-thalamo-cortical networks. Thalamic, frontal gray matter, connectivity, and neurotransmitter disturbances have been demonstrated by structural/functional imaging studies. Few patients with JME show mutations in genes coding ion channels or GABAA (gamma-aminobutyric acid) receptor subunits. Recent research points to EFHC1 gene mutations leading to microdysgenesis and possible aberrant circuitry. Imaging studies have shown massive structural/functional changes of normally developing adolescent brain structures maturing at strikingly different rates and times. Gray matter (GM) volume diminishes in cortical areas (frontal and parietal) and deep structures (anterior thalamus, putamen, and caudate). Diffusion tensor imaging (DTI) findings support continued microstructural change in WM (white matter) during late adolescence with robust developmental changes in thalamocortical connectivity. The GABAA receptor distribution and specific receptor subunits' expression patterns change with age from neonate to adolescent/adult, contributing to age-related changes in brain excitability. Hormonal influence on brain structure development during adolescence is presented. Possible implications of brain changes during adolescence on the course of JME are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Issues of cultural diversity in acquired brain injury (ABI) rehabilitation.

PubMed

Lequerica, Anthony; Krch, Denise

2014-01-01

With the general population in the United States becoming increasingly diverse, it is important for rehabilitation professionals to develop the capacity to provide culturally sensitive treatment. This is especially relevant when working with minority populations who have a higher risk for brain injury and poorer rehabilitation outcomes. This article presents a number of clinical vignettes to illustrate how cultural factors can influence behavior in patients recovering from brain injury, as well as rehabilitation staff. The main objectives are to raise awareness among clinicians and stimulate research ideas by highlighting some real world examples of situations where a specialized, patient-centered approach needs to consider factors of cultural diversity. Because one's own world view impacts the way we see the world and interpret behavior, it is important to understand one's own ethnocentrism when dealing with a diverse population of patients with brain injury where behavioral sequelae are often expected. Being able to see behavior after brain injury with an open mind and taking into account cultural and contextual factors is an important step in developing culturally competent rehabilitation practices.

A neuroscience agenda for counseling psychology research.

PubMed

Gonçalves, Oscar F; Perrone-McGovern, Kristin M

2014-10-01

Recent advances in the field of neuroscience have dramatically changed our understanding of brain-behavior relationships. In this article, we illustrate how neuroscience can provide a conceptual and methodological framework to understand our clients within a transdiagnostic developmental perspective. We provide directions for integrating neuroscience into future process and outcome research. We present examples on how neuroscience can be integrated into researching the effects of contextual counseling interventions. We posit that interpersonal and environmental factors, such as neurotoxic factors (e.g., emotional neglect, stress), positive neurodevelopmental factors (e.g., nurturing and caring, environmental enrichment), and therapeutic interventions influence psychological processes (executive control, behavioral flexibility, reinforcement learning and approach motivation, emotional expression and regulation, self-representation and theory of mind). These psychological processes influence brain networks (attention, motivational, emotional regulation, social cognition), which influence cognitive, social, emotional, identity, and vocational development. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse.

PubMed

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

PubMed Central

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor. PMID:29479302

Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

PubMed Central

Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

2015-01-01

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

Neuronal survival in the brain: neuron type-specific mechanisms.

PubMed

Pfisterer, Ulrich; Khodosevich, Konstantin

2017-03-02

Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

Mother-infant interactions and regional brain volumes in infancy: an MRI study.

PubMed

Sethna, Vaheshta; Pote, Inês; Wang, Siying; Gudbrandsen, Maria; Blasi, Anna; McCusker, Caroline; Daly, Eileen; Perry, Emily; Adams, Kerrie P H; Kuklisova-Murgasova, Maria; Busuulwa, Paula; Lloyd-Fox, Sarah; Murray, Lynne; Johnson, Mark H; Williams, Steven C R; Murphy, Declan G M; Craig, Michael C; McAlonan, Grainne M

2017-07-01

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.

The role of gangliosides in brain development and the potential benefits of perinatal supplementation.

PubMed

Ryan, Jennifer M; Rice, Gregory E; Mitchell, Murray D

2013-11-01

The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research. © 2013.

Is Polysialylated NCAM Not Only a Regulator during Brain Development But also during the Formation of Other Organs?

PubMed Central

Galuska, Christina E.; Lütteke, Thomas; Galuska, Sebastian P.

2017-01-01

In mammals several cell adhesion molecules are involved during the pre- and postnatal development of all organ systems. A very prominent member of this family is the neural cell adhesion molecule (NCAM). Interestingly, NCAM can be a target for a special form of posttranslational modification: polysialylation. Whereas nearly all extracellular proteins bear mono-sialic acid residues, only a very small group can be polysialylated. Polysialic acid is a highly negatively-charged sugar polymer and can comprise more than 90 sialic acid residues in postnatal mouse brains increasing dramatically the hydrodynamic radius of their carriers. Thus, adhesion and communication processes on cell surfaces are strongly influenced allowing, e.g., the migration of neuronal progenitor cells. In the developing brain the essential role of polysialylated NCAM has been demonstrated in many studies. In comparison to the neuronal system, however, during the formation of other organs the impact of the polysialylated form of NCAM is not well characterized and the number of studies is limited so far. This review summarizes these observations and discusses possible roles of polysialylated NCAM during the development of organs other than the brain. PMID:28448440

Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

PubMed Central

Zueva, Marina V.

2015-01-01

The theory that ties normal functioning and pathology of the brain and visual system with the spatial–temporal structure of the visual and other sensory stimuli is described for the first time in the present study. The deficit of fractal complexity of environmental influences can lead to the distortion of fractal complexity in the visual pathways of the brain and abnormalities of development or aging. The use of fractal light stimuli and fractal stimuli of other modalities can help to restore the functions of the brain, particularly in the elderly and in patients with neurodegenerative disorders or amblyopia. Non-linear dynamics of these physiological processes have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. From birth to old age, we live in a non-linear world, in which objects and processes with the properties of fractality and non-linearity surround us. Against this background, the evolution of man took place and all periods of life unfolded. Works of art created by man may also have fractal properties. The positive influence of music on cognitive functions is well-known. Insufficiency of sensory experience is believed to play a crucial role in the pathogenesis of amblyopia and age-dependent diseases. The brain is very plastic in its early development, and the plasticity decreases throughout life. However, several studies showed the possibility to reactivate the adult’s neuroplasticity in a variety of ways. We propose that a non-linear structure of sensory information on many spatial and temporal scales is crucial to the brain health and fractal regulation of physiological rhythms. Theoretical substantiation of the author’s theory is presented. Possible applications and the future research that can experimentally confirm or refute the theoretical concept are considered. PMID:26236232

Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

PubMed

D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

2015-07-29

Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how the immune system signals the brain to alter brain function. These findings broaden our understanding of how probiotics may beneficially affect brain function in the context of inflammation occurring within the body and may open potential new therapeutic alternatives for the treatment of these alterations in behavior that can greatly affect patient quality of life. Copyright © 2015 the authors 0270-6474/15/3510822-10$15.00/0.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

Study protocol: imaging brain development in the Childhood to Adolescence Transition Study (iCATS).

PubMed

Simmons, Julian G; Whittle, Sarah L; Patton, George C; Dudgeon, Paul; Olsson, Craig; Byrne, Michelle L; Mundy, Lisa K; Seal, Marc L; Allen, Nicholas B

2014-04-30

Puberty is a critical developmental phase in physical, reproductive and socio-emotional maturation that is associated with the period of peak onset for psychopathology. Puberty also drives significant changes in brain development and function. Research to date has focused on gonadarche, driven by the hypothalamic-pituitary-gonadal axis, and yet increasing evidence suggests that the earlier pubertal stage of adrenarche, driven by the hypothalamic-pituitary-adrenal axis, may play a critical role in both brain development and increased risk for disorder. We have established a unique cohort of children who differ in their exposure to adrenarcheal hormones. This presents a unique opportunity to examine the influence of adrenarcheal timing on brain structural and functional development, and subsequent health outcomes. The primary objective of the study is to explore the hypothesis that patterns of structural and functional brain development will mediate the relationship between adrenarcheal timing and indices of affect, self-regulation, and mental health symptoms collected across time (and therefore years of development). Children were recruited based upon earlier or later timing of adrenarche, from a larger cohort, with 128 children (68 female; M age 9.51 years) and one of their parents taking part. Children completed brain MRI structural and functional sequences, provided saliva samples for adrenarcheal hormones and immune biomarkers, hair for long-term cortisol levels, and completed questionnaires, anthropometric measures and an IQ test. Parents completed questionnaires reporting on child behaviour, development, health, traumatic events, and parental report of family environment and parenting style. This study, by examining the neurobiological and behavioural consequences of relatively early and late exposure to adrenarche, has the potential to significantly impact our understanding of pubertal risk processes.

D-serine signalling as a prominent determinant of neuronal-glial dialogue in the healthy and diseased brain.

PubMed

Billard, J-M

2008-10-01

Rather different from their initial image as passive supportive cells of the CNS, the astrocytes are now considered as active partners at synapses, able to release a set of gliotransmitter-like substances to modulate synaptic communication within neuronal networks. Whereas glutamate and ATP were first regarded as main determinants of gliotransmission, growing evidence indicates now that the amino acid D-serine is another important player in the neuronal-glial dialogue. Through the regulation of glutamatergic neurotransmission through both N-methyl-D-aspartate (NMDA-R) and non-NMDA-R, D-serine is helping in modelling the appropriate connections in the developing brain and influencing the functional plasticity within neuronal networks throughout lifespan. The understanding of D-serine signalling, which has increased linearly in the last few years, gives new insights into the critical role of impaired neuronal-glial communication in the diseased brain, and offers new opportunities for developing relevant strategies to treat cognitive deficits associated to brain disorders.

Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer’s disease

PubMed Central

De Felice, Fernanda G.; Lourenco, Mychael V.

2015-01-01

Brain metabolic dysfunction is known to influence brain activity in several neurological disorders, including Alzheimer’s disease (AD). In fact, deregulation of neuronal metabolism has been postulated to play a key role leading to the clinical outcomes observed in AD. Besides deficits in glucose utilization in AD patients, recent evidence has implicated neuroinflammation and endoplasmic reticulum (ER) stress as components of a novel form of brain metabolic stress that develop in AD and other neurological disorders. Here we review findings supporting this novel paradigm and further discuss how these mechanisms seem to participate in synapse and cognitive impairments that are germane to AD. These deleterious processes resemble pathways that act in peripheral tissues leading to insulin resistance and glucose intolerance, in an intriguing molecular connection linking AD to diabetes. The discovery of detailed mechanisms leading to neuronal metabolic stress may be a key step that will allow the understanding how cognitive impairment develops in AD, thereby offering new avenues for effective disease prevention and therapeutic targeting. PMID:26042036

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

D-serine signalling as a prominent determinant of neuronal-glial dialogue in the healthy and diseased brain

PubMed Central

Billard, J-M

2008-01-01

Rather different from their initial image as passive supportive cells of the CNS, the astrocytes are now considered as active partners at synapses, able to release a set of gliotransmitter-like substances to modulate synaptic communication within neuronal networks. Whereas glutamate and ATP were first regarded as main determinants of gliotransmission, growing evidence indicates now that the amino acid D-serine is another important player in the neuronal-glial dialogue. Through the regulation of glutamatergic neurotransmission through both N-methyl-D-aspartate (NMDA-R) and non-NMDA-R, D-serine is helping in modelling the appropriate connections in the developing brain and influencing the functional plasticity within neuronal networks throughout lifespan. The understanding of D-serine signalling, which has increased linearly in the last few years, gives new insights into the critical role of impaired neuronal-glial communication in the diseased brain, and offers new opportunities for developing relevant strategies to treat cognitive deficits associated to brain disorders. PMID:18363840

[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill].

PubMed

López Moratalla, Natalia; Errasti Alcalá, Tania; Santiago, Esteban

2011-01-01

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

PubMed

Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R

2016-03-01

Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

The Effect of Molecular Diagnostics on the Treatment of Glioma.

PubMed

Bush, Nancy Ann Oberheim; Butowski, Nicholas

2017-04-01

This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions. Several of these markers are also being used as therapeutic targets. We review the use of several molecular diagnostics in gliomas and discuss their impact on drug development and clinical trial design. In the future, molecular characterization based on a specific genomic, proteomic as well as transcriptomes for bioformatics analysis will provide clinicians the ability to rationally select drugs with actionable targets for each patient.

The Development of Eating Behavior - Biology and Context

PubMed Central

Gahagan, Sheila

2012-01-01

Eating is necessary for survival, gives great pleasure and can be perturbed leading to undernutrition, overnutrition and eating disorders. The development of feeding in humans relies on complex interplay between homeostatic mechanisms; neural reward systems; and child motor, sensory and socio-emotional capability. Furthermore, parenting, social influences and the food environment influence the development of eating behavior. The rapid expansion of new knowledge in this field, from basic science to clinical and community-based research, is expected to lead to urgently needed research in support of effective, evidence-based prevention and treatment strategies for undernutrition, overnutrition and eating disorders in early childhood. Using a biopsychosocial approach, this review covers current knowledge of the development of eating behavior from the brain to the individual child, taking into account important contextual influences. PMID:22472944

Molecular profiling of the developing avian telencephalon: regional timing and brain subdivision continuities.

PubMed

Chen, Chun-Chun; Winkler, Candace M; Pfenning, Andreas R; Jarvis, Erich D

2013-11-01

In our companion study (Jarvis et al. [2013] J Comp Neurol. doi: 10.1002/cne.23404) we used quantitative brain molecular profiling to discover that distinct subdivisions in the avian pallium above and below the ventricle and the associated mesopallium lamina have similar molecular profiles, leading to a hypothesis that they may form as continuous subdivisions around the lateral ventricle. To explore this hypothesis, here we profiled the expression of 16 genes at eight developmental stages. The genes included those that define brain subdivisions in the adult and some that are also involved in brain development. We found that phyletic hierarchical cluster and linear regression network analyses of gene expression profiles implicated single and mixed ancestry of these brain regions at early embryonic stages. Most gene expression-defined pallial subdivisions began as one ventral or dorsal domain that later formed specific folds around the lateral ventricle. Subsequently a clear ventricle boundary formed, partitioning them into dorsal and ventral pallial subdivisions surrounding the mesopallium lamina. These subdivisions each included two parts of the mesopallium, the nidopallium and hyperpallium, and the arcopallium and hippocampus, respectively. Each subdivision expression profile had a different temporal order of appearance, similar in timing to the order of analogous cell types of the mammalian cortex. Furthermore, like the mammalian pallium, expression in the ventral pallial subdivisions became distinct during prehatch development, whereas the dorsal portions did so during posthatch development. These findings support the continuum hypothesis of avian brain subdivision development around the ventricle and influence hypotheses on homologies of the avian pallium with other vertebrates. Copyright © 2013 Wiley Periodicals, Inc.

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.

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.

A Survey of English Sixth Formers' Knowledge of Early Brain Development.

PubMed

Nolan, Mary

2017-10-01

Objectives To ascertain the knowledge of young people aged 16 to 19 of early brain development and their attitudes towards the care of babies and preschool children. Design Cross-sectional, school- and college-based survey including all sixth form students present on the days of data collection. The survey instrument comprised forced-choice questions in four sections: Demographics, Perceptions and Understanding of Early Childhood Development, Parental Behaviors to Support Early Brain development, and Resource Needs and Usage. Setting Two sixth form schools and one sixth form college in three towns of varying affluence in the West Midlands of the United Kingdom. Method The survey was mounted online and completed by 905 students who returned it directly to the researcher. Results Most students knew that tobacco, alcohol, and drugs are hazardous in pregnancy, and many recognized the impact of maternal stress on fetal brain development. Many believed that babies can be "spoiled" and did not appreciate the importance of reading to babies and of the relationship between play and early brain development. A significant minority thought that physical activity and a healthy diet have little impact on young children's development. Respondents said they would turn firstly to their parents for advice on baby care rather than professionals. Conclusion Young people need educating about parenting activities that support the all-round healthy development of infants. The importance of a healthy diet, physical activity, reading, and play should be included in sixth form curricula and antenatal classes. Consideration should be given to educating grandparents because of their influence on new parents.

May the Force Be With You: The Light and Dark Sides of the Microbiota-Gut-Brain Axis in Neuropsychiatry.

PubMed

Sherwin, Eoin; Sandhu, Kiran V; Dinan, Timothy G; Cryan, John F

2016-11-01

The role of the gut microbiota in health and disease is becoming increasingly recognized. The microbiota-gut-brain axis is a bi-directional pathway between the brain and the gastrointestinal system. The bacterial commensals in our gut can signal to the brain through a variety of mechanisms, which are slowly being resolved. These include the vagus nerve, immune mediators and microbial metabolites, which influence central processes such as neurotransmission and behaviour. Dysregulation in the composition of the gut microbiota has been identified in several neuropsychiatric disorders, such as autism, schizophrenia and depression. Moreover, preclinical studies suggest that they may be the driving force behind the behavioural abnormalities observed in these conditions. Understanding how bacterial commensals are involved in regulating brain function may lead to novel strategies for development of microbiota-based therapies for these neuropsychiatric disorders.

Relationship between diet, the gut microbiota, and brain function.

PubMed

Tengeler, Anouk C; Kozicz, Tamas; Kiliaan, Amanda J

2018-04-28

The human intestinal microbiota, comprising trillions of microorganisms, exerts a substantial effect on the host. The microbiota plays essential roles in the function and development of several physiological processes, including those in the brain. A disruption in the microbial composition of the gut has been associated with many metabolic, inflammatory, neurodevelopmental, and neurodegenerative disorders. Nutrition is one of several key factors that shape the microbial composition during infancy and throughout life, thereby affecting brain structure and function. This review examines the effect of the gut microbiota on brain function. The ability of external factors, such as diet, to influence the microbial composition implies a certain vulnerability of the gut microbiota. However, it also offers a potential therapeutic strategy for ameliorating symptoms of mental and physical disorders. Therefore, this review examines the potential effect of nutritional components on gut microbial composition and brain function.

[The significance of the Montessori method and phenomenon with a particular view to the therapy of the aphasics (author's transl)].

PubMed

Birchmeier-Nussbaumer, A K

1980-05-01

The methods of the Italian physician Maria Montessori influenced the development of modern learning practices. There is general agreement that the Montessori phenomenon is personality forming. Aspects of this method, which are relevant for the rehabilitation of the brain-damaged and, in particular, the aphasics are presented. Possible shifts of emphasis within the relationship therapist - method - patient are analysed. Examples are used to outline in how far an increasingly patient-oriented therapy can influence the development of the aphasic patient.

The pathophysiology of post-stroke aphasia: A network approach.

PubMed

Thiel, Alexander; Zumbansen, Anna

2016-06-13

Post-stroke aphasia syndromes as a clinical entity arise from the disruption of brain networks specialized in language production and comprehension due to permanent focal ischemia. This approach to post-stroke aphasia is based on two pathophysiological concepts: 1) Understanding language processing in terms of distributed networks rather than language centers and 2) understanding the molecular pathophysiology of ischemic brain injury as a dynamic process beyond the direct destruction of network centers and their connections. While considerable progress has been made in the past 10 years to develop such models on a systems as well as a molecular level, the influence of these approaches on understanding and treating clinical aphasia syndromes has been limited. In this article, we review current pathophysiological concepts of ischemic brain injury, their relationship to altered information processing in language networks after ischemic stroke and how these mechanisms may be influenced therapeutically to improve treatment of post-stroke aphasia. Understanding the pathophysiological mechanism of post-stroke aphasia on a neurophysiological systems level as well as on the molecular level becomes more and more important for aphasia treatment, as the field moves from standardized therapies towards more targeted individualized treatment strategies comprising behavioural therapies as well as non-invasive brain stimulation (NIBS).

Regulation of Brain Activity in the Fusiform Face and Parahippocampal Place Areas in 7-11-Year-Old Children

ERIC Educational Resources Information Center

Vuontela, Virve; Jiang, Ping; Tokariev, Maksym; Savolainen, Petri; Ma, YuanYe; Aronen, Eeva T.; Fontell, Tuija; Liiri, Tiina; Ahlstrom, Matti; Salonen, Oili; Carlson, Synnove

2013-01-01

Developmental studies have demonstrated that cognitive processes such as attention, suppression of interference and memory develop throughout childhood and adolescence. However, little is currently known about the development of top-down control mechanisms and their influence on cognitive performance. In the present study, we used functional…

Role of maternal thyroid hormones in the developing neocortex and during human evolution

PubMed Central

Stenzel, Denise; Huttner, Wieland B.

2013-01-01

The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones. PMID:23882187

Environmental Enrichment Improves Behavior, Cognition, and Brain Functional Markers in Young Senescence-Accelerated Prone Mice (SAMP8).

PubMed

Griñan-Ferré, Christian; Pérez-Cáceres, David; Gutiérrez-Zetina, Sofía Martínez; Camins, Antoni; Palomera-Avalos, Verónica; Ortuño-Sahagún, Daniel; Rodrigo, M Teresa; Pallàs, M

2016-05-01

The environment in which organisms live can greatly influence their development. Consequently, environmental enrichment (EE) is progressively recognized as an important component in the improvement of brain function and development. It has been demonstrated that rodents raised under EE conditions exhibit favorable neuroanatomical effects that improve their learning, spatial memory, and behavioral performance. Here, by using senescence-accelerated prone mice (SAMP8) and these as a model of adverse genetic conditions for brain development, we determined the effect of EE by raising these mice during early life under favorable conditions. We found a better generalized performance of SAMP8 under EE in the results of four behavioral and learning tests. In addition, we demonstrated broad molecular correlation in the hippocampus by an increase in NeuN and Ki67 expression, as well as an increase in the expression of neurotrophic factors, such as pleiotrophin (PTN) and brain-derived neurotrophic factor (BDNF), with a parallel decrease in neurodegenerative markers such as GSK3, amyloid-beta precursor protein, and phosphorylated beta-catenin, and a reduction of SBDP120, Bax, GFAP, and interleukin-6 (IL-6), resulting in a neuroprotective panorama. Globally, it can be concluded that EE applied to SAMP8 at young ages resulted in epigenetic regulatory mechanisms that give rise to significant beneficial effects at the molecular, cellular, and behavioral levels during brain development, particularly in the hippocampus.

Transcriptome assembly and candidate genes involved in nutritional programming in the swordtail fish Xiphophorus multilineatus.

PubMed

Lu, Yuan; Klimovich, Charlotte M; Robeson, Kalen Z; Boswell, William; Ríos-Cardenas, Oscar; Walter, Ronald B; Morris, Molly R

2017-01-01

Nutritional programming takes place in early development. Variation in the quality and/or quantity of nutrients in early development can influence long-term health and viability. However, little is known about the mechanisms of nutritional programming. The live-bearing fish Xiphophorus multilineatus has the potential to be a new model for understanding these mechanisms, given prior evidence of nutritional programming influencing behavior and juvenile growth rate. We tested the hypotheses that nutritional programming would influence behaviors involved in energy homeostasis as well gene expression in X. multilineatus. We first examined the influence of both juvenile environment (varied in nutrition and density) and adult environment (varied in nutrition) on behaviors involved in energy acquisition and energy expenditure in adult male X. multilineatus . We also compared the behavioral responses across the genetically influenced size classes of males. Males stop growing at sexual maturity, and the size classes of can be identified based on phenotypes (adult size and pigment patterns). To study the molecular signatures of nutritional programming, we assembled a de novo transcriptome for X. multilineatus using RNA from brain, liver, skin, testis and gonad tissues, and used RNA-Seq to profile gene expression in the brains of males reared in low quality (reduced food, increased density) and high quality (increased food, decreased density) juvenile environments. We found that both the juvenile and adult environments influenced the energy intake behavior, while only the adult environment influenced energy expenditure. In addition, there were significant interactions between the genetically influenced size classes and the environments that influenced energy intake and energy expenditure, with males from one of the four size classes (Y-II) responding in the opposite direction as compared to the other males examined. When we compared the brains of males of the Y-II size class reared in a low quality juvenile environment to males from the same size class reared in high quality juvenile environment, 131 genes were differentially expressed, including metabolism and appetite master regulator agrp gene. Our study provides evidence for nutritional programming in X. multilineatus , with variation across size classes of males in how juvenile environment and adult diet influences behaviors involved in energy homeostasis. In addition, we provide the first transcriptome of X. multilineatus , and identify a group of candidate genes involved in nutritional programming.

Early brain development toward shaping of human mind: an integrative psychoneurodevelopmental model in prenatal and perinatal medicine.

PubMed

Hruby, Radovan; Maas, Lili M; Fedor-Freybergh, P G

2013-01-01

The article introduces an integrative psychoneurodevelopmental model of complex human brain and mind development based on the latest findings in prenatal and perinatal medicine in terms of integrative neuroscience. The human brain development is extraordinarily complex set of events and could be influenced by a lot of factors. It is supported by new insights into the early neuro-ontogenic processes with the help of structural 3D magnetic resonance imaging or diffusion tensor imaging of fetal human brain. Various factors and targets for neural development including birth weight variability, fetal and early-life programming, fetal neurobehavioral states and fetal behavioral responses to various stimuli and others are discussed. Molecular biology reveals increasing sets of genes families as well as transcription and neurotropic factors together with critical epigenetic mechanisms to be deeply employed in the crucial neurodevelopmental events. Another field of critical importance is psychoimmuno-neuroendocrinology. Various effects of glucocorticoids as well as other hormones, prenatal stress and fetal HPA axis modulation are thought to be of special importance for brain development. The early postnatal period is characterized by the next intense shaping of complex competences, induced mainly by the very unique mother - newborn´s interactions and bonding. All these mechanisms serve to shape individual human mind with complex abilities and neurobehavioral strategies. Continuous research elucidating these special competences of human fetus and newborn/child supports integrative neuroscientific approach to involve various scientific disciplines for the next progress in human brain and mind research, and opens new scientific challenges and philosophic attitudes. New findings and approaches in this field could establish new methods in science, in primary prevention and treatment strategies, and markedly contribute to the development of modern integrative and personalized medicine.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

PubMed Central

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

Cognitive Developmental Biology: History, Process and Fortune's Wheel

ERIC Educational Resources Information Center

Balaban, Evan

2006-01-01

Biological contributions to cognitive development continue to be conceived predominantly along deterministic lines, with proponents of different positions arguing about the preponderance of gene-based versus experience-based influences that organize brain circuits irreversibly during prenatal or early postnatal life, and evolutionary influences…

Tissue mechanics regulate brain development, homeostasis and disease

PubMed Central

Barnes, J. Matthew

2017-01-01

ABSTRACT All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells – for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer. PMID:28043968

Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury.

PubMed

Reinert, Michael; Schaller, Benoit; Widmer, Hans Rudolf; Seiler, Rolf; Bullock, Ross

2004-08-01

Severe traumatic brain injury (TBI) imposes a huge metabolic load on brain tissue, which can be summarized initially as a state of hypermetabolism and hyperglycolysis. In experiments O2 consumption has been shown to increase early after trauma, especially in the presence of high lactate levels and forced O2 availability. In recent clinical studies the effect of increasing O2 availability on brain metabolism has been analyzed. By their nature, however, clinical trauma models suffer from a heterogeneous injury distribution. The aim of this study was to analyze, in a standardized diffuse brain injury model, the effect of increasing the fraction of inspired O2 on brain glucose and lactate levels, and to compare this effect with the metabolism of the noninjured sham-operated brain. A diffuse severe TBI model developed by Foda and Maramarou, et al., in which a 420-g weight is dropped from a height of 2 m was used in this study. Forty-one male Wistar rats each weighing approximately 300 g were included. Anesthesized rats were monitored by placing a femoral arterial line for blood pressure and blood was drawn for a blood gas analysis. Two time periods were defined: Period A was defined as preinjury and Period B as postinjury. During Period B two levels of fraction of inspired oxygen (FiO2) were studied: air (FiO2 0.21) and oxygen (FiO2 1). Four groups were studied including sham-operated animals: air-air-sham (AAS); air-O2-sham (AOS); air-air-trauma (AAT); and air-O2-trauma (AOT). In six rats the effect of increasing the FiO2 on serum glucose and lactate was analyzed. During Period B lactate values in the brain determined using microdialysis were significantly lower (p < 0.05) in the AOT group than in the AAT group and glucose values in the brain determined using microdialysis were significantly higher (p < 0.04). No differences were demonstrated in the other groups. Increasing the FiO2 had no significant effect on the serum levels of glucose and lactate. Increasing the FiO2 influences dialysate glucose and lactate levels in injured brain tissue. Using an FiO2 of 1 influences brain metabolism in such a way that lactate is significantly reduced and glucose significantly increased. No changes in dialysate glucose and lactate values were found in the noninjured brain.

In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

PubMed

Boveris, A; Llesuy, S; Azzalis, L A; Giavarotti, L; Simon, K A; Junqueira, V B; Porta, E A; Videla, L A; Lissi, E A

1997-09-19

The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

Vulnerability of children and the developing brain to neurotoxic hazards.

PubMed

Weiss, B

2000-06-01

For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.

Blood pressure and cerebral white matter share common genetic factors in Mexican Americans.

PubMed

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2011-02-01

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.

Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican-Americans

PubMed Central

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2010-01-01

Elevated arterial pulse pressure (PP) and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially due to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy (FA) of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican-Americans. The patterns of whole-brain and regional genetic overlap between BP and FA were interpreted in the context the pulse-wave encephalopathy (PWE) theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3mm, 55 directions) diffusion tensor imaging (DTI) data were analyzed for 332 (202 females; mean age=47.9±13.3years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements [PP, systolic (SBP) and diastolic (DBP)] and FA (whole-brain and regional values). Intersubject variance in PP and SBP exhibited a significant genetic overlap with variance in whole-brain FA values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=−.75, p=0.01). The pattern of genetic overlap between BP and WM integrity was generally in-agreement with the PWE theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development suggesting a possible role for genotype-by-age interactions. PMID:21135356

[Asymmetry of brain lesions and immunobiologic reactivity].

PubMed

Semenov, S F; Chuprikov, A P

1975-01-01

The authors compare some clinico-psychopathological traits in the development and frequency of detected antibrain antibodies and allergical states in epilepsy with a different lateralization in the hemispheres. In a sinistral localization of the lesion there is a significant increase of an unfavourable development of the disease and a more frequent detection of antibodies to the homologous brain. In a dextral localization there is a relatively favourable development of the basic disorder. The authors discuss the influence of the sex factor on the immunobiological indices and the lateralization of the hemisphere. A theory is suggested that the left and right hemispheres are involved in different ways in the different links of immunity, and their pathology may provoke different changes in the body reactivity.

Brain imaging in the context of food perception and eating.

PubMed

Hollmann, Maurice; Pleger, Burkhard; Villringer, Arno; Horstmann, Annette

2013-02-01

Eating behavior depends heavily on brain function. In recent years, brain imaging has proved to be a powerful tool to elucidate brain function and brain structure in the context of eating. In this review, we summarize recent findings in the fast growing body of literature in the field and provide an overview of technical aspects as well as the basic brain mechanisms identified with imaging. Furthermore, we highlight findings linking neural processing of eating-related stimuli with obesity. The consumption of food is based on a complex interplay between homeostatic and hedonic mechanisms. Several hormones influence brain activity to regulate food intake and interact with the brain's reward circuitry, which is partly mediated by dopamine signaling. Additionally, it was shown that food stimuli trigger cognitive control mechanisms that incorporate internal goals into food choice. The brain mechanisms observed in this context are strongly influenced by genetic factors, sex and personality traits. Overall, a complex picture arises from brain-imaging findings, because a multitude of factors influence human food choice. Although several key mechanisms have been identified, there is no comprehensive model that is able to explain the behavioral observations to date. Especially a careful characterization of patients according to genotypes and phenotypes could help to better understand the current and future findings in neuroimaging studies.

Brain functional connectivity changes in children that differ in impulsivity temperamental trait

PubMed Central

Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V.; García-Santos, Jose M.; Fuentes, Luis J.

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior. PMID:24834038

Brain functional connectivity changes in children that differ in impulsivity temperamental trait.

PubMed

Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V; García-Santos, Jose M; Fuentes, Luis J

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals.

PubMed

Sarkar, Amar; Lehto, Soili M; Harty, Siobhán; Dinan, Timothy G; Cryan, John F; Burnet, Philip W J

2016-11-01

Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut-brain signalling mechanisms enabling psychobiotic effects, such as metabolite production. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Estrogens of multiple classes and their role in mental health disease mechanisms.

PubMed

Watson, Cheryl S; Alyea, Rebecca A; Cunningham, Kathryn A; Jeng, Yow-Jiun

2010-08-09

Gender and sex hormones can influence a variety of mental health states, including mood, cognitive development and function, and vulnerability to neurodegenerative diseases and brain damage. Functions of neuronal cells may be altered by estrogens depending upon the availability of different physiological estrogenic ligands; these ligands and their effects vary with life stages, the genetic or postgenetic regulation of receptor levels in specific tissues, or the intercession of competing nonphysiological ligands (either intentional or unintentional, beneficial to health or not). Here we review evidence for how different estrogens (physiological and environmental/dietary), acting via different estrogen receptor subtypes residing in alternative subcellular locations, influence brain functions and behavior. We also discuss the families of receptors and transporters for monoamine neurotransmitters and how they may interact with the estrogenic signaling pathways.

At risk of being risky: The relationship between "brain age" under emotional states and risk preference.

PubMed

Rudolph, Marc D; Miranda-Domínguez, Oscar; Cohen, Alexandra O; Breiner, Kaitlyn; Steinberg, Laurence; Bonnie, Richard J; Scott, Elizabeth S; Taylor-Thompson, Kim; Chein, Jason; Fettich, Karla C; Richeson, Jennifer A; Dellarco, Danielle V; Galván, Adriana; Casey, B J; Fair, Damien A

2017-04-01

Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10-25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the "brain age" of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that "brain age" across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception - a pattern exemplified greatest in young-adults (ages 18-21). The results are suggestive of a specified functional brain phenotype that relates to being at "risk to be risky." Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Does gender matter? Differences in social-emotional behavior among infants and toddlers before and after mild traumatic brain injury: a preliminary study.

PubMed

Kaldoja, Mari-Liis; Kolk, Anneli

2015-06-01

Traumatic brain injury is a common cause of acquired disability in childhood. While much is known about cognitive sequelae of brain trauma, gender-specific social-emotional problems in children with mild traumatic brain injury is far less understood. The aims of the study were to investigate gender differences in social-emotional behavior before and after mild traumatic brain injury. Thirty-five 3- to 65-month-old children with mild traumatic brain injury and 70 controls were assessed with Ages and Stages Questionnaires: Social-Emotional. Nine months later, 27 of 35 patients and 54 of 70 controls were reassessed. We found that before injury, boys had more self-regulation and autonomy difficulties and girls had problems with adaptive functioning. Nine months after injury, boys continued to struggle with self-regulation and autonomy and new difficulties with interaction had emerged, whereas in girls, problems in interaction had evolved. Even mild traumatic brain injury in early childhood disrupts normal social-emotional development having especially devastating influence on interaction skills. © The Author(s) 2014.

At risk of being risky: the relationship between “brain age” under emotional states and risk preference

PubMed Central

Rudolph, Marc D.; Miranda-Dominguez, Oscar; Cohen, Alexandra O.; Breiner, Kaitlyn; Steinberg, Laurence; Bonnie, Richard J.; Scott, Elizabeth S.; Taylor-Thompson, Kim A.; Chein, Jason; Fettich, Karla C.; Richeson, Jennifer A.; Dellarco, Danielle V.; Galván, Adriana; Casey, BJ; Fair, Damien A.

2017-01-01

Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10–25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the “brain age” of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that “brain age” across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception – a pattern exemplified greatest in young-adults (ages 18–21). The results are suggestive of a specified functional brain phenotype that relates to being at “risk to be risky.” PMID:28279917

Effect of alternate energy substrates on mammalian brain metabolism during ischemic events.

PubMed

Koppaka, S S; Puchowicz; LaManna, J C; Gatica, J E

2008-01-01

Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.

Visual artistic creativity and the brain.

PubMed

Heilman, Kenneth M; Acosta, Lealani Mae

2013-01-01

Creativity is the development of a new or novel understanding--insight that leads to the expression of orderly relationships (e.g., finding and revealing the thread that unites). Visual artistic creativity plays an important role in the quality of human lives, and the goal of this chapter is to describe some of the brain mechanisms that may be important in visual artistic creativity. The initial major means of learning how the brain mediates any activity is to understand the anatomy and physiology that may support these processes. A further understanding of specific cognitive activities and behaviors may be gained by studying patients who have diseases of the brain and how these diseases influence these functions. Physiological recording such as electroencephalography and brain imaging techniques such as PET and fMRI have also allowed us to gain a better understanding of the brain mechanisms important in visual creativity. In this chapter, we discuss anatomic and physiological studies, as well as neuropsychological studies of healthy artists and patients with neurological disease that have helped us gain some insight into the brain mechanisms that mediate artistic creativity. © 2013 Elsevier B.V. All rights reserved.

The development of neural correlates for memory formation

PubMed Central

Ofen, Noa

2012-01-01

A growing body of literature considers the development of episodic memory systems in the brain; the majority are neuroimaging studies conducted during memory encoding in order to explore developmental trajectories in memory formation. This review considers evidence from behavioral studies of memory development, neural correlates of memory formation in adults, and structural brain development, all of which form the foundation of a developmental cognitive neuroscience approach to memory development. I then aim to integrate the current evidence from developmental functional neuroimaging studies of memory formation with respect to three hypotheses. First, memory development reflects the development in the use of memory strategies, linked to prefrontal cortex. Second, developmental effects within the medial temporal lobes are more complex, and correspond to current notions about the nature in which the MTL support the formation of memory. Third, neurocognitive changes in content representation influence memory. Open issues and current directions are discussed. PMID:22414608

The "chicken-and-egg" development of political opinionsThe roles of genes, social status, ideology, and information.

PubMed

Peter, Beattie J D

2017-01-01

Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a "chicken-and-egg" question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.

Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

PubMed

Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

2016-09-01

The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

Alpha shape theory for 3D visualization and volumetric measurement of brain tumor progression using magnetic resonance images.

PubMed

Hamoud Al-Tamimi, Mohammed Sabbih; Sulong, Ghazali; Shuaib, Ibrahim Lutfi

2015-07-01

Resection of brain tumors is a tricky task in surgery due to its direct influence on the patients' survival rate. Determining the tumor resection extent for its complete information via-à-vis volume and dimensions in pre- and post-operative Magnetic Resonance Images (MRI) requires accurate estimation and comparison. The active contour segmentation technique is used to segment brain tumors on pre-operative MR images using self-developed software. Tumor volume is acquired from its contours via alpha shape theory. The graphical user interface is developed for rendering, visualizing and estimating the volume of a brain tumor. Internet Brain Segmentation Repository dataset (IBSR) is employed to analyze and determine the repeatability and reproducibility of tumor volume. Accuracy of the method is validated by comparing the estimated volume using the proposed method with that of gold-standard. Segmentation by active contour technique is found to be capable of detecting the brain tumor boundaries. Furthermore, the volume description and visualization enable an interactive examination of tumor tissue and its surrounding. Admirable features of our results demonstrate that alpha shape theory in comparison to other existing standard methods is superior for precise volumetric measurement of tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

The influence of complex and threatening environments in early life on brain size and behaviour.

PubMed

DePasquale, C; Neuberger, T; Hirrlinger, A M; Braithwaite, V A

2016-01-27

The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. © 2016 The Authors.

The influence of complex and threatening environments in early life on brain size and behaviour

PubMed Central

Neuberger, T.; Hirrlinger, A. M.; Braithwaite, V. A.

2016-01-01

The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. PMID:26817780

Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics

PubMed Central

Bollig-Fischer, Aliccia; Michelhaugh, Sharon K.; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

2015-01-01

Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n=4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments. PMID:25970776

Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

PubMed

Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

2015-06-10

Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

The neurobiology of emotion–cognition interactions: fundamental questions and strategies for future research

PubMed Central

Okon-Singer, Hadas; Hendler, Talma; Pessoa, Luiz; Shackman, Alexander J.

2015-01-01

Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the ‘emotional’ and the ‘cognitive’ brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of ‘the emotional brain’ and ‘the cognitive brain’ are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders. PMID:25774129

Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus.

PubMed

Sandman, Curt A; Davis, Elysia P; Buss, Claudia; Glynn, Laura M

2012-01-01

Accumulating evidence from a relatively small number of prospective studies indicates that exposure to prenatal stress profoundly influences the developing human fetus with consequences that persist into childhood and very likely forever. Maternal/fetal dyads are assessed at ∼20, ∼25, ∼31 and ∼36 weeks of gestation. Infant assessments begin 24 h after delivery with the collection of cortisol and behavioral responses to the painful stress of the heel-stick procedure and measures of neonatal neuromuscular maturity. Infant cognitive, neuromotor development, stress and emotional regulation are evaluated at 3, 6 12 and 24 months of age. Maternal psychosocial stress and demographic information is collected in parallel with infant assessments. Child neurodevelopment is assessed with cognitive tests, measures of adjustment and brain imaging between 5 and 8 years of age. Psychobiological markers of stress during pregnancy, especially early in gestation, result in delayed fetal maturation, disrupted emotional regulation and impaired cognitive performance during infancy and decreased brain volume in areas associated with learning and memory in 6- to 8-year-old children. We review findings from our projects that maternal endocrine alterations that accompany pregnancy and influence fetal/infant/child development are associated with decreased affective responses to stress, altered memory function and increased risk for postpartum depression. Our findings indicate that the mother and her fetus both are influenced by exposure to psychosocial and biological stress. The findings that fetal and maternal programming occur in parallel may have important implications for long-term child development and mother/child interactions. Copyright © 2011 S. Karger AG, Basel.

Gene expression in the aging human brain: an overview.

PubMed

Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

2016-03-01

The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

Structure and function of the healthy pre-adolescent pediatric gut microbiome

USDA-ARS?s Scientific Manuscript database

The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limite...

Testosterone affects language areas of the adult human brain

PubMed Central

Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

2016-01-01

Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

SOCIAL: an integrative framework for the development of social skills.

PubMed

Beauchamp, Miriam H; Anderson, Vicki

2010-01-01

Despite significant advances in the field of social neuroscience, much remains to be understood regarding the development and maintenance of social skills across the life span. Few comprehensive models exist that integrate multidisciplinary perspectives and explain the multitude of factors that influence the emergence and expression of social skills. Here, a developmental biopsychosocial model (SOCIAL) is offered that incorporates the biological underpinnings and socio-cognitive skills that underlie social function (attention/executive function, communication, socio-emotional skills), as well as the internal and external (environmental) factors that mediate these skills. The components of the model are discussed in the context of the social brain network and are supported by evidence from 3 conditions known to affect social functioning (autism spectrum disorders, schizophrenia, and traumatic brain injury). This integrative model is intended to provide a theoretical structure for understanding the origins of social dysfunction and the factors that influence the emergence of social skills through childhood and adolescence in both healthy and clinical populations.

Memory Retrieval in Mice and Men

PubMed Central

Ben-Yakov, Aya; Dudai, Yadin; Mayford, Mark R.

2015-01-01

Retrieval, the use of learned information, was until recently mostly terra incognita in the neurobiology of memory, owing to shortage of research methods with the spatiotemporal resolution required to identify and dissect fast reactivation or reconstruction of complex memories in the mammalian brain. The development of novel paradigms, model systems, and new tools in molecular genetics, electrophysiology, optogenetics, in situ microscopy, and functional imaging, have contributed markedly in recent years to our ability to investigate brain mechanisms of retrieval. We review selected developments in the study of explicit retrieval in the rodent and human brain. The picture that emerges is that retrieval involves coordinated fast interplay of sparse and distributed corticohippocampal and neocortical networks that may permit permutational binding of representational elements to yield specific representations. These representations are driven largely by the activity patterns shaped during encoding, but are malleable, subject to the influence of time and interaction of the existing memory with novel information. PMID:26438596

Nitric Oxide in the Crustacean Brain: Regulation of Neurogenesis and Morphogenesis in the Developing Olfactory Pathway

PubMed Central

Benton, J.L.; Sandeman, D.C.; Beltz, B.S.

2009-01-01

Nitric oxide (NO) plays major roles during development and in adult organisms. We examined the temporal and spatial patterns of nitric oxide synthase (NOS) appearance in the embryonic lobster brain to localize sources of NO activity; potential NO targets were identified by defining the distribution of NO-induced cGMP. Staining patterns are compared with NOS and cyclic 3,5 guanosine monophosphate (cGMP) distribution in adult lobster brains. Manipulation of NO levels influences olfactory glomerular formation and stabilization, as well as levels of neurogenesis among the olfactory projection neurons. In the first 2 days following ablation of the lateral antennular flagella in juvenile lobsters, a wave of increased NOS immunoreactivity and a reduction in neurogenesis occur. These studies implicate nitric oxide as a developmental architect and also support a role for this molecule in the neural response to injury in the olfactory pathway. PMID:17948307

Peer Influence Via Instagram: Effects on Brain and Behavior in Adolescence and Young Adulthood.

PubMed

Sherman, Lauren E; Greenfield, Patricia M; Hernandez, Leanna M; Dapretto, Mirella

2018-01-01

Mobile social media often feature the ability to "Like" content posted by others. This study examined the effect of Likes on youths' neural and behavioral responses to photographs. High school and college students (N = 61, ages 13-21) viewed theirs and others' Instagram photographs while undergoing functional Magnetic Resonance Imaging (fMRI). Participants more often Liked photographs that appeared to have received many (vs. few) Likes. Popular photographs elicited greater activity in multiple brain regions, including the nucleus accumbens (NAcc), a hub of the brain's reward circuitry. NAcc responsivity increased with age for high school but not college students. When viewing images depicting risk-taking (vs. nonrisky photographs), high school students, but not college students, showed decreased activation of neural regions implicated in cognitive control. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

The biopsychosocial approach to chronic pain: scientific advances and future directions.

PubMed

Gatchel, Robert J; Peng, Yuan Bo; Peters, Madelon L; Fuchs, Perry N; Turk, Dennis C

2007-07-01

The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment, and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors, is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness as well as on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms. Copyright 2007 APA

The social brain in adolescence: Evidence from functional magnetic resonance imaging and behavioural studies

PubMed Central

Burnett, Stephanie; Sebastian, Catherine; Kadosh, Kathrin Cohen; Blakemore, Sarah-Jayne

2015-01-01

Social cognition is the collection of cognitive processes required to understand and interact with others. The term ‘social brain’ refers to the network of brain regions that underlies these processes. Recent evidence suggests that a number of social cognitive functions continue to develop during adolescence, resulting in age differences in tasks that assess cognitive domains including face processing, mental state inference and responding to peer influence and social evaluation. Concurrently, functional and structural magnetic resonance imaging (MRI) studies show differences between adolescent and adult groups within parts of the social brain. Understanding the relationship between these neural and behavioural observations is a challenge. This review discusses current research findings on adolescent social cognitive development and its functional MRI correlates, then integrates and interprets these findings in the context of hypothesised developmental neurocognitive and neurophysiological mechanisms. PMID:21036192

Early life influences on emotional reactivity: evidence that social enrichment has greater effects than handling on anxiety-like behaviors, neuroendocrine responses to stress and central BDNF levels.

PubMed

Cirulli, Francesca; Berry, Alessandra; Bonsignore, Luca Tommaso; Capone, Francesca; D'Andrea, Ivana; Aloe, Luigi; Branchi, Igor; Alleva, Enrico

2010-05-01

During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations. (c) 2010 Elsevier Ltd. All rights reserved.

Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

PubMed

Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

2018-03-28

Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

PubMed

Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

2016-01-01

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

Preterm birth and maternal responsiveness during childhood are associated with brain morphology in adolescence.

PubMed

Frye, Richard E; Malmberg, Benjamin; Swank, Paul; Smith, Karen; Landry, Susan

2010-09-01

Although supportive parenting has been shown to have positive effects on development, the neurobiological basis of supportive parenting has not been investigated. Thirty-three adolescents were systemically selected from a longitudinal study on child development based on maternal responsiveness during childhood, a measure of supportive parenting, and whether they were born term or preterm. We analyzed the effect of preterm birth on hemispheric and regional (frontal, temporal, parietal) cortical thickness and surface area using mixed-model analysis while also considering the effect of brain hemisphere (left vs. right). We then determined whether these factors were moderated by maternal responsiveness during childhood. Preterm birth was associated with regional and hemispheric differences in cortical thickness and surface area. Maternal responsiveness during childhood moderated hemispheric cortical thickness. Adolescence with mothers that were inconsistently responsive during childhood demonstrated greater overall cortical thickness and greater asymmetry in cortical thickness during adolescence as compared to adolescence with mothers who were consistently responsive or unresponsive during childhood. Maternal responsiveness and preterm birth did not interact. These data suggest that changes in brain morphology associated with preterm birth continue into adolescence and support the notion that the style of maternal-child interactions during childhood influence brain development into adolescence.

Resilience in mathematics after early brain injury: The roles of parental input and early plasticity.

PubMed

Glenn, Dana E; Demir-Lira, Özlem Ece; Gibson, Dominic J; Congdon, Eliza L; Levine, Susan C

2018-04-01

Children with early focal unilateral brain injury show remarkable plasticity in language development. However, little is known about how early brain injury influences mathematical learning. Here, we examine early number understanding, comparing cardinal number knowledge of typically developing children (TD) and children with pre- and perinatal lesions (BI) between 42 and 50 months of age. We also examine how this knowledge relates to the number words children hear from their primary caregivers early in life. We find that children with BI, are, on average, slightly behind TD children in both cardinal number knowledge and later mathematical performance, and show slightly slower learning rates than TD children in cardinal number knowledge during the preschool years. We also find that parents' "number talk" to their toddlers predicts later mathematical ability for both TD children and children with BI. These findings suggest a relatively optimistic story in which neural plasticity is at play in children's mathematical development following early brain injury. Further, the effects of early number input suggest that intervening to enrich the number talk that children with BI hear during the preschool years could narrow the math achievement gap. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Singing-driven gene expression in the developing songbird brain

PubMed Central

Johnson, Frank; Whitney, Osceola

2014-01-01

Neural and behavioral development arises from an integration of genetic and environmental influences, yet specifying the nature of this interaction remains a primary problem in neuroscience. Here, we review molecular and behavioral studies that focus on the role of singing-driven gene expression during neural and vocal development in the male zebra finch (Taeniopygia guttata), a songbird that learns a species-typical vocal pattern during juvenile development by imitating an adult male tutor. A primary aim of our lab has been to identify naturally-occurring environmental influences that shape the propensity to sing. This ethological approach underlies our theoretical perspective, which is to integrate the significance of singing-driven gene expression into a broader ecological context. PMID:16129463

Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on foetal guinea pig brain development.

PubMed

Kelleher, Meredith A; Palliser, Hannah K; Walker, David W; Hirst, Jonathan J

2011-03-01

Progesterone and its neuroactive metabolite, allopregnanolone, are present in high concentrations during pregnancy, but drop significantly following birth. Allopregnanolone influences foetal arousal and enhances cognitive and behavioural recovery following traumatic brain injury. Inhibition of allopregnanolone synthesis increases cell death in foetal animal brains with experimental hypoxia. We hypothesised that complications during pregnancy, such as early or preterm loss of placental steroids and intrauterine growth restriction (IUGR), would disrupt the foetal neurosteroid system, contributing to poor neurodevelopmental outcomes. This study aimed to investigate the effects of chronic inhibition of allopregnanolone synthesis before term and IUGR on developmental processes in the foetal brain. Guinea pig foetuses were experimentally growth restricted at mid-gestation and treated with finasteride, an inhibitor of allopregnanolone synthesis. Finasteride treatment reduced foetal brain allopregnanolone concentrations by up to 75% and was associated with a reduction in myelin basic protein (MBP) (P = 0.001) and an increase in glial fibrillary acidic protein expression in the subcortical white matter brain region (P < 0.001). IUGR resulted in decreased MBP expression (P < 0.01) and was associated with a reduction in the expression of steroidogenic enzyme 5α-reductase (5αR) type 2 in the foetal brain (P = 0.061). Brain levels of 5αR1 were higher in male foetuses (P = 0.008). Both IUGR and reduced foetal brain concentrations of allopregnanolone were associated with altered expression of myelination and glial cell markers within the developing foetal brain. The potential role of neurosteroids in protecting and regulating neurodevelopmental processes in the foetal brain may provide new directions for treatment of neurodevelopmental disorders in infants who are exposed to perinatal insults and pathologies.

Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth

PubMed Central

Aubert-Broche, Bérengère; Fonov, Vladimir; Narayanan, Sridar; Arnold, Douglas L.; Araujo, David; Fetco, Dumitru; Till, Christine; Sled, John G.; Collins, D. Louis

2014-01-01

Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. PMID:25378667

Dermatoglyphics in relation to brain volumes in twins concordant and discordant for bipolar disorder.

PubMed

Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S

2014-12-01

Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature.

PubMed

Carnevale, Daniela; Mascio, Giada; D'Andrea, Ivana; Fardella, Valentina; Bell, Robert D; Branchi, Igor; Pallante, Fabio; Zlokovic, Berislav; Yan, Shirley Shidu; Lembo, Giuseppe

2012-07-01

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.

Model of brain activation predicts the neural collective influence map of the brain

PubMed Central

Morone, Flaviano; Roth, Kevin; Min, Byungjoon; Makse, Hernán A.

2017-01-01

Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory. PMID:28351973

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis.

PubMed

Jenkins, Trisha A; Nguyen, Jason C D; Polglaze, Kate E; Bertrand, Paul P

2016-01-20

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

Mapping the Regional Influence of Genetics on Brain Structure Variability - A Tensor-Based Morphometry Study

PubMed Central

Brun, Caroline; Leporé, Natasha; Pennec, Xavier; Lee, Agatha D.; Barysheva, Marina; Madsen, Sarah K.; Avedissian, Christina; Chou, Yi-Yu; de Zubicaray, Greig I.; McMahon, Katie; Wright, Margaret; Toga, Arthur W.; Thompson, Paul M.

2010-01-01

Genetic and environmental factors influence brain structure and function profoundly The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins’ 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject’s anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions which have a more protracted maturational time-course. PMID:19446645

Scalp and skull influence on near infrared photon propagation in the Colin27 brain template.

PubMed

Strangman, Gary E; Zhang, Quan; Li, Zhi

2014-01-15

Near-infrared neuromonitoring (NIN) is based on near-infrared spectroscopy (NIRS) measurements performed through the intact scalp and skull. Despite the important effects of overlying tissue layers on the measurement of brain hemodynamics, the influence of scalp and skull on NIN sensitivity are not well characterized. Using 3555 Monte Carlo simulations, we estimated the sensitivity of individual continuous-wave NIRS measurements to brain activity over the entire adult human head by introducing a small absorption perturbation to brain gray matter and quantifying the influence of scalp and skull thickness on this sensitivity. After segmenting the Colin27 template into five tissue types (scalp, skull, cerebrospinal fluid, gray matter and white matter), the average scalp thickness was 6.9 ± 3.6 mm (range: 3.6-11.2mm), while the average skull thickness was 6.0 ± 1.9 mm (range: 2.5-10.5mm). Mean NIN sensitivity - defined as the partial path length through gray matter divided by the total photon path length - ranged from 0.06 (i.e., 6% of total path length) at a 20mm source-detector separation, to over 0.19 at 50mm separations. NIN sensitivity varied substantially around the head, with occipital pole exhibiting the highest NIRS sensitivity to gray matter, whereas inferior frontal regions had the lowest sensitivity. Increased scalp and skull thickness were strongly associated with decreased sensitivity to brain tissue. Scalp thickness always exhibited a slightly larger effect on sensitivity than skull thickness, but the effect of both varied with SD separation. We quantitatively characterize sensitivity around the head as well as the effects of scalp and skull, which can be used to interpret NIN brain activation studies as well as guide the design, development and optimization of NIRS devices and sensors. Copyright © 2013 Elsevier Inc. All rights reserved.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational methodologies. Because early-life adversity is a powerful determinant of subsequent vulnerabilities to emotional and cognitive pathologies, understanding the underlying processes will have profound implications for the world's current and future children.

Primary cultures of astrocytes from fetal bovine brain.

PubMed

Ballarin, Cristina; Peruffo, Antonella

2012-01-01

We describe here a method to obtain primary cell cultures from the cerebral cortex and the hypothalamus of bovine fetuses. We report how tissue origin, developmental stages, and culture medium conditions influence cell differentiation and the prevalence of glial cells vs. neurons. We compare explants from early, middle, and late stages of development and two different fetal calf serum concentrations (1 and 10%) to identify the best conditions to obtain and grow viable astrocytes in culture. In addition, we describe how to cryopreserve and obtain viable cortical astrocytes from frozen fetal bovine brain samples.

Sculpting the brain

PubMed Central

Garcia-Lopez, Pablo

2012-01-01

Neuroculture, conceived as the reciprocal interaction between neuroscience and different areas of human knowledge is influencing our lives under the prism of the latest neuroscientific discoveries. Simultaneously, neuroculture can create new models of thinking that can significantly impact neuroscientists' daily practice. Especially interesting is the interaction that takes place between neuroscience and the arts. This interaction takes place at different, infinite levels and contexts. I contextualize my work inside this neurocultural framework. Through my artwork, I try to give a more natural vision of the human brain, which could help to develop a more humanistic culture. PMID:22363275

How emotional abilities modulate the influence of early life stress on hippocampal functioning.

PubMed

Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

2014-07-01

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Direct and Indirect Effects of Brain Volume, Socioeconomic Status and Family Stress on Child IQ

PubMed Central

Marcus Jenkins, Jade V; Woolley, Donald P; Hooper, Stephen R; De Bellis, Michael D

2013-01-01

1.1. Background A large literature documents the detrimental effects of socioeconomic disparities on intelligence and neuropsychological development. Researchers typically measure environmental factors such as socioeconomic status (SES), using income, parent's occupation and education. However, SES is more complex, and this complexity may influence neuropsychological outcomes. 1.2. Methods This studyused principal components analysis to reduce 14 SES and 28 family stress indicators into their core dimensions (e.g. community and educational capital, financial resources, marital conflict). Core dimensions were used in path analyses to examine their relationships with parent IQ and cerebral volume (white matter, grey matter and total brain volume), to predict child IQ in a sample of typically developing children. 1.3. Results Parent IQ affected child IQ directly and indirectly through community and educational capital, demonstrating how environmental factors interact with familial factors in neuro-development. There were no intervening effects of cerebral white matter, grey matter, or total brain volume. 1.4. Conclusions Findings may suggest that improving community resources can foster the intellectual development of children. PMID:24533427

Emotional Modulation of Learning and Memory: Pharmacological Implications.

PubMed

LaLumiere, Ryan T; McGaugh, James L; McIntyre, Christa K

2017-07-01

Memory consolidation involves the process by which newly acquired information becomes stored in a long-lasting fashion. Evidence acquired over the past several decades, especially from studies using post-training drug administration, indicates that emotional arousal during the consolidation period influences and enhances the strength of the memory and that multiple different chemical signaling systems participate in this process. The mechanisms underlying the emotional influences on memory involve the release of stress hormones and activation of the basolateral amygdala, which work together to modulate memory consolidation. Moreover, work suggests that this amygdala-based memory modulation occurs with numerous types of learning and involves interactions with many different brain regions to alter consolidation. Additionally, studies suggest that emotional arousal and amygdala activity in particular influence synaptic plasticity and associated proteins in downstream brain regions. This review considers the historical understanding for memory modulation and cellular consolidation processes and examines several research areas currently using this foundational knowledge to develop therapeutic treatments. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

The Impact of Traumatic Brain Injury on Later Life: Effects on Normal Aging and Neurodegenerative Diseases.

PubMed

Griesbach, Grace S; Masel, Brent E; Helvie, Richard E; Ashley, Mark J

2018-01-01

The acute and chronic effects of traumatic brain injury (TBI) have been widely described; however, there is limited knowledge on how a TBI sustained during early adulthood or mid-adulthood will influence aging. Epidemiological studies have explored whether TBI poses a risk for dementia and other neurodegenerative diseases associated with aging. We will discuss the influence of TBI and resulting medical comorbidities such as endocrine, sleep, and inflammatory disturbances on age-related gray and white matter changes and cognitive decline. Post mortem studies examining amyloid, tau, and other proteins will be discussed within the context of neurodegenerative diseases and chronic traumatic encephalopathy. The data support the suggestion that pathological changes triggered by an earlier TBI will have an influence on normal aging processes and will interact with neurodegenerative disease processes rather than the development of a specific disease, such as Alzheimer's or Parkinson's. Chronic neurophysiologic change after TBI may have detrimental effects on neurodegenerative disease.

Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

EPA Science Inventory

Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy.

PubMed

Russmann, Vera; Brendel, Matthias; Mille, Erik; Helm-Vicidomini, Angela; Beck, Roswitha; Günther, Lisa; Lindner, Simon; Rominger, Axel; Keck, Michael; Salvamoser, Josephine D; Albert, Nathalie L; Bartenstein, Peter; Potschka, Heidrun

2017-01-01

Excessive activation of inflammatory signaling pathways seems to be a hallmark of epileptogenesis. Positron emission tomography (PET) allows in vivo detection of brain inflammation with spatial information and opportunities for longitudinal follow-up scanning protocols. Here, we assessed whether molecular imaging of the 18 kDa translocator protein (TSPO) can serve as a biomarker for the development of epilepsy. Therefore, brain uptake of [ 18 F]GE-180, a highly selective radioligand of TSPO, was investigated in a longitudinal PET study in a chronic rat model of temporal lobe epilepsy. Analyses revealed that the influence of the epileptogenic insult on [ 18 F]GE-180 brain uptake was most pronounced in the earlier phase of epileptogenesis. Differences were evident in various brain regions during earlier phases of epileptogenesis with [ 18 F]GE-180 standardized uptake value enhanced by 2.1 to 2.7fold. In contrast, brain regions exhibiting differences seemed to be more restricted with less pronounced increases of tracer uptake by 1.8-2.5fold four weeks following status epilepticus and by 1.5-1.8fold in the chronic phase. Based on correlation analysis, we were able to identify regions with a predictive value showing a correlation with seizure development. These regions include the amygdala as well as a cluster of brain areas. This cluster comprises parts of different brain regions, e.g. the hippocampus, parietal cortex, thalamus, and somatosensory cortex. In conclusion, the data provide evidence that [ 18 F]GE-180 PET brain imaging can serve as a biomarker of epileptogenesis. The identification of brain regions with predictive value might facilitate the development of preventive concepts as well as the early assessment of the interventional success. Future studies are necessary to further confirm the predictivity of the approach.

Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury.

PubMed

Sahuquillo, Juan; Vilalta, Anna

2007-01-01

Neither any neuroprotective drug has been shown to be beneficial in improving the outcome of severe traumatic brain injury (TBI) nor has any prophylactically-induced moderate hypothermia shown any beneficial effect on outcome in severe TBI, despite the optimism generated by preclinical studies. This contrasts with the paradox that hypothermia still is the most powerful neuroprotective method in experimental models because of its ability to influence the multiple biochemical cascades that are set in motion after TBI. The aim of this short review is to highlight the most recent developments concerning the pathophysiology of severe TBI, to review new data on thermoregulation and induced hypothermia, the regulation of core and brain temperature in mammals and the multiplicity of effects of hypothermia in the pathophysiology of TBI. Many experimental studies in the last decade have again confirmed that moderate hypothermia confers protection against ischemic and non-ischemic brain hypoxia, traumatic brain injury, anoxic injury following resuscitation after cardiac arrest and other neurological insults. Many posttraumatic adverse events that occur in the injured brain at a cellular and molecular level are highly temperature-sensitive and are thus a good target for induced hypothermia. The basic mechanisms through which hypothermia protects the brain are clearly multifactorial and include at least the following: reduction in brain metabolic rate, effects on cerebral blood flow, reduction of the critical threshold for oxygen delivery, blockade of excitotoxic mechanisms, calcium antagonism, preservation of protein synthesis, reduction of brain thermopooling, a decrease in edema formation, modulation of the inflammatory response, neuroprotection of the white matter and modulation of apoptotic cell death. The new developments discussed in this review indicate that, by targeting many of the abnormal neurochemical cascades initiated after TBI, induced hypothermia may modulate neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in cardiac arrest and better and more reliable cooling methods have given hypothermia a second chance in treating TBI patients. A critical evaluation of hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe traumatic brain injuries.

Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.

PubMed

Caputi, Valentina; Giron, Maria Cecilia

2018-06-06

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade.

Tough times call for bigger brains

PubMed Central

Pravosudov, Vladimir V

2009-01-01

Memory is crucial for survival in many animals. Spatial memory in particular is important for food-caching species and may be influenced by selective pressures such as climate. The influence of climate on memory may be facilitated through the hippocampus (Hp), the part of the brain responsible in part for spatial memory. In a recent paper, we conducted the first large-scale test of the relationship between memory, the climate and the brain in a single food-caching species, the black-capped chickadee (Poecile atricapillus). We found that birds from more harsh northern climates had significantly larger hippocampal volumes and more neurons than those from more mild southern latitudes. This work suggests that environmental pressures are capable of influencing specific brain regions, which may result in enhanced memory, and hence survival, in harsh climates. This work gives us a better understanding of how the brain responds to different environments and how animals can adapt to their environment in general. PMID:19641741

Iron and Mechanisms of Emotional Behavior

PubMed Central

Kim, Jonghan; Wessling-Resnick, Marianne

2014-01-01

Iron is required for appropriate behavioral organization. Iron deficiency results in poor brain myelination and impaired monoamine metabolism. Glutamate and GABA homeostasis is modified by changes in brain iron status. Such changes not only produce deficits in memory/learning capacity and motor skills, but also emotional and psychological problems. An accumulating body of evidence indicates that both energy metabolism and neurotransmitter homeostasis influence emotional behavior, and both functions are influenced by brain iron status. Like other neurobehavioral aspects, the influence of iron metabolism on mechanisms of emotional behavior are multifactorial: brain region-specific control of behavior, regulation of neurotransmitters and associated proteins, temporal and regional differences in iron requirements, oxidative stress responses to excess iron, sex differences in metabolism, and interactions between iron and other metals. To better understand the role that brain iron plays in emotional behavior and mental health, this review discusses the pathologies associated with anxiety and other emotional disorders with respect to body iron status. PMID:25154570

Neurodevelopmental origins of lifespan changes in brain and cognition

PubMed Central

Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.

2016-01-01

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992

Sex-Dependent Effects of Developmental Lead Exposure on the Brain.

PubMed

Singh, Garima; Singh, Vikrant; Sobolewski, Marissa; Cory-Slechta, Deborah A; Schneider, Jay S

2018-01-01

The role of sex as an effect modifier of developmental lead (Pb) exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of human epidemiological studies have included both sexes in independent outcome analyses limiting our ability to draw definitive conclusions regarding sex-differentiated outcomes. Additionally, due to various methodological differences across studies, there is still not a good mechanistic understanding of the molecular effects of lead on the brain and the factors that influence differential responses to Pb based on sex. In this review, focused on prenatal and postnatal Pb exposures in humans and animal models, we discuss current literature supporting sex differences in outcomes in response to Pb exposure and explore some of the ideas regarding potential molecular mechanisms that may contribute to sex-related differences in outcomes from developmental Pb exposure. The sex-dependent variability in outcomes from developmental Pb exposure may arise from a combination of complex factors, including, but not limited to, intrinsic sex-specific molecular/genetic mechanisms and external risk factors including sex-specific responses to environmental stressors which may act through shared epigenetic pathways to influence the genome and behavioral output.

Sex-Dependent Effects of Developmental Lead Exposure on the Brain

PubMed Central

Singh, Garima; Singh, Vikrant; Sobolewski, Marissa; Cory-Slechta, Deborah A.; Schneider, Jay S.

2018-01-01

The role of sex as an effect modifier of developmental lead (Pb) exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of human epidemiological studies have included both sexes in independent outcome analyses limiting our ability to draw definitive conclusions regarding sex-differentiated outcomes. Additionally, due to various methodological differences across studies, there is still not a good mechanistic understanding of the molecular effects of lead on the brain and the factors that influence differential responses to Pb based on sex. In this review, focused on prenatal and postnatal Pb exposures in humans and animal models, we discuss current literature supporting sex differences in outcomes in response to Pb exposure and explore some of the ideas regarding potential molecular mechanisms that may contribute to sex-related differences in outcomes from developmental Pb exposure. The sex-dependent variability in outcomes from developmental Pb exposure may arise from a combination of complex factors, including, but not limited to, intrinsic sex-specific molecular/genetic mechanisms and external risk factors including sex-specific responses to environmental stressors which may act through shared epigenetic pathways to influence the genome and behavioral output. PMID:29662502

Genetic and environmental influences on the size of specific brain regions in midlife: the VETSA MRI study.

PubMed

Kremen, William S; Prom-Wormley, Elizabeth; Panizzon, Matthew S; Eyler, Lisa T; Fischl, Bruce; Neale, Michael C; Franz, Carol E; Lyons, Michael J; Pacheco, Jennifer; Perry, Michele E; Stevens, Allison; Schmitt, J Eric; Grant, Michael D; Seidman, Larry J; Thermenos, Heidi W; Tsuang, Ming T; Eisen, Seth A; Dale, Anders M; Fennema-Notestine, Christine

2010-01-15

The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00-0.75) as compared with subcortical and ventricular ROIs (0.48-0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.

Recommendations for Development of New Standardized Forms of Cocoa Breeds and Cocoa Extract Processing for the Prevention of Alzheimer's Disease: Role of Cocoa in Promotion of Cognitive Resilience and Healthy Brain Aging.

PubMed

Dubner, Lauren; Wang, Jun; Ho, Lap; Ward, Libby; Pasinetti, Giulio M

2015-01-01

It is currently thought that the lackluster performance of translational paradigms in the prevention of age-related cognitive deteriorative disorders, such as Alzheimer's disease (AD), may be due to the inadequacy of the prevailing approach of targeting only a single mechanism. Age-related cognitive deterioration and certain neurodegenerative disorders, including AD, are characterized by complex relationships between interrelated biological phenotypes. Thus, alternative strategies that simultaneously target multiple underlying mechanisms may represent a more effective approach to prevention, which is a strategic priority of the National Alzheimer's Project Act and the National Institute on Aging. In this review article, we discuss recent strategies designed to clarify the mechanisms by which certain brain-bioavailable, bioactive polyphenols, in particular, flavan-3-ols also known as flavanols, which are highly represented in cocoa extracts, may beneficially influence cognitive deterioration, such as in AD, while promoting healthy brain aging. However, we note that key issues to improve consistency and reproducibility in the development of cocoa extracts as a potential future therapeutic agent requires a better understanding of the cocoa extract sources, their processing, and more standardized testing including brain bioavailability of bioactive metabolites and brain target engagement studies. The ultimate goal of this review is to provide recommendations for future developments of cocoa extracts as a therapeutic agent in AD.

Delineation of separate brain regions used for scientific versus engineering modes of thinking

NASA Astrophysics Data System (ADS)

Patterson, Clair C.

1994-08-01

Powerful, latent abilities for extreme sophistication in abstract rationalization as potential biological adaptive behavioral responses were installed entirely through accident and inadvertence by biological evolution in the Homo sapiens sapiens species of brain. These potentials were never used, either in precursor species as factors in evolutionary increase in hominid brain mass, nor in less sophisticated forms within social environments characterized by Hss tribal brain population densities. Those latent abilities for unnatural biological adaptive behavior were forced to become manifest in various ways by growths in sophistication of communication interactions engendered by large growths in brain population densities brought on by developments in agriculture at the onset of the Holocene. It is proposed that differences probably exist between regions of the Hss brain involved in utilitarian, engineering types of problem conceptualization-solving versus regions of the brain involved in nonutilitarian, artistic-scientific types of problem conceptualization-solving. Populations isolated on separate continents from diffusive contact and influence on cultural developments, and selected for comparison of developments during equivalent stages of technological and social sophistication in matching 4000 year periods, show, at the ends of those periods, marked differences in aesthetic attributes expressed in cosmogonies, music, and writing (nonutilitarian thinking related to science and art). On the other hand the two cultures show virtually identical developments in three major stages of metallurgical technologies (utilitarian thinking related to engineering). Such archaeological data suggest that utilitarian modes of thought may utilize combinations of neuronal circuits in brain regions that are conserved among tribal populations territorially separated from each other for tens of thousands of years. Such conservation may not be true for neuronal circuits involved in nonutilitarian modes of thought. It is postulated that neuronal circuits involved in nonutilitarian modes of thought are located in specific regions of the brain that are divergent features between populations that have been territorially separated for tens of thousands of years. Anatomical PET and NMRI studies of brains of modern descendants of these cultures are proposed that would seek to define these inferred differences through proper protocols of stimulation devised by those investigators.

Familial and environmental influences on brain volumes in twins with schizophrenia.

PubMed

Picchioni, Marco M; Rijsdijk, Fruhling; Toulopoulou, Timothea; Chaddock, Christopher; Cole, James H; Ettinger, Ulrich; Oses, Ana; Metcalfe, Hugo; Murray, Robin M; McGuire, Philip

2017-03-01

Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear. We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually. We conducted between-group testing and full genetic modelling. We included 168 twins in our study. Whole brain, grey matter, white matter and right hippocampal volumes were smaller in twins with schizophrenia. Twin correlations were larger for whole brain, grey matter and white matter volumes in monozygotic than dizygotic twins and were significantly heritable, whereas hippocampal volume was the most environmentally sensitive. There was a significant phenotypic correlation between schizophrenia and reductions in all the brain volumes except for that of the left hippocampus. For whole brain, grey matter and the right hippocampus the etiological links with schizophrenia were principally associated with the shared familial environment. Lower birth weight and perinatal hypoxia were both associated with lower whole brain volume and with lower white matter and grey matter volumes, respectively. Scan data were collected across 2 sites, and some groups were modest in size. Whole brain, grey matter and right hippocampal volume reductions are linked to schizophrenia through correlated familial risk (i.e., the shared familial environment). The degree of influence of etiological factors varies between brain structures, leading to the possibility of a neuroanatomically specific etiological imprint.

Childhood adversity is linked to differential brain volumes in adolescents with alcohol use disorder: a voxel-based morphometry study.

PubMed

Brooks, Samantha J; Dalvie, Shareefa; Cuzen, Natalie L; Cardenas, Valerie; Fein, George; Stein, Dan J

2014-06-01

Previous neuroimaging studies link both alcohol use disorder (AUD) and early adversity to neurobiological differences in the adult brain. However, the association between AUD and childhood adversity and effects on the developing adolescent brain are less clear, due in part to the confound of psychiatric comorbidity. Here we examine early life adversity and its association with brain volume in a unique sample of 116 South African adolescents (aged 12-16) with AUD but without psychiatric comorbidity. Participants were 58 adolescents with DSM-IV alcohol dependence and with no other psychiatric comorbidities, and 58 age-, gender- and protocol-matched light/non-drinking controls (HC). Assessments included the Childhood Trauma Questionnaire (CTQ). MR images were acquired on a 3T Siemens Magnetom Allegra scanner. Volumes of global and regional structures were estimated using SPM8 Voxel Based Morphometry (VBM), with analysis of covariance (ANCOVA) and regression analyses. In whole brain ANCOVA analyses, a main effect of group when examining the AUD effect after covarying out CTQ was observed on brain volume in bilateral superior temporal gyrus. Subsequent regression analyses to examine how childhood trauma scores are linked to brain volumes in the total cohort revealed a negative correlation in the left hippocampus and right precentral gyrus. Furthermore, bilateral (but most significantly left) hippocampal volume was negatively associated with sub-scores on the CTQ in the total cohort. These findings support our view that some alterations found in brain volumes in studies of adolescent AUD may reflect the impact of confounding factors such as psychiatric comorbidity rather than the effects of alcohol per se. In particular, early life adversity may influence the developing adolescent brain in specific brain regions, such as the hippocampus.

Scientific meaning of meanings: quests for discoveries concerning our cultural ills.

PubMed

Patterson, C C

1998-08-01

This paper outlines pioneering concepts of fundamental physical and emotional features of the human brain which served as primary operators. These have developed during the past 10,000 years, giving rise to our present global megacultures and their various ancestral culture progenitors. Essential points are these: (1) Biological evolution endowed the human brain (quite inadvertently and unintentionally) with enormous latent powers for complex and sophisticated abstract ratiocinations. (2) Magnitudes of these latent powers grew exponentially with linear enlargements of brain size during the evolution of the genetic ancestors of Homo sapiens sapiens (Hss) during the past 3 million years, but these latent powers never materialized in utilized forms within the environmental contexts in which they evolved. (3) These sophisticated, abstract ratiocinations, both latent powers and operative forms in today's Hss brain, are divided between two major categories: utilitarian thinking and nonutilitarian thinking. (4) These two different types of thinking processes are carried out within separate, different regional combinations of neuronal biochemical entities within the same individual brain. (5) Sensitivities of abstract, sophisticated ratiocination processes within the human brain to influences from communication interactions with other human brains are exponentially greater in comparison with any other species of central nervous system in the earth's biosphere. This makes the brain population density the utmost critical factor, and determines the character of human thought within interacting populations of brains at a given time and place within a particular culture. (6) Abrupt increases of sedentary brain population densities, unnaturally greater by orders of magnitude than those that existed previously in biological evolutionary contexts, were engendered by the inauguration of agricultural practices 10,000 years ago. This enabled latent powers of the human brain used for complex and sophisticated abstract ratiocinations to become manifest in materialized forms of usage within relatively large groups of humans living i certain regions of the earth. (7) Thinking processes of the utilitarian category within brains living in such regions guided and dominated the development of sophisticated and complex social hierarchies and institutions, forms of communication, technologies, and cultures since that time. This dominating factor relegated thinking processes within the nonutilitarian categories of those brains to subservient roles during those developments. (8) Nonutilitarian abstracts ratiocinations possess a potential for proper adjudication and guidance of utilitarian abstract ratiocinations in the latter's development of culture. However, lack of the former's proper role in cultural developments since the beginning of the Holocene interglacial era has resulted in the imprisonment of Hss as aliens in an intellectual hell on a foreign planet.

Factors influencing frontal cortex development and recovery from early frontal injury.

PubMed

Halliwell, Celeste; Comeau, Wendy; Gibb, Robbin; Frost, Douglas O; Kolb, Bryan

2009-01-01

Neocortical development represents more than a simple unfolding of a genetic blueprint but rather represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Although most cortical regions are sensitive to a wide range of experiential factors during development and later in life, the prefrontal cortex appears to be unusually sensitive to perinatal experiences and relatively immune to many adulthood experiences relative to other neocortical regions. One way to examine experience-dependent prefrontal development is to conduct studies in which experiential perturbations are related neuronal morphology. This review of the research reveals both pre- and post-natal factors have important effects on prefrontal development and behaviour. Such factors include psychoactive drugs, including both illicit drugs and prescription drugs, stress, gonadal hormones and sensory and motor stimulation. A second method of study is to examine both the effects of perinatal prefrontal injury on the development of the remaining cerebral mantle and correlated behaviours as well as the effects of post-injury rehabilitation programmes on the anatomical and behavioural measures. Prefrontal injury alters cerebral development in a developmental-stage dependent manner with perinatal injuries having far more deleterious effects than similar injuries later in infancy. The outcome of perinatal injuries can be modified, however, by rehabilitation with many of the factors shown to influence prefrontal development in the otherwise normal brain.

Aerobic fitness relates to learning on a virtual Morris Water Task and hippocampal volume in adolescents.

PubMed

Herting, Megan M; Nagel, Bonnie J

2012-08-01

In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence--a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory. Published by Elsevier B.V.

Aerobic fitness relates to learning on a virtual morris water task and hippocampal volume in adolescents

PubMed Central

Herting, Megan M.; Nagel, Bonnie J.

2012-01-01

In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence – a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume, or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory. PMID:22610054

Mapping heritability and molecular genetic associations with cortical features using probabilistic brain atlases: methods and applications to schizophrenia.

PubMed

Cannon, Tyrone D; Thompson, Paul M; van Erp, Theo G M; Huttunen, Matti; Lonnqvist, Jouko; Kaprio, Jaakko; Toga, Arthur W

2006-01-01

There is an urgent need to decipher the complex nature of genotype-phenotype relationships within the multiple dimensions of brain structure and function that are compromised in neuropsychiatric syndromes such as schizophrenia. Doing so requires sophisticated methodologies to represent population variability in neural traits and to probe their heritable and molecular genetic bases. We have recently developed and applied computational algorithms to map the heritability of, as well as genetic linkage and association to, neural features encoded using brain imaging in the context of three-dimensional (3D), populationbased, statistical brain atlases. One set of algorithms builds on our prior work using classical twin study methods to estimate heritability by fitting biometrical models for additive genetic, unique, and common environmental influences. Another set of algorithms performs regression-based (Haseman-Elston) identical-bydescent linkage analysis and genetic association analysis of DNA polymorphisms in relation to neural traits of interest in the same 3D population-based brain atlas format. We demonstrate these approaches using samples of healthy monozygotic (MZ) and dizygotic (DZ) twin pairs, as well as MZ and DZ twin pairs discordant for schizophrenia, but the methods can be generalized to other classes of relatives and to other diseases. The results confirm prior evidence of genetic influences on gray matter density in frontal brain regions. They also provide converging evidence that the chromosome 1q42 region is relevant to schizophrenia by demonstrating linkage and association of markers of the Transelin-Associated-Factor-X and Disrupted-In- Schizophrenia-1 genes with prefrontal cortical gray matter deficits in twins discordant for schizophrenia.

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

PubMed Central

Landoni, Verónica I.; Schierloh, Pablo; de Campos Nebel, Marcelo; Fernández, Gabriela C.; Calatayud, Cecilia; Lapponi, María J.; Isturiz, Martín A.

2012-01-01

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS. PMID:22479186

Developmental effects of androgens in the human brain.

PubMed

Nguyen, T-V

2018-02-01

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions. © 2017 British Society for Neuroendocrinology.

Mind Reading and Writing: The Future of Neurotechnology.

PubMed

Roelfsema, Pieter R; Denys, Damiaan; Klink, P Christiaan

2018-05-02

Recent advances in neuroscience and technology have made it possible to record from large assemblies of neurons and to decode their activity to extract information. At the same time, available methods to stimulate the brain and influence ongoing processing are also rapidly expanding. These developments pave the way for advanced neurotechnological applications that directly read from, and write to, the human brain. While such technologies are still primarily used in restricted therapeutic contexts, this may change in the future once their performance has improved and they become more widely applicable. Here, we provide an overview of methods to interface with the brain, speculate about potential applications, and discuss important issues associated with a neurotechnologically assisted future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rehabilitation goal setting with community dwelling adults with acquired brain injury: a theoretical framework derived from clinicians' reflections on practice.

PubMed

Prescott, Sarah; Fleming, Jennifer; Doig, Emmah

2017-06-11

The aim of this study was to explore clinicians' experiences of implementing goal setting with community dwelling clients with acquired brain injury, to develop a goal setting practice framework. Grounded theory methodology was employed. Clinicians, representing six disciplines across seven services, were recruited and interviewed until theoretical saturation was achieved. A total of 22 clinicians were interviewed. A theoretical framework was developed to explain how clinicians support clients to actively engage in goal setting in routine practice. The framework incorporates three phases: a needs identification phase, a goal operationalisation phase, and an intervention phase. Contextual factors, including personal and environmental influences, also affect how clinicians and clients engage in this process. Clinicians use additional strategies to support clients with impaired self-awareness. These include structured communication and metacognitive strategies to operationalise goals. For clients with emotional distress, clinicians provide additional time and intervention directed at new identity development. The goal setting practice framework may guide clinician's understanding of how to engage in client-centred goal setting in brain injury rehabilitation. There is a predilection towards a client-centred goal setting approach in the community setting, however, contextual factors can inhibit implementation of this approach. Implications for Rehabilitation The theoretical framework describes processes used to develop achievable client-centred goals with people with brain injury. Building rapport is a core strategy to engage clients with brain injury in goal setting. Clients with self-awareness impairment benefit from additional metacognitive strategies to participate in goal setting. Clients with emotional distress may need additional time for new identity development.

Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study.

PubMed

Göbel, Anna; Heldmann, Marcus; Göttlich, Martin; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

2015-09-01

Hyper-as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.

White Matter Development in Adolescence: The Influence of Puberty and Implications for Affective Disorders

PubMed Central

Ladouceur, Cecile D.; Peper, Jiska S.; Crone, Eveline A.; Dahl, Ronald E.

2011-01-01

There have been rapid advances in understanding a broad range of changes in brain structure and function during adolescence, and a growing interest in identifying which of these neurodevelopmental changes are directly linked with pubertal maturation—at least in part because of their potential to provide insights into the numerous emotional and behavioral health problems that emerge during this developmental period. This review focuses on what is known about the influence of puberty on white matter development in adolescence. We focus on white matter because of its role in providing the structural architectural organization of the brain and as a structural correlate of communication within complex neural systems. We begin with a review of studies that report sex differences or sex by age interactions in white matter development as these findings can provide, although indirectly, information relevant to puberty-related changes. Studies are also critically reviewed based on methodological procedures used to assess pubertal maturation and relations with white matter changes. Findings are discussed in light of their implications for the development of neural systems underlying the regulation of emotion and behavior and how alterations in the development of these systems may mediate risk for affective disorders in vulnerable adolescents. PMID:22247751

Differential Brain Development with Low and High IQ in Attention-Deficit/Hyperactivity Disorder

PubMed Central

de Zeeuw, Patrick; Schnack, Hugo G.; van Belle, Janna; Weusten, Juliette; van Dijk, Sarai; Langen, Marieke; Brouwer, Rachel M.; van Engeland, Herman; Durston, Sarah

2012-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development. In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with below median IQ is associated more with a delay of cortical development. PMID:22536435

Biological Vulnerability to Alcoholism.

ERIC Educational Resources Information Center

Schuckit, Marc A.

1987-01-01

Reviews the role of biological factors in the risk for alcoholism. Notes the importance of the definition of primary alcoholism and highlights data indicating that this disorder is genetically influenced. In studies of men at high risk for the future development of alcoholism, vulnerability shows up in reactions to ethanol brain wave amplitude and…

Students' Study Abroad Plans: The Influence of Motivational and Personality Factors

ERIC Educational Resources Information Center

Li, Manyu; Olson, Josephine E.; Frieze, Irene Hanson

2013-01-01

Improving the international competencies of university students is becoming an important goal for both nations and universities. On the country level, national security and globalization trends are "driving nations to place more importance on developing and recruiting human capital or brain power through international education…

Elementary Teacher Perceptions Regarding the Use of Kinesthetic Learning Strategies

ERIC Educational Resources Information Center

Erickson, Heidi Christine

2017-01-01

Researchers have shown that movement increases brain function, improves mental health, supports cognitive development for students, and reduces sedentary time, all which can influence overall health. Research concerning learning with intentional movement is limited. In the United States, Common Core State Standards (CCSS) are being mandated, and…

Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

PubMed

Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

2015-07-01

Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (<1 mmol/L) and noncritical (>1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (P<0.05). For critical brain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus).

PubMed

Li, Minghui; Wang, Junsong; Lu, Zhaoguang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

2014-01-01

In this study, a (1)H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate-glutamine-gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment. Copyright © 2013 Elsevier B.V. All rights reserved.

Monte Carlo simulation of quantum Zeno effect in the brain

NASA Astrophysics Data System (ADS)

Georgiev, Danko

2015-12-01

Environmental decoherence appears to be the biggest obstacle for successful construction of quantum mind theories. Nevertheless, the quantum physicist Henry Stapp promoted the view that the mind could utilize quantum Zeno effect to influence brain dynamics and that the efficacy of such mental efforts would not be undermined by environmental decoherence of the brain. To address the physical plausibility of Stapp's claim, we modeled the brain using quantum tunneling of an electron in a multiple-well structure such as the voltage sensor in neuronal ion channels and performed Monte Carlo simulations of quantum Zeno effect exerted by the mind upon the brain in the presence or absence of environmental decoherence. The simulations unambiguously showed that the quantum Zeno effect breaks down for timescales greater than the brain decoherence time. To generalize the Monte Carlo simulation results for any n-level quantum system, we further analyzed the change of brain entropy due to the mind probing actions and proved a theorem according to which local projections cannot decrease the von Neumann entropy of the unconditional brain density matrix. The latter theorem establishes that Stapp's model is physically implausible but leaves a door open for future development of quantum mind theories provided the brain has a decoherence-free subspace.

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

Influence of strain rate on indentation response of porcine brain.

PubMed

Qian, Long; Zhao, Hongwei; Guo, Yue; Li, Yuanshang; Zhou, Mingxing; Yang, Liguo; Wang, Zhiwei; Sun, Yifan

2018-06-01

Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about some specific diseases mechanisms and its accurate simulations such as traumatic brain injury (TBI) and tumor growth. Compared to traditional tests (e.g. tensile and compression), indentation shows superiority by virtue of its pinpoint and nondestructive/quasi-nondestructive. As a viscoelastic material, the properties of brain tissue depend on the strain rate by definition. However most efforts focus on the aspect of velocity in the field of brain indentation, rather than strain rate. The influence of strain rate on indentation response of brain tissue is taken little attention. Further, by comparing different results from literatures, it is also obvious that strain rate rather than velocity is more appropriate to characterize mechanical properties of brain. In this paper, to systematically characterize the influence of strain rate, a series of indentation-relaxation tests n = 210) are performed on the cortex of porcine brain using a custom-designed indentation device. The mechanical response that correlates with indenter diameters, depths of indentation and velocities, is revealed for the indentation portion, and elastic behavior of brain tissue is analyzed as the function of strain rate. Similarly, a linear viscoelastic model with a Prony series is employed for the indentation-relaxation portion, wherein the brain tissue shows more viscous and responds more quickly with increasing strain rate. Understanding the effect of strain rate on mechanical properties of brain indentation may be far-reaching for brain injury biomechanics and accurate simulations, but be important for bridging between indentation results of different literatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular Imaging Provides Novel Insights on Estrogen Receptor Activity in Mouse Brain

PubMed Central

Stell, Alessia; Belcredito, Silvia; Ciana, Paolo; Maggi, Adriana

2009-01-01

Estrogen receptors have long been known to be expressed in several brain areas in addition to those directly involved in the control of reproductive functions. Investigations in humans and in animal models suggest a strong influence of estrogens on limbic and motor functions, yet the complexity and heterogeneity of neural tissue have limited our approaches to the full understanding of estrogen activity in the central nervous system. The aim of this study was to examine the transcriptional activity of estrogen receptors in the brain of male and female mice. Exploiting the ERE-Luc reporter mouse, we set up a novel, bioluminescence-based technique to study brain estrogen receptor transcriptional activity. Here we show, for the first time, that estrogen receptors are similarly active in male and female brains and that the estrous cycle affects estrogen receptor activity in regions of the central nervous system not known to be associated with reproductive functions. Because of its reproducibility and sensitivity, this novel bioluminescence application candidates as an innovative methodology for the study and development of drugs targeting brain estrogen receptors. PMID:19123998

Molecular imaging provides novel insights on estrogen receptor activity in mouse brain.

PubMed

Stell, Alessia; Belcredito, Silvia; Ciana, Paolo; Maggi, Adriana

2008-01-01

Estrogen receptors have long been known to be expressed in several brain areas in addition to those directly involved in the control of reproductive functions. Investigations in humans and in animal models suggest a strong influence of estrogens on limbic and motor functions, yet the complexity and heterogeneity of neural tissue have limited our approaches to the full understanding of estrogen activity in the central nervous system. The aim of this study was to examine the transcriptional activity of estrogen receptors in the brain of male and female mice. Exploiting the ERE-Luc reporter mouse, we set up a novel, bioluminescence-based technique to study brain estrogen receptor transcriptional activity. Here we show, for the first time, that estrogen receptors are similarly active in male and female brains and that the estrous cycle affects estrogen receptor activity in regions of the central nervous system not known to be associated with reproductive functions. Because of its reproducibility and sensitivity, this novel bioluminescence application stands as a candidate as an innovative methodology for the study and development of drugs targeting brain estrogen receptors.

Maternal anxiety and infants' hippocampal development: timing matters.

PubMed

Qiu, A; Rifkin-Graboi, A; Chen, H; Chong, Y-S; Kwek, K; Gluckman, P D; Fortier, M V; Meaney, M J

2013-09-24

Exposure to maternal anxiety predicts offspring brain development. However, because children's brains are commonly assessed years after birth, the timing of such maternal influences in humans is unclear. This study aimed to examine the consequences of antenatal and postnatal exposure to maternal anxiety upon early infant development of the hippocampus, a key structure for stress regulation. A total of 175 neonates underwent magnetic resonance imaging (MRI) at birth and among them 35 had repeated scans at 6 months of age. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI) at week 26 of pregnancy and 3 months after delivery. Regression analyses showed that antenatal maternal anxiety did not influence bilateral hippocampal volume at birth. However, children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life. This effect of antenatal maternal anxiety upon right hippocampal growth became statistically stronger when controlling for postnatal maternal anxiety. Furthermore, a strong positive association between postnatal maternal anxiety and right hippocampal growth was detected, whereas a strong negative association between postnatal maternal anxiety and the left hippocampal volume at 6 months of life was found. Hence, the postnatal growth of bilateral hippocampi shows distinct responses to postnatal maternal anxiety. The size of the left hippocampus during early development is likely to reflect the influence of the exposure to perinatal maternal anxiety, whereas right hippocampal growth is constrained by antenatal maternal anxiety, but enhanced in response to increased postnatal maternal anxiety.

Robust generative asymmetric GMM for brain MR image segmentation.

PubMed

Ji, Zexuan; Xia, Yong; Zheng, Yuhui

2017-11-01

Accurate segmentation of brain tissues from magnetic resonance (MR) images based on the unsupervised statistical models such as Gaussian mixture model (GMM) has been widely studied during last decades. However, most GMM based segmentation methods suffer from limited accuracy due to the influences of noise and intensity inhomogeneity in brain MR images. To further improve the accuracy for brain MR image segmentation, this paper presents a Robust Generative Asymmetric GMM (RGAGMM) for simultaneous brain MR image segmentation and intensity inhomogeneity correction. First, we develop an asymmetric distribution to fit the data shapes, and thus construct a spatial constrained asymmetric model. Then, we incorporate two pseudo-likelihood quantities and bias field estimation into the model's log-likelihood, aiming to exploit the neighboring priors of within-cluster and between-cluster and to alleviate the impact of intensity inhomogeneity, respectively. Finally, an expectation maximization algorithm is derived to iteratively maximize the approximation of the data log-likelihood function to overcome the intensity inhomogeneity in the image and segment the brain MR images simultaneously. To demonstrate the performances of the proposed algorithm, we first applied the proposed algorithm to a synthetic brain MR image to show the intermediate illustrations and the estimated distribution of the proposed algorithm. The next group of experiments is carried out in clinical 3T-weighted brain MR images which contain quite serious intensity inhomogeneity and noise. Then we quantitatively compare our algorithm to state-of-the-art segmentation approaches by using Dice coefficient (DC) on benchmark images obtained from IBSR and BrainWeb with different level of noise and intensity inhomogeneity. The comparison results on various brain MR images demonstrate the superior performances of the proposed algorithm in dealing with the noise and intensity inhomogeneity. In this paper, the RGAGMM algorithm is proposed which can simply and efficiently incorporate spatial constraints into an EM framework to simultaneously segment brain MR images and estimate the intensity inhomogeneity. The proposed algorithm is flexible to fit the data shapes, and can simultaneously overcome the influence of noise and intensity inhomogeneity, and hence is capable of improving over 5% segmentation accuracy comparing with several state-of-the-art algorithms. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC

PubMed Central

Swartling, Fredrik J.; Savov, Vasil; Persson, Anders I.; Chen, Justin; Hackett, Christopher S.; Northcott, Paul A.; Grimmer, Matthew R.; Lau, Jasmine; Chesler, Louis; Perry, Arie; Phillips, Joanna J.; Taylor, Michael D.; Weiss, William A.

2012-01-01

SUMMARY The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally-stabilized murine N-mycT58A into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem and forebrain. Transplantation of N-mycWT NSCs was insufficient for tumor formation. N-mycT58A cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating SHH-dependence and SHH-independence, respectively. These differences were regulated in-part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal. PMID:22624711

Metabolic adaptation to long term changes in gravity environment

NASA Astrophysics Data System (ADS)

Slenzka, K.; Appel, R.; Rahmann, H.

Biochemical analyses of the brain of Cichlid fish larvae, exposed during their very early development for 7 days to an increased acceleration of 3g (hyper-gravity), revealed a decrease in brain nucleoside diphosphate kinase (NDPK) as well as creatine kinase (BB-CK) activity. Using high performance liquid chromatography (HPLC) the concentrations of adenine nucleotides (AMP, ADP, ATP), phosphocreatine (CP), as well as of nicotineamide adenine dinucleotides (NAD, NADP) were analyzed in the brain of hyper-g exposed larvae vs. 1g controls. A slight reduction in the total adenine nucleotides (TAN) as well as the adenylate energy charge (AEC) was found. In parallel a significant increase in the NAD concentration and a corresponding decrease in NADP concentration occurred in larva's hyper-g brains vs. 1g controls. These results give further evidence for an influence of gravity on cellular level and furthermore contribute to a clarification of the cellular signal-response chain for gravity perception.

[Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].

PubMed

Konturek, Peter C; Zopf, Yurdagül

2016-05-25

The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. Overview Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.

Wired on steroids: sexual differentiation of the brain and its role in the expression of sexual partner preferences.

PubMed

Alexander, Brenda M; Skinner, Donal C; Roselli, Charles E

2011-01-01

The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rat, ferret, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods result in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity.

Wired on Steroids: Sexual Differentiation of the Brain and Its Role in the Expression of Sexual Partner Preferences

PubMed Central

Alexander, Brenda M.; Skinner, Donal C.; Roselli, Charles E.

2011-01-01

The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rat, ferret, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods result in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity. PMID:22654808

Pilot study of brain morphometry in a sample of Brazilian children with attention deficit hyperactivity disorder: influence of clinical presentation.

PubMed

Pastura, Giuseppe; Kubo, Tadeu Takao Almodovar; Gasparetto, Emerson Leandro; Figueiredo, Otavio; Mattos, Paulo; Prüfer Araújo, Alexandra

2017-12-01

Currently, the diagnosis of attention deficit hyperactivity disorder (ADHD) rests on clinical criteria. Nonetheless, neuroimaging studies have demonstrated that children with ADHD have different cortical thickness and volume measures to typically developing children (TDC). In general, studies do not evaluate the influence of clinical presentation in the brain morphometry of ADHD children. Our objective was to perform a pilot study in order to evaluate cortical thickness and brain volume in a sample of Brazilian ADHD children and compare these to those of TDC, taking into account the influence of clinical presentation. We performed an analytic study comparing 17 drug-naïve ADHD children of both genders, aged between 7 and 10, and 16 TDC. ADHD subjects were first considered as one group and further separated based on clinical presentation. The brain volume did not differ between patients and TDC. Smaller cortical thicknesses were identified on the left superior, medium and inferior temporal cortex, as well as in the left inferior parietal cortex. When compared to TDC, combined and inattentive ADHD presentations depicted smaller cortical thickness with high significance and power. The same magnitude of results was not observed when comparing inattentive ADHD and TDC. In this pilot study, ADHD is associated with abnormalities involving the cortical thickness of the posterior attentional system. The cortical thickness in the left superior, medium and inferior temporal cortex, as well as in the left inferior parietal cortex may differ according to ADHD presentations.

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

PubMed Central

Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P.

2016-01-01

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

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.

Nicotine and the adolescent brain

PubMed Central

Yuan, Menglu; Cross, Sarah J; Loughlin, Sandra E; Leslie, Frances M

2015-01-01

Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse. PMID:26018031

Attachment Security in Infancy: A Preliminary Study of Prospective Links to Brain Morphometry in Late Childhood

PubMed Central

Leblanc, Élizabel; Dégeilh, Fanny; Daneault, Véronique; Beauchamp, Miriam H.; Bernier, Annie

2017-01-01

A large body of longitudinal research provides compelling evidence for the critical role of early attachment relationships in children’s social, emotional, and cognitive development. It is expected that parent–child attachment relationships may also impact children’s brain development, however, studies linking normative caregiving experiences and brain structure are scarce. To our knowledge, no study has yet examined the associations between the quality of parent–infant attachment relationships and brain morphology during childhood. The aim of this preliminary study was to investigate the prospective links between mother–infant attachment security and whole-brain gray matter (GM) volume and thickness in late childhood. Attachment security toward the mother was assessed in 33 children when they were 15 months old. These children were then invited to undergo structural magnetic resonance imaging at 10–11 years of age. Results indicated that children more securely attached to their mother in infancy had larger GM volumes in the superior temporal sulcus and gyrus, temporo-parietal junction, and precentral gyrus in late childhood. No associations between attachment security and cortical thickness were found. If replicated, these results would suggest that a secure attachment relationship and its main features (e.g., adequate dyadic emotion regulation, competent exploration) may influence GM volume in brain regions involved in social, cognitive, and emotional functioning through experience-dependent processes. PMID:29312029

Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children

PubMed Central

El Marroun, Hanan; Schmidt, Marcus N; Franken, Ingmar H A; Jaddoe, Vincent W V; Hofman, Albert; van der Lugt, Aad; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

2014-01-01

It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6–8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children. PMID:24096296

Mind the movement: Frontal asymmetry stands for behavioral motivation, bilateral frontal activation for behavior.

PubMed

Rodrigues, Johannes; Müller, Mathias; Mühlberger, Andreas; Hewig, Johannes

2018-01-01

Frontal asymmetry has been investigated over the past 30 years, and several theories have been developed about its meaning. The original theory of Davidson and its diversification by Harmon-Jones & Allen allocated approach motivation to relative left frontal brain activity and withdrawal motivation to relative right frontal brain activity. Hewig and colleagues extended this theory by adding bilateral frontal activation representing a biological correlate of the behavioral activation system if actual behavior is shown. Wacker and colleagues formulated a theory related to the revised reinforcement sensitivity theory by Gray & McNaughton. Here, relative left frontal brain activation represents the revised behavioral activation system and behavior, while relative right frontal brain activation represents the revised behavioral inhibition system, representing the experience of conflict. These theories were investigated with a newly developed paradigm where participants were able to move around freely in a virtual T maze via joystick while having their EEG recorded. Analyzing the influence of frontal brain activation during this virtual reality task on observable behavior for 30 participants, we found more relative left frontal brain activation during approach behavior and more relative right brain activation for withdrawal behavior of any kind. Additionally, there was more bilateral frontal brain activation when participants were engaged in behavior compared to doing nothing. Hence, this study provides evidence for the idea that frontal asymmetry stands for behavioral approach or avoidance motivation, and bilateral frontal activation stands for behavior. Additionally, observable behavior is not only determined by frontal asymmetry, but also by relevant traits. © 2017 Society for Psychophysiological Research.

Brain foods: the effects of nutrients on brain function

PubMed Central

Gómez-Pinilla, Fernando

2009-01-01

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness. PMID:18568016

Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.

PubMed

van Vliet, Danique; Bruinenberg, Vibeke M; Mazzola, Priscila N; van Faassen, Martijn Hjr; de Blaauw, Pim; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Kema, Ido P; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; van Spronsen, Francjan J

2016-11-01

Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high-protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus provides essential information for the development of optimal LNAA supplementation as an alternative dietary treatment strategy to optimize neurocognitive outcome in patients with phenylketonuria. © 2016 American Society for Nutrition.

Effects of exogenous agents on brain development: stress, abuse and therapeutic compounds.

PubMed

Archer, Trevor

2011-10-01

The range of exogenous agents likely to affect, generally detrimentally, the normal development of the brain and central nervous system defies estimation although the amount of accumulated evidence is enormous. The present review is limited to certain types of chemotherapeutic and "use-and-abuse" compounds and environmental agents, exemplified by anesthetic, antiepileptic, sleep-inducing and anxiolytic compounds, nicotine and alcohol, and stress as well as agents of infection; each of these agents have been investigated quite extensively and have been shown to contribute to the etiopathogenesis of serious neuropsychiatric disorders. To greater or lesser extent, all of the exogenous agents discussed in the present treatise have been investigated for their influence upon neurodevelopmental processes during the period of the brain growth spurt and during other phases uptill adulthood, thereby maintaining the notion of critical phases for the outcome of treatment whether prenatal, postnatal, or adolescent. Several of these agents have contributed to the developmental disruptions underlying structural and functional brain abnormalities that are observed in the symptom and biomarker profiles of the schizophrenia spectrum disorders and the fetal alcohol spectrum disorders. In each case, the effects of the exogenous agents upon the status of the affected brain, within defined parameters and conditions, is generally permanent and irreversible. © 2010 Blackwell Publishing Ltd.

Neural Correlates of Social Influence on Risk Taking and Substance Use in Adolescents.

PubMed

Telzer, Eva H; Rogers, Christina R; Van Hoorn, Jorien

2017-09-01

Adolescents often engage in elevated levels of risk taking that gives rise to substance use. Family and peers constitute the primary contextual risk factors for adolescent substance use. This report reviews how families and peers influence adolescent neurocognitive development to inform their risk taking and subsequent substance use. Developmental neuroscience using functional magnetic resonance imaging (fMRI) has identified regions of the brain involved in social cognition, cognitive control, and reward processing that are integrally linked to social influence on adolescent risk taking. These neural mechanisms play a role in how peer and family influence (e.g., physical presence, relationship quality, rejection) translates into adolescent substance use. Peers and families can independently, and in tandem, contribute to adolescent substance use, for better or for worse. We propose that future work utilize fMRI to investigate the neural mechanisms involved in different aspects of peer and family influence, and how these contexts uniquely and interactively influence adolescent substance use initiation and escalation across development.

The Infant Microbiome: Implications for Infant Health and Neurocognitive Development

PubMed Central

Yang, Irene; Corwin, Elizabeth J.; Brennan, Patricia A.; Jordan, Sheila; Murphy, Jordan R.; Dunlop, Anne

2015-01-01

Background Beginning at birth, the microbes in the gut perform essential duties related to the digestion and metabolism of food, the development and activation of the immune system, and the production of neurotransmitters that affect behavior and cognitive function. Objectives The objectives of this review are to: (a) provide a brief overview of the microbiome and the “microbiome-gut-brain axis”; (b) discuss factors known to affect the composition of the infant microbiome: mode of delivery, antibiotic exposure, and infant feeding patterns; and (c) present research priorities for nursing science, and clinical implications for infant health and neurocognitive development. Discussion The gut microbiome influences immunological, endocrine, and neural pathways and plays an important role in infant development. Several factors influence colonization of the infant gut microbiome. Different microbial colonization patterns are associated with vaginal versus surgical birth, exposure to antibiotics, and infant feeding patterns. Because of extensive physiological influence, infant microbial colonization patterns have the potential to impact physical and neurocognitive development and life course disease risk. Understanding these influences will inform newborn care and parental education. PMID:26657483

Basic emotion processing and the adolescent brain: Task demands, analytic approaches, and trajectories of changes.

PubMed

Del Piero, Larissa B; Saxbe, Darby E; Margolin, Gayla

2016-06-01

Early neuroimaging studies suggested that adolescents show initial development in brain regions linked with emotional reactivity, but slower development in brain structures linked with emotion regulation. However, the increased sophistication of adolescent brain research has made this picture more complex. This review examines functional neuroimaging studies that test for differences in basic emotion processing (reactivity and regulation) between adolescents and either children or adults. We delineated different emotional processing demands across the experimental paradigms in the reviewed studies to synthesize the diverse results. The methods for assessing change (i.e., analytical approach) and cohort characteristics (e.g., age range) were also explored as potential factors influencing study results. Few unifying dimensions were found to successfully distill the results of the reviewed studies. However, this review highlights the potential impact of subtle methodological and analytic differences between studies, need for standardized and theory-driven experimental paradigms, and necessity of analytic approaches that are can adequately test the trajectories of developmental change that have recently been proposed. Recommendations for future research highlight connectivity analyses and non-linear developmental trajectories, which appear to be promising approaches for measuring change across adolescence. Recommendations are made for evaluating gender and biological markers of development beyond chronological age. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thyroid hormones: Possible roles in epilepsy pathology.

PubMed

Tamijani, Seyedeh Masoumeh Seyedhoseini; Karimi, Benyamin; Amini, Elham; Golpich, Mojtaba; Dargahi, Leila; Ali, Raymond Azman; Ibrahim, Norlinah Mohamed; Mohamed, Zahurin; Ghasemi, Rasoul; Ahmadiani, Abolhassan

2015-09-01

Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Music From the Very Beginning-A Neuroscience-Based Framework for Music as Therapy for Preterm Infants and Their Parents.

PubMed

Haslbeck, Friederike Barbara; Bassler, Dirk

2018-01-01

Human and animal studies demonstrate that early auditory experiences influence brain development. The findings are particularly crucial following preterm birth as the plasticity of auditory regions, and cortex development are heavily dependent on the quality of auditory stimulation. Brain maturation in preterm infants may be affected among other things by the overwhelming auditory environment of the neonatal intensive care unit (NICU). Conversely, auditory deprivation, (e.g., the lack of the regular intrauterine rhythms of the maternal heartbeat and the maternal voice) may also have an impact on brain maturation. Therefore, a nurturing enrichment of the auditory environment for preterm infants is warranted. Creative music therapy (CMT) addresses these demands by offering infant-directed singing in lullaby-style that is continually adapted to the neonate's needs. The therapeutic approach is tailored to the individual developmental stage, entrained to the breathing rhythm, and adapted to the subtle expressions of the newborn. Not only the therapist and the neonate but also the parents play a role in CMT. In this article, we describe how to apply music therapy in a neonatal intensive care environment to support very preterm infants and their families. We speculate that the enriched musical experience may promote brain development and we critically discuss the available evidence in support of our assumption.

Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior

PubMed Central

Notarangelo, Francesca M.; Pocivavsek, Ana

2016-01-01

The kynurenine pathway (KP) of tryptophan degradation contains several neuroactive metabolites that may influence brain function in health and disease. Mounting focus has been dedicated to investigating the role of these metabolites during neurodevelopment and elucidating their involvement in the pathophysiology of psychiatric disorders with a developmental component, such as schizophrenia. In this review, we describe the changes in KP metabolism in the brain from gestation until adulthood and illustrate how environmental and genetic factors affect the KP during development. With a particular focus on kynurenic acid, the antagonist of α7 nicotinic acetylcholine (α7nACh) and N-methyl-D-aspartate (NMDA) receptors, both implicated in modulating brain development, we review animal models designed to ascertain the role of perinatal KP elevation on long-lasting biochemical, neuropathological, and behavioral deficits later in life. We present new data demonstrating that combining perinatal choline-supplementation, to potentially increase activation of α7nACh receptors during development, with embryonic kynurenine manipulation is effective in attenuating cognitive impairments in adult rat offspring. With these findings in mind, we conclude the review by discussing the advancement of therapeutic interventions that would target not only symptoms, but potentially the root cause of central nervous system diseases that manifest from a perinatal KP insult. PMID:26944732

Basic emotion processing and the adolescent brain: Task demands, analytic approaches, and trajectories of changes

PubMed Central

Del Piero, Larissa B.; Saxbe, Darby E.; Margolin, Gayla

2016-01-01

Early neuroimaging studies suggested that adolescents show initial development in brain regions linked with emotional reactivity, but slower development in brain structures linked with emotion regulation. However, the increased sophistication of adolescent brain research has made this picture more complex. This review examines functional neuroimaging studies that test for differences in basic emotion processing (reactivity and regulation) between adolescents and either children or adults. We delineated different emotional processing demands across the experimental paradigms in the reviewed studies to synthesize the diverse results. The methods for assessing change (i.e., analytical approach) and cohort characteristics (e.g., age range) were also explored as potential factors influencing study results. Few unifying dimensions were found to successfully distill the results of the reviewed studies. However, this review highlights the potential impact of subtle methodological and analytic differences between studies, need for standardized and theory-driven experimental paradigms, and necessity of analytic approaches that are can adequately test the trajectories of developmental change that have recently been proposed. Recommendations for future research highlight connectivity analyses and nonlinear developmental trajectories, which appear to be promising approaches for measuring change across adolescence. Recommendations are made for evaluating gender and biological markers of development beyond chronological age. PMID:27038840

Disentangling How the Brain is "Wired" in Cortical (Cerebral) Visual Impairment.

PubMed

Merabet, Lotfi B; Mayer, D Luisa; Bauer, Corinna M; Wright, Darick; Kran, Barry S

2017-05-01

Cortical (cerebral) visual impairment (CVI) results from perinatal injury to visual processing structures and pathways of the brain and is the most common cause of severe visual impairment or blindness in children in developed countries. Children with CVI display a wide range of visual deficits including decreased visual acuity, impaired visual field function, as well as impairments in higher-order visual processing and attention. Together, these visual impairments can dramatically influence a child's development and well-being. Given the complex neurologic underpinnings of this condition, CVI is often undiagnosed by eye care practitioners. Furthermore, the neurophysiological basis of CVI in relation to observed visual processing deficits remains poorly understood. Here, we present some of the challenges associated with the clinical assessment and management of individuals with CVI. We discuss how advances in brain imaging are likely to help uncover the underlying neurophysiology of this condition. In particular, we demonstrate how structural and functional neuroimaging approaches can help gain insight into abnormalities of white matter connectivity and cortical activation patterns, respectively. Establishing a connection between how changes within the brain relate to visual impairments in CVI will be important for developing effective rehabilitative and education strategies for individuals living with this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications

PubMed Central

Felger, Jennifer C.; Lotrich, Francis E.

2013-01-01

Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, e.g. brain derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression’s development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. PMID:23644052

Importance of partitioning membranes of the brain and the influence of the neck in head injury modelling.

PubMed

Kumaresan, S; Radhakrishnan, S

1996-01-01

A head injury model consisting of the skull, the CSF, the brain and its partitioning membranes and the neck region is simulated by considering its near actual geometry. Three-dimensional finite-element analysis is carried out to investigate the influence of the partitioning membranes of the brain and the neck in head injury analysis through free-vibration analysis and transient analysis. In free-vibration analysis, the first five modal frequencies are calculated, and in transient analysis intracranial pressure and maximum shear stress in the brain are determined for a given occipital impact load.

Perinatal treatment of rats with opiates affects the development of the blood-brain barrier transport system PTS-1.

PubMed

Banks, W A; Kastin, A J; Harrison, L M; Zadina, J E

1996-01-01

Previous results have shown that treatment of rats with morphine during the neonatal period can influence development of peptide transport system-1 (PTS-1), the blood-brain barrier transport system for Tyr-MIF-1 and methionine enkephalin. Previous work has suggested that the activity level of PTS-1 correlates with the concentration of methionine enkephalin in the brain. We show here that rats treated peripherally with morphine sulfate (MS) in both the prenatal and neonatal periods have enhanced activity of PTS-1. The degree of enhancement increases with age to reach a 66% increase in comparison with controls at age 9 weeks. The mu agonist MS was more powerful than the kappa agonist ethylketocyclazocine (EKC) or the delta agonist [D-Pen2.5,pCl-Phe4]enkephalin (pCl-DPDPE) in producing this effect. Opiate antagonists had complex effects with methylnaltrexone blocking the action of MS on PTS-1. These results show that the level of PTS-1 activity in adult rats can be modified by perinatal events that affect opiate tone during development.

Influences of brain tissue poroelastic constants on intracranial pressure (ICP) during constant-rate infusion.

PubMed

Li, Xiaogai; von Holst, Hans; Kleiven, Svein

2013-01-01

A 3D finite element (FE) model has been developed to study the mean intracranial pressure (ICP) response during constant-rate infusion using linear poroelasticity. Due to the uncertainties in the poroelastic constants for brain tissue, the influence of each of the main parameters on the transient ICP infusion curve was studied. As a prerequisite for transient analysis, steady-state simulations were performed first. The simulated steady-state pressure distribution in the brain tissue for a normal cerebrospinal fluid (CSF) circulation system showed good correlation with experiments from the literature. Furthermore, steady-state ICP closely followed the infusion experiments at different infusion rates. The verified steady-state models then served as a baseline for the subsequent transient models. For transient analysis, the simulated ICP shows a similar tendency to that found in the experiments, however, different values of the poroelastic constants have a significant effect on the infusion curve. The influence of the main poroelastic parameters including the Biot coefficient α, Skempton coefficient B, drained Young's modulus E, Poisson's ratio ν, permeability κ, CSF absorption conductance C(b) and external venous pressure p(b) was studied to investigate the influence on the pressure response. It was found that the value of the specific storage term S(ε) is the dominant factor that influences the infusion curve, and the drained Young's modulus E was identified as the dominant parameter second to S(ε). Based on the simulated infusion curves from the FE model, artificial neural network (ANN) was used to find an optimised parameter set that best fit the experimental curve. The infusion curves from both the FE simulation and using ANN confirmed the limitation of linear poroelasticity in modelling the transient constant-rate infusion.

Epigenetics and Psychoneuroimmunology: Mechanisms and Models

PubMed Central

Mathews, Herbert L.; Janusek, Linda Witek

2010-01-01

In this Introduction to the Named Series “Epigenetics, Brain, Behavior, and Immunity” an overview of epigenetics is provided with a consideration of the nature of epigenetic regulation including DNA methylation, histone modification and chromatin remodeling. Illustrative examples of recent scientific developments are highlighted to demonstrate the influence of epigenetics in areas of research relevant to those who investigate phenomena within the scientific discipline of psychoneuroimmunology. These examples are presented in order to provide a perspective on how epigenetic analysis will add insight into the molecular processes that connect the brain with behavior, neuroendocrine responsivity and immune outcome. PMID:20832468

Neuroethics vs neurophysiologically and neuropsychologically uninformed influences in child-rearing, education, emerging hunter-gatherers, and artificial intelligence models of the brain.

PubMed

Pontius, A A

1993-04-01

Potentially negative long-term consequences in four areas are emphasized, if specific neuromaturational, neurophysiological, and neuropsychological facts within a neurodevelopmental and ecological context are neglected in normal functional levels of child development and maturational lag of the frontal lobe system in "Attention Deficit Disorder," in education (reading/writing and arithmetic), in assessment of cognitive functioning in hunter-gatherer populations, specifically modified in the service of their survival, and in constructing computer models of the brain, neglecting consciousness and intentionality as criticized recently by Searle.

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.

PubMed

Preciados, Mark; Yoo, Changwon; Roy, Deodutta

2016-12-13

During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of these genes are involved with brain diseases, such as Alzheimer's Disease (AD), Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD- APOE , APP , ATP5A1 , CALM1 , CASP3 , GSK3B , IL1B , MAPT , PSEN2 and TNF- underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2 , DPYSL2 , EIF2S1 , ENO1 , MAPT , and PAXIP1 . These genes are also responsive to the following EEDs: ethinyl estradiol ( APBB2 , DPYSL2 , EIF2S1 , ENO1 , MAPT , and PAXIP1 ), BPA ( APBB2 , EIF2S1 , ENO1 , MAPT , and PAXIP1 ), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate ( DPYSL2 and MAPT ). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely different from male human AD patients. AD-associated NRF1 target genes- APLP1 , APP , GRIN1 , GRIN2B , MAPT , PSEN2 , PEN2 , and IDE -are also regulated by E2. NRF1 regulates targets genes with diverse functions, including cell growth, apoptosis/autophagy, mitochondrial biogenesis, genomic instability, neurogenesis, neuroplasticity, synaptogenesis, and senescence. By activating or repressing the genes involved in cell proliferation, growth suppression, DNA damage/repair, apoptosis/autophagy, angiogenesis, estrogen signaling, neurogenesis, synaptogenesis, and senescence, and inducing a wide range of DNA damage, genomic instability and DNA methylation and transcriptional repression, NRF1 may act as a major regulator of EEDs-induced brain health deficits. In summary, estrogenic endocrine disrupting chemicals-modified genes in brain health deficits are part of both estrogen and NRF1 signaling pathways. Our findings suggest that in addition to estrogen signaling, EEDs influencing NRF1 regulated communities of genes across genomic and epigenomic multiple networks may contribute in the development of complex chronic human brain health disorders.

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

PubMed Central

Wood, JodiAnne T.; Williams, John S.; Pandarinathan, Lakshmipathi; Janero, David R.; Lammi-Keefe, Carol J.; Makriyannis, Alexandros

2010-01-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications. PMID:20071693

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma.

PubMed

Wood, Jodianne T; Williams, John S; Pandarinathan, Lakshmipathi; Janero, David R; Lammi-Keefe, Carol J; Makriyannis, Alexandros

2010-06-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications.

IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

PubMed Central

Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

2012-01-01

The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

Art and the brain: the influence of frontotemporal dementia on an accomplished artist.

PubMed

Mell, Joshua Chang; Howard, Sara M; Miller, Bruce L

2003-05-27

A talented artist developed a progressive aphasia syndrome associated with frontotemporal dementia (FTD). As her disease progressed, language and executive skills declined, but her paintings became freer and more original. She demonstrates that artistic development can occur in the setting of language-dominant types of FTD. The study of artistic development in the setting of FTD suggests that language is not required for, and may even inhibit, certain types of visual creativity.

Infant Hand Preference and the Development of Cognitive Abilities

PubMed Central

Michel, George F.; Campbell, Julie M.; Marcinowski, Emily C.; Nelson, Eliza L.; Babik, Iryna

2016-01-01

Hand preference develops in the first two postnatal years with nearly half of infants exhibiting a consistent early preference for acquiring objects. Others exhibit a more variable developmental trajectory but by the end of their second postnatal year, most exhibit a consistent hand preference for role-differentiated bimanual manipulation. According to some forms of embodiment theory, these differences in hand use patterns should influence the way children interact with their environments, which, in turn, should affect the structure and function of brain development. Such early differences in brain development should result in different trajectories of psychological development. We present evidence that children with consistent early hand preferences exhibit advanced patterns of cognitive development as compared to children who develop a hand preference later. Differences in the developmental trajectory of hand preference are predictive of developmental differences in language, object management skills, and tool-use skills. As predicted by Casasanto’s body-specificity hypothesis, infants with different hand preferences proceed along different developmental pathways of cognitive functioning. PMID:27047431

Pointwise influence matrices for functional-response regression.

PubMed

Reiss, Philip T; Huang, Lei; Wu, Pei-Shien; Chen, Huaihou; Colcombe, Stan

2017-12-01

We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise influence matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers in an analysis of the development of white matter microstructure in the brain. © 2017, The International Biometric Society.

Comparison of two freely available software packages for mass spectrometry imaging data analysis using brains from morphine addicted rats.

PubMed

Bodzon-Kulakowska, Anna; Marszalek-Grabska, Marta; Antolak, Anna; Drabik, Anna; Kotlinska, Jolanta H; Suder, Piotr

Data analysis from mass spectrometry imaging (MSI) imaging experiments is a very complex task. Most of the software packages devoted to this purpose are designed by the mass spectrometer manufacturers and, thus, are not freely available. Laboratories developing their own MS-imaging sources usually do not have access to the commercial software, and they must rely on the freely available programs. The most recognized ones are BioMap, developed by Novartis under Interactive Data Language (IDL), and Datacube, developed by the Dutch Foundation for Fundamental Research of Matter (FOM-Amolf). These two systems were used here for the analysis of images received from rat brain tissues subjected to morphine influence and their capabilities were compared in terms of ease of use and the quality of obtained results.

Infant Frontal Asymmetry Predicts Child Emotional Availability

ERIC Educational Resources Information Center

Licata, Maria; Paulus, Markus; Kühn-Popp, Nina; Meinhardt, Jorg; Sodian, Beate

2015-01-01

While factors influencing maternal emotional availability (EA) have been well investigated, little is known about the development of child EA. The present longitudinal study investigated the role of frontal brain asymmetry in young children with regard to child EA (child responsiveness and involvement) in mother-child interaction in a sample of 28…

Early Childhood Household Smoke Exposure Predicts Less Task-Oriented Classroom Behavior at Age 10

ERIC Educational Resources Information Center

Pagani, Linda S.; Fitzpatrick, Caroline

2016-01-01

Secondhand tobacco smoke is considered a developmental neurotoxicant especially given underdeveloped vital systems in young children. An ecological test of its negative influence on brain development can be made by examining the prospective association between early childhood household smoke exposure and later classroom behavior. Using a…

The "Hard Problem" and the Quantum Physicists. Part 1: The First Generation

ERIC Educational Resources Information Center

Smith, C. U. M.

2006-01-01

All four of the most important figures in the early twentieth-century development of quantum physics--Niels Bohr, Erwin Schroedinger, Werner Heisenberg and Wolfgang Pauli--had strong interests in the traditional mind--brain, or "hard," problem. This paper reviews their approach to this problem, showing the influence of Bohr's complementarity…

Neuromaturation and Adolescent Risk Taking: Why Development Is Not Determinism

ERIC Educational Resources Information Center

Johnson, Sara B.; Sudhinaraset, May; Blum, Robert Wm.

2010-01-01

In the January 2009 issue of this journal, Males argues that adolescent brain science perpetuates the "myth of adolescent risk taking." He contends that those who study adolescent neuromaturation are biological determinists who ignore the profound social and environmental forces that influence adolescent behavior to further their own agendas.…

Infants and Toddlers, 2000-2001.

ERIC Educational Resources Information Center

Kroenke, Lillian DeVault, Ed.

2000-01-01

This document is comprised of the four 2000-2001 issues of a quarterly journal for teachers and parents of children in Montessori infant and toddler programs. The Spring 2000 issue presents articles on introducing cultural subjects to toddlers and on the influence of early experience on brain development. The Summer 2000 issue includes an article…

The importance of puberty for adolescent development: conceptualization and measurement.

PubMed

Berenbaum, Sheri A; Beltz, Adriene M; Corley, Robin

2015-01-01

How and why are teenagers different from children and adults? A key question concerns the ways in which pubertal development shapes psychological changes in adolescence directly through changes to the brain and indirectly through the social environment. Empirical work linking pubertal development to adolescent psychological function draws from several different perspectives, often with varying approaches and a focus on different outcomes and mechanisms. The main themes concern effects of atypical pubertal timing on behavior problems during adolescence, effects of pubertal status (and associated hormones) on normative changes in behaviors that can facilitate or hinder development (especially risk-taking, social reorientation, and stress responsivity), and the role of puberty in triggering psychopathology in vulnerable individuals. There is also interest in understanding the ways in which changes in the brain reflect pubertal processes and underlie psychological development in adolescence. In this chapter, we consider the ways that puberty might affect adolescent psychological development, and why this is of importance to developmentalists. We describe the processes of pubertal development; summarize what is known about pubertal influences on adolescent development; consider the assumptions that underlie most work and the methodological issues that affect the interpretation of results; and propose research directions to help understand paths from puberty to behavior. Throughout, we emphasize the importance of pubertal change in all aspects of psychological development, and the ways in which puberty represents an opportunity to study the interplay of biological and social influences. © 2015 Elsevier Inc. All rights reserved.

Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

PubMed

Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L

2015-09-01

The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.

Early life stress is associated with default system integrity and emotionality during infancy.

PubMed

Graham, Alice M; Pfeifer, Jennifer H; Fisher, Philip A; Carpenter, Samuel; Fair, Damien A

2015-11-01

Extensive animal research has demonstrated the vulnerability of the brain to early life stress (ELS) with consequences for emotional development and mental health. However, the influence of moderate and common forms of stress on early human brain development is less well-understood and precisely characterized. To date, most work has focused on severe forms of stress, and/or on brain functioning years after stress exposure. In this report we focused on conflict between parents (interparental conflict), a common and relatively moderate form of ELS that is highly relevant for children's mental health outcomes. We used resting state functional connectivity MRI to examine the coordinated functioning of the infant brain (N = 23; 6-12-months-of-age) in the context of interparental conflict. We focused on the default mode network (DMN) due to its well-characterized developmental trajectory and implications for mental health. We further examined DMN strength as a mediator between conflict and infants' negative emotionality. Higher interparental conflict since birth was associated with infants showing stronger connectivity between two core DMN regions, the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC). PCC to amygdala connectivity was also increased. Stronger PCC-aMPFC connectivity mediated between higher conflict and higher negative infant emotionality. The developing DMN may be an important marker for effects of ELS with relevance for emotional development and subsequent mental health. Increasing understanding of the associations between common forms of family stress and emerging functional brain networks has potential to inform intervention efforts to improve mental health outcomes. © 2015 Association for Child and Adolescent Mental Health.

Early life stress is associated with default system integrity and emotionality during infancy

PubMed Central

Graham, Alice M.; Pfeifer, Jennifer H.; Fisher, Philip A.; Carpenter, Samuel; Fair, Damien A.

2015-01-01

Background Extensive animal research has demonstrated the vulnerability of the brain to early life stress (ELS) with consequences for emotional development and mental health. However, the influence of moderate and common forms of stress on early human brain development is less well understood and precisely characterized. To date, most work has focused on severe forms of stress, and/or on brain functioning years after stress exposure. Methods In this report we focused on conflict between parents (interparental conflict), a common and relatively moderate form of ELS that is highly relevant for children's mental health outcomes. We used resting state functional connectivity MRI to examine the coordinated functioning of the infant brain (N=23; 6–12-months-of-age) in the context of interparental conflict. We focused on the default mode network (DMN) due to its well characterized developmental trajectory and implications for mental health. We further examined DMN strength as a mediator between conflict and infants’ negative emotionality. Results Higher interparental conflict since birth was associated with infants showing stronger connectivity between two core DMN regions, the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC). PCC to amygdala connectivity was also increased. Stronger PCC-aMPFC connectivity mediated between higher conflict and higher negative infant emotionality. Conclusions The developing DMN may be an important marker for effects of ELS with relevance for emotional development and subsequent mental health. Increasing understanding of the associations between common forms of family stress and emerging functional brain networks has potential to inform intervention efforts to improve mental health outcomes. PMID:25809052

White Matter Maturation Supports the Development of Reasoning Ability Through its Influence on Processing Speed

PubMed Central

Ferrer, E.; Whitaker, K.J.; Steele, J.; Green, C.T.; Wendelken, C.; Bunge, S.A.

2013-01-01

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability. PMID:24118718

Prenatal Influences on Human Sexual Orientation: Expectations versus Data.

PubMed

Breedlove, S Marc

2017-08-01

In non-human vertebrate species, sexual differentiation of the brain is primarily driven by androgens such as testosterone organizing the brains of males in a masculine fashion early in life, while the lower levels of androgen in developing females organize their brains in a feminine fashion. These principles may be relevant to the development of sexual orientation in humans, because retrospective markers of prenatal androgen exposure, namely digit ratios and otoacoustic emissions, indicate that lesbians, on average, were exposed to greater prenatal androgen than were straight women. Thus, the even greater levels of prenatal androgen exposure experienced by fetal males may explain why the vast majority of them grow up to be attracted to women. However, the same markers indicate no significant differences between gay and straight men in terms of average prenatal androgen exposure, so the variance in orientation in men cannot be accounted for by variance in prenatal androgen exposure, but may be due to variance in response to prenatal androgens. These data contradict several popular notions about human sexual orientation. Sexual orientation in women is said to be fluid, sometimes implying that only social influences in adulthood are at work, yet the data indicate prenatal influences matter as well. Gay men are widely perceived as under-masculinized, yet the data indicate they are exposed to as much prenatal androgen as straight men. There is growing sentiment to reject "binary" conceptions of human sexual orientations, to emphasize instead a spectrum of orientations. Yet the data indicate that human sexual orientation is sufficiently polarized that groups of lesbians, on average, show evidence of greater prenatal androgen exposure than groups of straight women, while groups of gay men have, on average, a greater proportion of brothers among their older siblings than do straight men.

Somatosensory responses in a human motor cortex

PubMed Central

Donoghue, John P.; Hochberg, Leigh R.

2013-01-01

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. PMID:23343902

Neurotransmitters couple brain activity to subventricular zone neurogenesis

PubMed Central

Young, Stephanie Z.; Taylor, M. Morgan; Bordey, Angélique

2011-01-01

Adult neurogenesis occurs in two privileged microenvironments, the hippocampal subgranular zone of the dentate gyrus and the subventricular zone (SVZ) along the lateral ventricle. This review focuses on accumulating evidence suggesting that the activity of specific brain regions or bodily states influences SVZ cell proliferation and neurogenesis. Neuromodulators such as dopamine and serotonin have been shown to have long-range effects through neuronal projections into the SVZ. Local GABA and glutamate signaling have demonstrated effects on SVZ proliferation and neurogenesis, but an extra-niche source of these neurotransmitters remains to be explored and options will be discussed. There is also accumulating evidence that diseases and bodily states such as Alzheimer's disease, seizures, sleep, and pregnancy influence SVZ cell proliferation. With such complex behavior and environmentally-driven factors that control subregion-specific activity, it will become necessary to account for overlapping roles of multiple neurotransmitter systems on neurogenesis when developing cell therapies or drug treatments. PMID:21395856

Food reward in the absence of taste receptor signaling.

PubMed

de Araujo, Ivan E; Oliveira-Maia, Albino J; Sotnikova, Tatyana D; Gainetdinov, Raul R; Caron, Marc G; Nicolelis, Miguel A L; Simon, Sidney A

2008-03-27

Food palatability and hedonic value play central roles in nutrient intake. However, postingestive effects can influence food preferences independently of palatability, although the neurobiological bases of such mechanisms remain poorly understood. Of central interest is whether the same brain reward circuitry that is responsive to palatable rewards also encodes metabolic value independently of taste signaling. Here we show that trpm5-/- mice, which lack the cellular machinery required for sweet taste transduction, can develop a robust preference for sucrose solutions based solely on caloric content. Sucrose intake induced dopamine release in the ventral striatum of these sweet-blind mice, a pattern usually associated with receipt of palatable rewards. Furthermore, single neurons in this same ventral striatal region showed increased sensitivity to caloric intake even in the absence of gustatory inputs. Our findings suggest that calorie-rich nutrients can directly influence brain reward circuits that control food intake independently of palatability or functional taste transduction.

Evaluation of the factors influencing brain language laterality in presurgical planning.

PubMed

Batouli, Seyed Amir Hossein; Hasani, Nafiseh; Gheisari, Sara; Behzad, Ebrahim; Oghabian, Mohammad Ali

2016-10-01

Brain lesions cause functional deficits, and one treatment for this condition is lesion resection. In most cases, presurgical planning (PSP) and the information from laterality indices are necessary for maximum preservation of the critical functions after surgery. Language laterality index (LI) is reliably estimated using functional magnetic resonance imaging (fMRI); however, this measure is under the influence of some external factors. In this study, we investigated the influence of a number of factors on language LI, using data from 120 patients (mean age=35.65 (±13.4) years) who underwent fMRI for PSP. Using two proposed language tasks from our previous works, brain left hemisphere was showed to be dominant for the language function, although a higher LI was obtained using the "Word Generation" task, compared to the "Reverse Word Reading". In addition, decline of LIs with age, and lower LI when the lesion invaded brain language area were observed. Meanwhile, gender, lesion side (affected hemisphere), LI calculation strategy, and fMRI analysis Z-values did not statistically show any influences on the LIs. Although fMRI is widely used to estimate language LI, it is shown here that in order to present a reliable language LI and to correctly select the dominant hemisphere of the brain, the influence of external factors should be carefully considered. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

[Clinical predictors correlated to outcome of war missile penetrating brain injury].

PubMed

Splavski, Bruno; Vranković, Duro; Saftić, Robert; Muzević, Dario; Kosuta, Maja; Gmajnić, Rudika

2006-09-01

The purpose of this retrospective study was to review and discuss the outcome of surgical management and other clinical predictors influencing the prognosis of war missile penetrating brain injuries. To determine clinical predictors that influence the prognosis of war missile penetrating brain injury, 126 surgically treated patients who had sustained such an injury during the two-year period of war in Croatia (1991-1993) were retrospectively analyzed. Investigated clinical features were: Glasgow Coma Scale (GCS) score on admission; extent of brain injury; time between injury and hospital admission; presence of intracranially retained foreign bodies or bone fragments; development of postinjury and posttraumatic complications; and Glasgow Outcome Score (GOS) at six-month follow up. The data were statistically analyzed. Sixty-seven patients survived penetrating missile brain injury, in most of them with GCS score above 8 on admission. The mean time interval to hospital admission in this group of patients was less than two hours. Twelve of 67 patients developed different complications. All patients recovered well according to GOS (GOS 5 and 4) at six-month follow up. Fifty-nine patients died. The wounded who were in moribund state on the hospital admission (n = 11), and those who died during surgery (n = 8) were excluded from the analysis. The remaining 40 patients who did not survive were analyzed. The majority of them had GCS score 3-8 on admission. They mostly sustained bilateral hemispheric lesion, and/or ventricular lesion, and developed brain edema. The mean time interval between injury and hospital admission was over two hours in this group of patients. Postoperative complication developed in 9 of 40 patients. The patients with GCS score exceeding 8 had by far more favorable outcome in comparison to those with GCS score less than 8. Considering the extent of injury, patients suffering unihemispheric brain wounds had a more favorable outcome than those with lesions of both hemispheres, and particularly those with transventricular lesions. The time between injury and hospital admission proved to be another important prognostic factor. The majority of patients admitted up to one hour of injury survived, while two thirds of those admitted between one and three hours of injury succumbed. The presence of intracranially retained foreign bodies and bone fragments, and postinjury and postoperative complications implied worse outcome in comparison with their absence. The state of consciousness on admission was the most sensitive criterion as far as the prognosis is concerned. The outcome also depended on the extent of brain damage since the wounds associated with a high mortality rate were predominantly bihemispheric. Concerning survival, the time between injury and hospital admission also appeared to be important, as well as intracranially retained foreign bodies and bone fragments, and development of complications. There was no relationship between the presence of retained fragments and development of infection, suggesting that it is not necessary to reoperate for retained fragments. We assume that early surgery is essential for treatment outcome, although it is not necessary to reoperate for retained fragments.

The human brain—from cells to society

PubMed Central

Hoogland, Eva; Patten, Iain; Berghmans, Stephane

2013-01-01

In December 2011, the European Science Foundation (ESF) brought together experts from a wide range of disciplines to discuss the issues that will influence the development of a healthier, more brain-aware European society. This perspective summarizes the main outcomes of that discussion and highlights important considerations to support improved mental health in Europe, including: The development of integrated neuropsychotherapeutic approaches to the treatment of psychiatric disorders.The development of more valid disease models for research into psychiatric disorders.An improved understanding of the relationship between biology and environment, particularly in relation to developmental plasticity and emerging pathology.More comparative studies to explore how scientific concepts relating to the human brain are received and understood in different sociocultural contexts.Research into the legal and ethical implications of recent developments in the brain sciences, including behavioral screening and manipulation, and emerging neurotechnologies. The broad geographical spread of the consulted experts across the whole of Europe, along with the wide range of disciplines they represent, gives these conclusions a strong scientific and pan-European endorsement. The next step will be to look closely into these five selected topics, in terms of research strategy, science policy, societal implications, and legal and ethical frameworks. PMID:23966920

Metal-based nanoparticle interactions with the nervous system: the challenge of brain entry and the risk of retention in the organism.

PubMed

Yokel, Robert; Grulke, Eric; MacPhail, Robert

2013-01-01

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical-chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in vivo methods, and very few human studies. The routes of uptake into the nervous system and mechanisms of nanoparticle uptake by cells are presented with examples. Brain nanoparticle uptake inversely correlates with size. The influence of shape has not been reported. Surface charge has not been clearly shown to affect flux across the blood-brain barrier. There is very little evidence for metal-based nanoparticle distribution into brain parenchyma. Metal-based nanoparticle disruption of the blood-brain barrier and adverse brain changes have been shown, and are more pronounced for spheres than rods. Study concentrations need to be put in exposure contexts. Work with dorsal root ganglion cells and brain cells in vitro show the potential for metal-based nanoparticles to produce toxicity. Interpretation of these results must consider the ability of nanoparticles to distribute across the barriers protecting the nervous system. Effects of the persistence of poorly soluble metal-based nanoparticles are of particular concern. Copyright © 2013 Wiley Periodicals, Inc.

From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation.

PubMed

Bajic, Juliana E; Johnston, Ian N; Howarth, Gordon S; Hutchinson, Mark R

2018-01-01

The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

PubMed

Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

2016-01-01

Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

Foundational perspectives on causality in large-scale brain networks

NASA Astrophysics Data System (ADS)

Mannino, Michael; Bressler, Steven L.

2015-12-01

A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical likelihood that a change in the activity of one neuronal population affects the activity in another. We argue that these measures access the inherently probabilistic nature of causal influences in the brain, and are thus better suited for large-scale brain network analysis than are DC-based measures. Our work is consistent with recent advances in the philosophical study of probabilistic causality, which originated from inherent conceptual problems with deterministic regularity theories. It also resonates with concepts of stochasticity that were involved in establishing modern physics. In summary, we argue that probabilistic causality is a conceptually appropriate foundation for describing neural causality in the brain.

Foundational perspectives on causality in large-scale brain networks.

PubMed

Mannino, Michael; Bressler, Steven L

2015-12-01

A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical likelihood that a change in the activity of one neuronal population affects the activity in another. We argue that these measures access the inherently probabilistic nature of causal influences in the brain, and are thus better suited for large-scale brain network analysis than are DC-based measures. Our work is consistent with recent advances in the philosophical study of probabilistic causality, which originated from inherent conceptual problems with deterministic regularity theories. It also resonates with concepts of stochasticity that were involved in establishing modern physics. In summary, we argue that probabilistic causality is a conceptually appropriate foundation for describing neural causality in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

A centric/non-centric impact protocol and finite element model methodology for the evaluation of American football helmets to evaluate risk of concussion.

PubMed

Post, Andrew; Oeur, Anna; Walsh, Evan; Hoshizaki, Blaine; Gilchrist, Michael D

2014-01-01

American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur. The purpose of this study was to investigate a proposed three-dimensional impact protocol for use in evaluating football helmets. The dynamic responses resulting from centric and non-centric impact conditions were examined to ascertain the influence they have on brain deformations in different functional regions of the brain that are linked to concussive symptoms. A centric and non-centric protocol was used to impact an American football helmet; the resulting dynamic response data was used in conjunction with a three-dimensional finite element analysis of the human brain to calculate brain tissue deformation. The direction of impact created unique loading conditions, resulting in peaks in different regions of the brain associated with concussive symptoms. The linear and rotational accelerations were not predictive of the brain deformation metrics used in this study. In conclusion, the test protocol used in this study revealed that impact conditions influences the region of loading in functional regions of brain tissue that are associated with the symptoms of concussion. The protocol also demonstrated that using brain deformation metrics may be more appropriate when evaluating risk of concussion than using dynamic response data alone.

More than a drainage fluid: the role of CSF in signaling in the brain and other effects on brain tissue.

PubMed

Illes, Sebastian

2017-01-01

Current progress in neuroscience demonstrates that the brain is not an isolated organ and is influenced by the systemic environment and extracerebral processes within the body. In view of this new concept, blood and cerebrospinal fluid (CSF) are important body fluids linking extracerebral and intracerebral processes. For decades, substantial evidence has been accumulated indicating that CSF modulates brain states and influences behavior as well as cognition. This chapter provides an overview of how CSF directly modulates the function of different types of brain cells, such as neurons, neural stem cells, and CSF-contacting cells. Alterations in CSF content occur in most pathologic central nervous system (CNS) conditions. In a classic view, the function of CSF is to drain waste products and detrimental factors derived from diseased brain parenchyma. This chapter presents examples for how intra- and extracerebral pathologic processes lead to alterations in the CSF content. Current knowledge about how pathologically altered CSF influences the functionality of brain cells will be presented. Thereby, it becomes evident that CSF has more than a drainage function and has a causal role for the etiology and pathogenesis of different CNS diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain catechol synthesis - Control by brain tyrosine concentration

NASA Technical Reports Server (NTRS)

Wurtman, R. J.; Larin, F.; Mostafapour, S.; Fernstrom, J. D.

1974-01-01

Brain catechol synthesis was estimated by measuring the rate at which brain dopa levels rose following decarboxylase inhibition. Dopa accumulation was accelerated by tyrosine administration, and decreased by treatments that lowered brain tyrosine concentrations (for example, intraperitoneal tryptophan, leucine, or parachlorophenylalanine). A low dose of phenylalanine elevated brain tyrosine without accelerating dopa synthesis. Our findings raise the possibility that nutritional and endocrine factors might influence brain catecholamine synthesis by controlling the availability of tyrosine.

Prefrontal cortex NG2 glia undergo a developmental switch in their responsiveness to exercise.

PubMed

Tomlinson, Lyl; Huang, Po Hsuan; Colognato, Holly

2018-03-22

Aerobic exercise is known to influence brain function, e.g., enhancing executive function in both children and adults, with many of these influences being attributed to alterations in neurogenesis and neuronal function. Yet oligodendroglia in adult brains have also been reported to be highly responsive to exercise, including in the prefrontal cortex (PFC), a late myelinating region implicated in working memory. However, whether exercise affects oligodendroglia or myelination in juveniles, either in the PFC or in other brain regions, remains unknown. To address this, both juvenile and young adult mice were provided free access to running wheels for four weeks followed by an analysis of oligodendrocyte development and myelination in the PFC and the corpus callosum, a major white matter tract. Working memory and PFC NG2+ cell development were both affected by exercise in juvenile mice, yet surprisingly these exercise-mediated effects were distinct in juveniles and young adults. In the PFC, NG2+ cell proliferation was increased in exercising juveniles, but not young adults, whereas newly-born oligodendrocyte production was increased in exercising young adults, but not juveniles. Although no overall changes in myelin genes were found, elevated levels of Monocarboxylate Transporter 1, a glial lactate transporter important during active myelination, were found in the PFC of exercising young adults. Overall our findings reveal that long-term exercise modulates PFC glial development and does so differentially in juvenile and young adult mice, providing insight into the cellular responses that may underlie cognitive benefits to teenagers and young adults in response to exercise. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Development of a high-throughput brain slice method for studying drug distribution in the central nervous system.

PubMed

Fridén, Markus; Ducrozet, Frederic; Middleton, Brian; Antonsson, Madeleine; Bredberg, Ulf; Hammarlund-Udenaes, Margareta

2009-06-01

New, more efficient methods of estimating unbound drug concentrations in the central nervous system (CNS) combine the amount of drug in whole brain tissue samples measured by conventional methods with in vitro estimates of the unbound brain volume of distribution (V(u,brain)). Although the brain slice method is the most reliable in vitro method for measuring V(u,brain), it has not previously been adapted for the needs of drug discovery research. The aim of this study was to increase the throughput and optimize the experimental conditions of this method. Equilibrium of drug between the buffer and the brain slice within the 4 to 5 h of incubation is a fundamental requirement. However, it is difficult to meet this requirement for many of the extensively binding, lipophilic compounds in drug discovery programs. In this study, the dimensions of the incubation vessel and mode of stirring influenced the equilibration time, as did the amount of brain tissue per unit of buffer volume. The use of cassette experiments for investigating V(u,brain) in a linear drug concentration range increased the throughput of the method. The V(u,brain) for the model compounds ranged from 4 to 3000 ml . g brain(-1), and the sources of variability are discussed. The optimized setup of the brain slice method allows precise, robust estimation of V(u,brain) for drugs with diverse properties, including highly lipophilic compounds. This is a critical step forward for the implementation of relevant measurements of CNS exposure in the drug discovery setting.

Identification of a set of genes showing regionally enriched expression in the mouse brain

PubMed Central

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa LC; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven JM

2008-01-01

Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression. PMID:18625066

Identification of a set of genes showing regionally enriched expression in the mouse brain.

PubMed

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa L C; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven J M

2008-07-14

The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

Estimated maximal and current brain volume predict cognitive ability in old age

PubMed Central

Royle, Natalie A.; Booth, Tom; Valdés Hernández, Maria C.; Penke, Lars; Murray, Catherine; Gow, Alan J.; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.

2013-01-01

Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging. PMID:23850342

[On factors that effect the variability of central mechanisms of bilingualism].

PubMed

Kruchinina, O V; Gal'perina, E I; Kats, E É; Shepoval'nikov, A N

2012-01-01

The article discusses the probable role of many factors that determine the individual variety of neurophysiological mechanisms, which provide the opportunity to learn and free use two or more languages. The formation of a speech functions is affected by both the general factors for bilinguals and monolinguals, as well as the specific characteristic of the situation of bilingualism. The general factors include genetic and environmental impact of explaining the diversity of individual options for the development of morphofunctional organization of speech functions. A bilinguals, obviously, have even more wide variance of the central maintenance of speech activity, due to the combination of different conditions that influence the language environment, which include the age of the second language acquisition, the language proficiency, linguistic closeness of the languages, the method of their acquisition, intensity of use and the scope of application of each of the languages. The influence of these factors can mediates in different ways by the individual characteristics of the bilingual's brain. Being exposed to two languages from the first days of life, the child uses for the development of speech skills of the unique features of the brain, which are available only in the initial stages of postnatal ontogenesis. In older age mastering a second language requires much more effort, when, as maturation, the brain acquires new additional possibilities, but permanently lose that special "bonus", which nature gives a small child only in the first months of life. Large individual variability patterns of activation of the cortex when verbal activity in late bilingual" compared with the "early", allows to assume, that the brain of "late bilingual", mastering a new language, forced to operate a large number of backup mechanisms, and this is reflected in the increase of variation in the cerebral processes, responsible for providing of speech functions. In addition, there is serious reason to believe that learning a second language contributes to the expansion of the functional capabilities of the brain and creates the basis for a successful cognitive activity.

Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer's disease.

PubMed

Lauzon, Marc-Antoine; Daviau, Alex; Marcos, Bernard; Faucheux, Nathalie

2015-05-28

The number of people diagnosed with Alzheimer's disease (AD) is increasing steadily as the world population ages, thus creating a huge socio-economic burden. Current treatments have only transient effects and concentrate on a single aspect of AD. There is much evidence suggesting that growth factors (GFs) have a great therapeutic potential and can play on all AD hallmarks. Because GFs are prone to denaturation and clearance, a delivery system is required to ensure protection and a sustainable delivery. This review provides information about the latest advances in the development of GF delivery systems (GFDS) targeting the brain in terms of in vitro and in vivo effects in the context of AD and discusses new strategies designed to increase the availability and the specificity of GFs to the brain. This paper also discusses, on a mechanistic level, the different delivery hurdles encountered by the carrier or the GF itself from its injection site up to the brain tissue. The major mass transport phenomena influencing the delivery systems targeting the brain are addressed and insights are given about how mechanistic mathematical frameworks can be developed to use and optimize them. Copyright © 2015. Published by Elsevier B.V.

The neurobiology of the emotional adolescent: From the inside out

PubMed Central

Guyer, Amanda E.; Silk, Jennifer S.; Nelson, Eric E.

2016-01-01

Adolescents are commonly portrayed as highly emotional, with their behaviors often hijacked by their emotions. Research on the neural substrates of adolescent affective behavior is beginning to paint a more nuanced picture of how neurodevelopmental changes in brain function influence affective behavior, and how these influences are modulated by external factors in the environment. Recent neurodevelopmental models suggest that the brain is designed to promote emotion regulation, learning, and affiliation across development, and that affective behavior reciprocally interacts with age-specific social demands and different social contexts. In this review, we discuss current findings on neurobiological mechanisms of adolescents’ affective behavior and highlight individual differences in and social-contextual influences on adolescents’ emotionality. Neurobiological mechanisms of affective processes related to anxiety and depression are also discussed as examples. As the field progresses, it will be critical to test new hypotheses generated from the foundational empirical and conceptual work and to focus on identifying more precisely how and when neural networks change in ways that promote or thwart adaptive affective behavior during adolescence. PMID:27506384

Sleep spindles and cognitive performance across adolescence: A meta-analytic review.

PubMed

Reynolds, C M; Short, M A; Gradisar, M

2018-07-01

Higher sleep spindle activity generally relates to better cognitive performance in adults, while studies in children often show the opposite. As children become young adults, there is rapid brain maturation and development of higher-order cognitive functions, and therefore investigations within this age group may elucidate the relationship between spindles and cognition in this developmental period. Twelve studies published between 2009 and 2016 were identified. Meta-analyses revealed a positive relationship between spindles and cognition overall (r = 0.27), however effects varied depending on cognitive domain. Moderate positive relationships were seen for fluid IQ (r = 0.44), working memory/executive function (r = 0.40) and speed/accuracy (r = 0.33), while full IQ/verbal IQ was not significantly associated (r = -0.05). Meta-regressions indicated cognitive domain and spindle characteristic had a small influence over effect sizes, while age and gender did not have a significant influence. The relationship between spindles and cognition in adolescents is likely influenced by individual neural makeup and brain maturation. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Cerebral motor function in very premature-at-birth adolescents: a brain stimulation exploration of kangaroo mother care effects.

PubMed

Schneider, Cyril; Charpak, Nathalie; Ruiz-Peláez, Juan G; Tessier, Réjean

2012-10-01

  Given that prematurity has deleterious effects on brain networking development beyond childhood, the study explored whether an early intervention such as Kangaroo Mother Care (KMC) in very preterm preemies could have influenced brain motor function up to adolescence.   Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) of 39 adolescents born very prematurely (<33 weeks' gestational age, 21 having received KMC after birth, 18 Controls with no KMC) and nine adolescents born at term (>37 weeks' gestational age, >2500 g) to assess the functional integrity of motor circuits in each hemisphere (motor planning) and between hemispheres (callosal function).   All TMS outcomes were similar between KMC and term adolescents, with typical values as in healthy adults, and better than in Controls. KMC adolescents presented faster conduction times revealing more efficient M1 cell synchronization (p < 0.05) and interhemispheric transfer time (p < 0.0001), more frequent inhibitory processes with a better control between hemispheres (p < 0.0001).   The enhanced synchronization, conduction times and connectivity of cerebral motor pathways in the KMC group suggests that the Kangaroo Mother Care positively influenced the premature brain networks and synaptic efficacy up to adolescence. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Divergence of brain and retinal anatomy and histology in pelagic antarctic notothenioid fishes of the sister taxa Dissostichus and Pleuragramma.

PubMed

Eastman, Joseph T; Lannoo, Michael J

2011-04-01

The neutrally buoyant Antarctic fishes of the sister taxa Dissostichus (D. eleginoides and D. mawsoni) and Pleuragramma antarcticum diverged early in the notothenioid radiation and filled different niches in the pelagic realm of the developing Southern Ocean. To assess the influence of phylogenetic and ecological factors in shaping neural morphology in these taxa, we studied the anatomy and histology of the brains and retinae, and determined the proportional weights of brain regions. With the brain of the non-Antarctic sister taxon Eleginops maclovinus as plesiomorphic, statistically significant departures in the brains of the two Antarctic taxa include reduction of the corpus cerebelli and expansion of the mesencephalon and medulla. Compared to Eleginops, both species also have a relatively smaller telencephalon, although this is significant only in Dissostichus. There are a number of apomorphic features in the brain of Pleuragramma including reduced olfactory nerves and bulbs, an extremely small corpus cerebelli and an expanded mesencephalon. Although there is not a significant difference in the relative weights of the medulla in the two taxa, the prominence of the eminentia granularis and bulging cap-like appearance of the crista cerebellaris are distinctive in Pleuragramma. Brain histology of Dissostichus and Pleuragramma reflects typical perciform patterns and the two species of Dissostichus are histologically identical. Lateral compression in Pleuragramma and notable lobation in Dissostichus also contribute to differences between the taxa. Compression in Pleuragramma is attributable to convergence on an anchovy/herring body shape and to the relatively large brain in this small fish. The less prominent pattern of lobation of the telencephalon, inferior lobes and corpus cerebelli in Pleuragramma probably reflects underlying histology, specifically a reduction in cellularity of the neuropil in the nuclei and lobes. The retinal histology of Dissostichus and Pleuragramma encompasses the extremes seen in Antarctic notothenioids. Dissostichus has a thin scotopic retina with few cones and a high degree of summation. The retina of Pleuragramma is thick and cellular with many small single cones and rods and resembles that of Eleginops. Pedomorphy has not influenced brain morphology in these species but Pleuragramma has superficial neuromasts that are pedomorphic. Although Dissostichus and Pleuragramma are sympatric in the water column, their brains and retinae are highly divergent and reflect the influences of both phylogeny and ecological partitioning of the pelagic realm. Compared to Eleginops, the relatively smaller corpus cerebelli but relatively larger medulla probably indicates, respectively, reduced activity levels of notothenioids in subzero temperatures and expansion of the mechanosensory lateral line system as a supplement to vision under conditions of reduced light. Compared to Dissostichus, Pleuragramma has reduced olfactory bulbs and corpus cerebelli and an expanded mesencephalon. The reduction of the corpus to a small round knob is consistent with physiological parameters and video observations suggesting that, although pelagic, it is relatively inactive. Because mesencephalic weights also include the valvula cerebelli, the relatively large value for Pleuragramma may be attributable to its role in integration and sensorimotor coordination of information from the highly cellular duplex retina and to integration of signals from thewell-developed octavolateralis system. The brain of Dissostichus displays considerable persistent morphology in its overall resemblance to that of Eleginops, especially the large olfactory bulbs and the relatively large caudally projecting corpus, and Dissostichus exhibits olfactory tracking ability and migratory behavior in common with Eleginops. Copyright © 2011 Wiley-Liss, Inc.

Neonatal treatment with monosodium glutamate lastingly facilitates spreading depression in the rat cortex.

PubMed

Lima, Cássia Borges; Soares, Geórgia de Sousa Ferreira; Vitor, Suênia Marcele; Castellano, Bernardo; Andrade da Costa, Belmira Lara da Silveira; Guedes, Rubem Carlos Araújo

2013-09-17

Monosodium glutamate (MSG) is a neuroexcitatory amino acid used in human food to enhance flavor. MSG can affect the morphological and electrophysiological organization of the brain. This effect is more severe during brain development. Here, we investigated the electrophysiological and morphological effects of MSG in the developing rat brain by characterizing changes in the excitability-related phenomenon of cortical spreading depression (CSD) and microglial reaction. From postnatal days 1-14, Wistar rat pups received 2 or 4 g/kg MSG (groups MSG-2 and MSG-4, respectively; n=9 in each group), saline (n=10) or no treatment (naïve group; n=5) every other day. At 45-60 days, CSD was recorded on two cortical points for 4h. The CSD parameters velocity, and amplitude and duration of the negative potential change were calculated. Fixative-perfused brain sections were immunolabeled with anti-IBA-1 antibodies to identify and quantify cortical microglia. MSG-4 rats presented significantly higher velocities (4.59 ± 0.34 mm/min) than the controls (saline, 3.84 ± 0.20mm/min; naïve, 3.71 ± 0.8mm/min) and MSG-2 group (3.75 ± 0.10mm/min). The amplitude (8.8 ± 2.2 to 11.2 ± 1.9 mV) and duration (58.2 ± 7.1 to 73.6 ± 6.0s) of the negative slow potential shift was similar in all groups. MSG-treatment dose-dependently increased the microglial immunolabeling. The results demonstrate a novel, dose-dependent action of MSG in the developing brain, characterized by acceleration of CSD and significant microglial reaction in the cerebral cortex. The CSD effect indicates that MSG can influence cortical excitability, during brain development, as evaluated by CSD acceleration. Data suggest caution when consuming MSG, especially in developing organisms. © 2013.

Thermodynamic laws apply to brain function.

PubMed

Salerian, Alen J

2010-02-01

Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

PubMed

Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

2015-05-01

The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

PubMed Central

Jahanshad, Neda; Kochunov, Peter; Sprooten, Emma; Mandl, René C.; Nichols, Thomas E.; Almassy, Laura; Blangero, John; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Duggirala, Ravi; Fox, Peter T.; Hong, L. Elliot; Landman, Bennett A.; Martin, Nicholas G.; McMahon, Katie L.; Medland, Sarah E.; Mitchell, Braxton D.; Olvera, Rene L.; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Hulshoff Pol, Hilleke E.; Bastin, Mark E.; McIntosh, Andrew M.; Deary, Ian J.; Thompson, Paul M.; Glahn, David C.

2013-01-01

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/). PMID:23629049

Diffusion in Brain Extracellular Space

PubMed Central

Syková, Eva; Nicholson, Charles

2009-01-01

Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecules in the brain. Deviations from the equation reveal loss of molecules across the blood-brain barrier, through cellular uptake, binding or other mechanisms. Early diffusion measurements used radiolabeled sucrose and other tracers. Presently, the real-time iontophoresis (RTI) method is employed for small ions and the integrative optical imaging (IOI) method for fluorescent macromolecules, including dextrans or proteins. Theoretical models and simulations of the ECS have explored the influence of ECS geometry, effects of dead-space microdomains, extracellular matrix and interaction of macromolecules with ECS channels. Extensive experimental studies with the RTI method employing the cation tetramethylammonium (TMA) in normal brain tissue show that the volume fraction of the ECS typically is about 20% and the tortuosity about 1.6 (i.e. free diffusion coefficient of TMA is reduced by 2.6), although there are regional variations. These parameters change during development and aging. Diffusion properties have been characterized in several interventions, including brain stimulation, osmotic challenge and knockout of extracellular matrix components. Measurements have also been made during ischemia, in models of Alzheimer's and Parkinson's diseases and in human gliomas. Overall, these studies improve our conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment. Knowledge of ECS diffusion properties are valuable in contexts ranging from understanding extrasynaptic volume transmission to the development of paradigms for drug delivery to the brain. PMID:18923183

An exercise-based randomized controlled trial on brain, cognition, physical health and mental health in overweight/obese children (ActiveBrains project): Rationale, design and methods.

PubMed

Cadenas-Sánchez, Cristina; Mora-González, José; Migueles, Jairo H; Martín-Matillas, Miguel; Gómez-Vida, José; Escolano-Margarit, María Victoria; Maldonado, José; Enriquez, Gala María; Pastor-Villaescusa, Belén; de Teresa, Carlos; Navarrete, Socorro; Lozano, Rosa María; de Dios Beas-Jiménez, Juan; Estévez-López, Fernando; Mena-Molina, Alejandra; Heras, María José; Chillón, Palma; Campoy, Cristina; Muñoz-Hernández, Victoria; Martínez-Ávila, Wendy Daniela; Merchan, María Elisa; Perales, José C; Gil, Ángel; Verdejo-García, Antonio; Aguilera, Concepción M; Ruiz, Jonatan R; Labayen, Idoia; Catena, Andrés; Ortega, Francisco B

2016-03-01

The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and understanding how brain and cognition function can be stimulated by environmental factors, such as exercise, and particularly to study whether physical exercise influences brain development in early ages. The present study, namely the ActiveBrains project, aims to examine the effects of a physical exercise programme on brain and cognition, as well as on selected physical and mental health outcomes in overweight/obese children. A total of 100 participants aged 8 to 11 years are randomized into an exercise group (N=50) or a control group (N=50). The intervention lasts 20-weeks, with 3-5 sessions per week of 90 min each, and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises. The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a subsample. Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings. Secondary outcomes include physical health outcomes (e.g. physical fitness, body fatness, bone mass and lipid-metabolic factors) and mental health outcomes (e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression). This project will substantially contribute to the existing knowledge and will have an impact on societies, since early stimulation of brain development might have long lasting consequences on cognitive performance, academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health. Clinical trials. Gov identifier: NCT02295072. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection.

PubMed

Woods, Tyson A; Du, Min; Carmody, Aaron; Peterson, Karin E

2015-12-30

Monocyte infiltration into the CNS is a hallmark of several viral infections of the central nervous system (CNS), including retrovirus infection. Understanding the factors that mediate monocyte migration in the CNS is essential for the development of therapeutics that can alter the disease process. In the current study, we found that neuropeptide Y (NPY) suppressed monocyte recruitment to the CNS in a mouse model of polytropic retrovirus infection. NPY(-/-) mice had increased incidence and kinetics of retrovirus-induced neurological disease, which correlated with a significant increase in monocytes in the CNS compared to wild-type mice. Both Ly6C(hi) inflammatory and Ly6C(lo) alternatively activated monocytes were increased in the CNS of NPY(-/-) mice following virus infection, suggesting that NPY suppresses the infiltration of both cell types. Ex vivo analysis of myeloid cells from brain tissue demonstrated that infiltrating monocytes expressed high levels of the NPY receptor Y2R. Correlating with the expression of Y2R on monocytes, treatment of NPY(-/-) mice with a truncated, Y2R-specific NPY peptide suppressed the incidence of retrovirus-induced neurological disease. These data demonstrate a clear role for NPY as a negative regulator of monocyte recruitment into the CNS and provide a new mechanism for suppression of retrovirus-induced neurological disease. Monocyte recruitment to the brain is associated with multiple neurological diseases. However, the factors that influence the recruitment of these cells to the brain are still not well understood. In the current study, we found that neuropeptide Y, a protein produced by neurons, affected monocyte recruitment to the brain during retrovirus infection. We show that mice deficient in NPY have increased influx of monocytes into the brain and that this increase in monocytes correlates with neurological-disease development. These studies provide a mechanism by which the nervous system, through the production of NPY, can suppress monocyte trafficking to the brain and reduce retrovirus-induced neurological disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Weighted and directed interactions in evolving large-scale epileptic brain networks

NASA Astrophysics Data System (ADS)

Dickten, Henning; Porz, Stephan; Elger, Christian E.; Lehnertz, Klaus

2016-10-01

Epilepsy can be regarded as a network phenomenon with functionally and/or structurally aberrant connections in the brain. Over the past years, concepts and methods from network theory substantially contributed to improve the characterization of structure and function of these epileptic networks and thus to advance understanding of the dynamical disease epilepsy. We extend this promising line of research and assess—with high spatial and temporal resolution and using complementary analysis approaches that capture different characteristics of the complex dynamics—both strength and direction of interactions in evolving large-scale epileptic brain networks of 35 patients that suffered from drug-resistant focal seizures with different anatomical onset locations. Despite this heterogeneity, we find that even during the seizure-free interval the seizure onset zone is a brain region that, when averaged over time, exerts strongest directed influences over other brain regions being part of a large-scale network. This crucial role, however, manifested by averaging on the population-sample level only - in more than one third of patients, strongest directed interactions can be observed between brain regions far off the seizure onset zone. This may guide new developments for individualized diagnosis, treatment and control.

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

PubMed Central

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

2015-01-01

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

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

PubMed

Raichlen, David A; Polk, John D

2013-01-07

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

The meningeal lymphatic system: a route for HIV brain migration?

PubMed

Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S

2016-06-01

Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

Apollo’s gift: new aspects of neurologic music therapy

PubMed Central

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music’s ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. PMID:25725918

Apollo's gift: new aspects of neurologic music therapy.

PubMed

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music's ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. © 2015 Elsevier B.V. All rights reserved.

Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

PubMed Central

Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

2015-01-01

Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

Nicotine and the adolescent brain.

PubMed

Yuan, Menglu; Cross, Sarah J; Loughlin, Sandra E; Leslie, Frances M

2015-08-15

Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Dysbindin modulates brain function during visual processing in children.

PubMed

Mechelli, A; Viding, E; Kumar, A; Pettersson-Yeo, W; Fusar-Poli, P; Tognin, S; O'Donovan, M C; McGuire, P

2010-01-01

Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain function is poorly understood. It has been proposed that DTNBP1 may be associated with differences in visual processing. To test this, we examined the impact on visual processing in 61 healthy children aged 10-12 years of a genetic variant in DTNBP1 (rs2619538) that was common to all schizophrenia associated haplotypes in an earlier UK-Irish study. We tested the hypothesis that carriers of the risk allele would show altered occipital cortical function relative to noncarriers. Functional Magnetic Resonance Imaging (fMRI) was used to measure brain responses during a visual matching task. The data were analysed using statistical parametric mapping and statistical inferences were made at p<0.05 (corrected for multiple comparisons). Relative to noncarriers, carriers of the risk allele had greater activation in the lingual, fusiform gyrus and inferior occipital gyri. In these regions DTNBP1 genotype accounted for 19%, 20% and 14% of the inter-individual variance, respectively. Our results suggest that that genetic variation in DTNBP1 is associated with differences in the function of brain areas that mediate visual processing, and that these effects are evident in young children. These findings are consistent with the notion that the DTNBP1 gene influences brain development and can thereby modulate vulnerability to schizophrenia.

Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

PubMed Central

Taylor, Sabrina R.; Smith, Colin M.; Keeley, Kristen L.; McGuone, Declan; Dodge, Carter P.; Duhaime, Ann-Christine; Costine, Beth A.

2016-01-01

Cortical contusions are a common type of traumatic brain injury (TBI) in children. Current knowledge of neuroblast response to cortical injury arises primarily from studies utilizing aspiration or cryoinjury in rodents. In infants and children, cortical impact affects both gray and white matter and any neurogenic response may be complicated by the large expanse of white matter between the subventricular zone (SVZ) and the cortex, and the large number of neuroblasts in transit along the major white matter tracts to populate brain regions. Previously, we described an age-dependent increase of neuroblasts in the SVZ in response to cortical impact in the immature gyrencephalic brain. Here, we investigate if neuroblasts target the injury, if white matter injury influences repair efforts, and if postnatal population of brain regions are disrupted. Piglets received a cortical impact to the rostral gyrus cortex or sham surgery at postnatal day (PND) 7, BrdU 2 days prior to (PND 5 and 6) or after injury (PND 7 and 8), and brains were collected at PND 14. Injury did not alter the number of neuroblasts in the white matter between the SVZ and the rostral gyrus. In the gray matter of the injury site, neuroblast density was increased in cavitated lesions, and the number of BrdU+ neuroblasts was increased, but comprised less than 1% of all neuroblasts. In the white matter of the injury site, neuroblasts with differentiating morphology were densely arranged along the cavity edge. In a ventral migratory stream, neuroblast density was greater in subjects with a cavitated lesion, indicating that TBI may alter postnatal development of regions supplied by that stream. Cortical impact in the immature gyrencephalic brain produced complicated and variable lesions, increased neuroblast density in cavitated gray matter, resulted in potentially differentiating neuroblasts in the white matter, and may alter the postnatal population of brain regions utilizing a population of neuroblasts that were born prior to PND 5. This platform may be useful to continue to study potential complications of white matter injury and alterations of postnatal population of brain regions, which may contribute to the chronic effects of TBI in children. PMID:27601978

Influence of Dexamethasone on O-(2-[18F]-Fluoroethyl)-L-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake.

PubMed

Stegmayr, Carina; Stoffels, Gabriele; Kops, Elena Rota; Lohmann, Philipp; Galldiks, Norbert; Shah, Nadim J; Neumaier, Bernd; Langen, Karl-Josef

2018-05-29

O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [ 18 F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR). [ 18 F]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [ 18 F]FET uptake in the normal brain (SUV brain ) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy. SUV brain of [ 18 F]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUV brain 1.33 ± 0.1 versus 1.06 ± 0.16 in male and 1.45 ± 0.25 versus 1.31 ± 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUV brain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBR max and TBR mean , which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBR max and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUV brain . Dexamethasone treatment appears to increase the [ 18 F]FET uptake in the normal brain. An effect on TBR max , TBR mean , and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [ 18 F]FET PET.

In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs).

PubMed

Gallagher, Erin; Minn, Il; Chambers, Janice E; Searson, Peter C

2016-07-11

Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs). To determine whether 2-PAM is a substrate for common brain efflux pumps, experiments were performed in the MDCKII-MDR1 cell line, transfected to overexpress the P-gp efflux pump, and the MDCKII-FLuc-ABCG2 cell line, transfected to overexpress the BCRP efflux pump. To determine how transcellular transport influences enzyme reactivation, we developed a modified transwell assay where the inhibited acetylcholinesterase enzyme, substrate, and reporter are introduced into the basolateral chamber. Enzymatic activity was inhibited using paraoxon and parathion. The permeability of 2-PAM is about 2 × 10(-6) cm s(-1) in MDCK cells and about 1 × 10(-6) cm s(-1) in BC1-hBMECs. Permeability is not influenced by pre-treatment with atropine. In addition, 2-PAM is not a substrate for the P-gp or BCRP efflux pumps. The low permeability explains poor brain penetration of 2-PAM and therefore the slow enzyme reactivation. This elucidates one of the reasons for the necessity of sustained intravascular (IV) infusion in response to organophosphate poisoning.

Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space

PubMed Central

Zuo, Xi-Nian; Xu, Ting; Jiang, Lili; Yang, Zhi; Cao, Xiao-Yan; He, Yong; Zang, Yu-Feng; Castellanos, F. Xavier; Milham, Michael P.

2013-01-01

While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test–retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo’s TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5 min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface). PMID:23085497

Learning and the Brain.

ERIC Educational Resources Information Center

Fishback, Sarah Jane

1999-01-01

Reviews research on the brain and memory, emotions, aging, and learning. Outlines practice implications: connect new learning to personal experiences, make sure learners are paying attention, recognize the role of emotions, and be aware that stimulation influences the aging brain. (SK)

Clinical study and numerical simulation of brain cancer dynamics under radiotherapy

NASA Astrophysics Data System (ADS)

Nawrocki, S.; Zubik-Kowal, B.

2015-05-01

We perform a clinical and numerical study of the progression of brain cancer tumor growth dynamics coupled with the effects of radiotherapy. We obtained clinical data from a sample of brain cancer patients undergoing radiotherapy and compare it to our numerical simulations to a mathematical model of brain tumor cell population growth influenced by radiation treatment. We model how the body biologically receives a physically delivered dose of radiation to the affected tumorous area in the form of a generalized LQ model, modified to account for the conversion process of sublethal lesions into lethal lesions at high radiation doses. We obtain good agreement between our clinical data and our numerical simulations of brain cancer progression given by the mathematical model, which couples tumor growth dynamics and the effect of irradiation. The correlation, spanning a wide dataset, demonstrates the potential of the mathematical model to describe the dynamics of brain tumor growth influenced by radiotherapy.

Neuropeptides, Microbiota, and Behavior.

PubMed

Holzer, P

2016-01-01

The gut microbiota and the brain interact with each other through multiple bidirectional signaling pathways in which neuropeptides and neuroactive peptide messengers play potentially important mediator roles. Currently, six particular modes of a neuropeptide link are emerging. (i) Neuropeptides and neurotransmitters contribute to the mutual microbiota-host interaction. (ii) The synthesis of neuroactive peptides is influenced by microbial control of the availability of amino acids. (iii) The activity of neuropeptides is tempered by microbiota-dependent autoantibodies. (iv) Peptide signaling between periphery and brain is modified by a regulatory action of the gut microbiota on the blood-brain barrier. (v) Within the brain, gut hormones released under the influence of the gut microbiota turn into neuropeptides that regulate multiple aspects of brain activity. (vi) Cerebral neuropeptides participate in the molecular, behavioral, and autonomic alterations which the brain undergoes in response to signals from the gut microbiota. © 2016 Elsevier Inc. All rights reserved.

Voxel-Based Morphometry and fMRI Revealed Differences in Brain Gray Matter in Breastfed and Milk Formula-Fed Children.

PubMed

Ou, X; Andres, A; Pivik, R T; Cleves, M A; Snow, J H; Ding, Z; Badger, T M

2016-04-01

Infant diets may have significant impact on brain development in children. The aim of this study was to evaluate brain gray matter structure and function in 8-year-old children who were predominantly breastfed or fed cow's milk formula as infants. Forty-two healthy children (breastfed: n = 22, 10 boys and 12 girls; cow's milk formula: n = 20, 10 boys and 10 girls) were studied by using structural MR imaging (3D T1-weighted imaging) and blood oxygen level-dependent fMRI (while performing tasks involving visual perception and language functions). They were also administered standardized tests evaluating intelligence (Reynolds Intellectual Assessment Scales) and language skills (Clinical Evaluation of Language Fundamentals). Total brain gray matter volume did not differ between the breastfed and cow's milk formula groups. However, breastfed children had significantly higher (P < .05, corrected) regional gray matter volume measured by voxel-based morphometry in the left inferior temporal lobe and left superior parietal lobe compared with cow's milk formula-fed children. Breastfed children showed significantly more brain activation in the right frontal and left/right temporal lobes on fMRI when processing the perception task and in the left temporal/occipital lobe when processing the visual language task than cow's milk formula-fed children. The imaging findings were associated with significantly better performance for breastfed than cow's milk formula-fed children on both tasks. Our findings indicated greater regional gray matter development and better regional gray matter function in breastfed than cow's milk formula-fed children at 8 years of age and suggested that infant diets may have long-term influences on brain development in children. © 2016 by American Journal of Neuroradiology.

Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

PubMed

Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

2017-02-01

It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

PubMed

Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

2017-01-01

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Biological etiologies of transsexualism].

PubMed

Butty, Anne-Virginie; Bianchi-Demicheli, Francesco

2016-03-16

Transsexualism or gender dysphoria is a disorder of sexual identity of unknown etiology. At the biological level, one assumes atypical brain development during certain periods of its formation (genesis) notably during embryogenesis, as a result of altered hormonal influence and a particular genetic polymorphism. This article summarizes the research conducted to date in these three areas only, excluding psycho-social and environmental factors.

BRAIN MECHANISMS AND INTELLIGENCE, A QUANTITATIVE STUDY OF INJURIES TO THE BRAIN.

ERIC Educational Resources Information Center

LASHLEY, K.S.

SEVERAL EXPERIMENTS WITH RATS INVOLVING THE INFLUENCE OF CEREBRAL DESTRUCTION ON LEARNING ABILITY ARE DESCRIBED. THE TWO MAJOR EXPERIMENTS STUDY THE RETENTION OF THE MAZE HABIT AFTER CEREBRAL LESIONS AND THE INFLUENCE OF CEREBRAL LESIONS ON THE CAPACITY TO LEARN (INITIAL FORMATION OF HABITS). THEORECTICAL ANALYSIS OF THE LEARNING (BEHAVIOR)…

Premature brain aging in humans exposed to maternal nutrient restriction during early gestation.

PubMed

Franke, Katja; Gaser, Christian; Roseboom, Tessa J; Schwab, Matthias; de Rooij, Susanne R

2018-06-01

Prenatal exposure to undernutrition is widespread in both developing and industrialized countries, causing irreversible damage to the developing brain, resulting in altered brain structure and decreased cognitive function during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now enabling studies of the effects of prenatal undernutrition during gestation on brain aging in late adulthood. We hypothesized that study participants prenatally exposed to maternal nutrient restriction (MNR) would demonstrate altered brain structure resembling premature brain aging in late adulthood, expecting the effect being stronger in men. Utilizing the Dutch famine birth cohort (n = 118; mean age: 67.5 ± 0.9 years), this study implements an innovative biomarker for individual brain aging, using structural neuroimaging. BrainAGE was calculated using state-of-the-art pattern recognition methods, trained on an independent healthy reference sample, then applied to the Dutch famine MRI sample, to evaluate the effects of prenatal undernutrition during early gestation on individual brain aging in late adulthood. Exposure to famine in early gestation was associated with BrainAGE scores indicative of an older-appearing brain in the male sample (mean difference to subjects born before famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in individual BrainAGE scores in the male sample, maternal age at birth, head circumference at birth, medical treatment of hypertension, history of cerebral incidences, actual heart rate, and current alcohol intake emerged to be the most influential variables (adjusted R 2  = 0.63, p < 0.01). The findings of our study on exposure to prenatal undernutrition being associated with a status of premature brain aging during late adulthood, as well as individual brain structure being shaped by birth- and late-life health characteristics, are strongly supporting the critical importance of sufficient nutrient supply during pregnancy. Interestingly, the status of premature brain aging in participants exposed to the Dutch famine during early gestation occurred in the absence of fetal growth restriction at birth as well as vascular pathology in late-life. Additionally, the neuroimaging brain aging biomarker presented in this study will further enable tracking effects of environmental influences or (preventive) treatments on individual brain maturation and aging in epidemiological and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

PubMed

Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

2017-12-01

Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

Study of heart-brain interactions through EEG, ECG, and emotions

NASA Astrophysics Data System (ADS)

Ramasamy, Mouli; Varadan, Vijay K.

2017-04-01

Neurocardiology is the exploration of neurophysiological, neurological and neuroanatomical facets of neuroscience's influence in cardiology. The paraphernalia of emotions on the heart and brain are premeditated because of the interaction between the central and peripheral nervous system. This is an investigative attempt to study emotion based neurocardiology and the factors that influence this phenomenon. The factors include: interaction between sleep EEG (electroencephalogram) and ECG (electrocardiogram), relationship between emotion and music, psychophysiological coherence between the heart and brain, emotion recognition techniques, and biofeedback mechanisms. Emotions contribute vitally to the mundane life and are quintessential to a numerous biological and everyday-functional modality of a human being. Emotions are best represented through EEG signals, and to a certain extent, can be observed through ECG and body temperature. Confluence of medical and engineering science has enabled the monitoring and discrimination of emotions influenced by happiness, anxiety, distress, excitement and several other factors that influence the thinking patterns and the electrical activity of the brain. Similarly, HRV (Heart Rate Variability) widely investigated for its provision and discerning characteristics towards EEG and the perception in neurocardiology.

Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

PubMed

Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

2015-08-01

There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of prenatal maternal stress on serotonin and fetal development.

PubMed

St-Pierre, Joey; Laurent, Laetitia; King, Suzanne; Vaillancourt, Cathy

2016-12-01

Fetuses are exposed to many environmental perturbations that can influence their development. These factors can be easily identifiable such as drugs, chronic diseases or prenatal maternal stress. Recently, it has been demonstrated that the serotonin synthetized by the placenta was crucial for fetal brain development. Moreover, many studies show the involvement of serotonin system alteration in psychiatric disease during childhood and adulthood. This review summarizes existing studies showing that prenatal maternal stress, which induces alteration of serotonin systems (placenta and fetal brain) during a critical window of early development, could lead to alteration of fetal development and increase risks of psychiatric diseases later in life. This phenomenon, termed fetal programming, could be moderated by the sex of the fetus. This review highlights the need to better understand the modification of the maternal, placental and fetal serotonin systems induced by prenatal maternal stress in order to find early biomarkers of psychiatric disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

PubMed Central

Xiong, Fuxia; Zhang, Lubo

2012-01-01

Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

NEURONAL ACTION ON THE DEVELOPING BLOOD VESSEL PATTERN

PubMed Central

James, Jennifer M.; Mukouyama, Yoh-suke

2011-01-01

The nervous system relies on a highly specialized network of blood vessels for development and neuronal survival. Recent evidence suggests that both the central and peripheral nervous systems (CNS and PNS) employ multiple mechanisms to shape the vascular tree to meet its specific metabolic demands, such as promoting nerve-artery alignment in the PNS or the development the blood brain barrier in the CNS. In this article we discuss how the nervous system directly influences blood vessel patterning resulting in neuro-vascular congruence that is maintained throughout development and in the adult. PMID:21978864

Nose-to-brain peptide delivery - The potential of nanotechnology.

PubMed

Samaridou, Eleni; Alonso, Maria José

2018-06-01

Nose-to-brain (N-to-B) delivery offers to protein and peptide drugs the possibility to reach the brain in a non-invasive way. This article is a comprehensive review of the state-of-the-art of this emerging peptide delivery route, as well as of the challenges associated to it. Emphasis is given on the potential of nanosized drug delivery carriers to enhance the direct N-to-B transport of protein or peptide drugs. In particular, polymer- and lipid- based nanocarriers are comparatively analyzed in terms of the influence of their physicochemical characteristics and composition on their in vivo fate and efficacy. The use of biorecognitive ligands and permeation enhancers in order to enhance their brain targeting efficiency is also discussed. The article concludes highlighting the early stage of this research field and its still unveiled potential. The final message is that more explicatory PK/PD studies are required in order to achieve the translation from preclinical to the clinical development phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

3. Neural changes in different gravity and ecophysiological environments - A survey

NASA Astrophysics Data System (ADS)

Slenzka, K.

Neural changes or neuronal plasticity occur after and during different stimulations and inputs in general. Gravity is one major input to the brain transferred from the vestibular system. However, often also direct effects of gravity on the cellular level are discussed. Our group was investigating the influence of different gravity environments on a large variety of neuronal enzymes in the developing fish brain. Long-term space travel or bases on Moon and Mars will have to deal not only with neural changes based on the different gravity environment, but also with potential negative or even toxic changes in the respective life support system. Our goal is now to identify reported enzyme activity changes in the brain based for example on potential toxic drugs or endocrine disruptors in combination with gravity induced changes. In this paper a survey will be undertaken discussing recent results obtained in ecotoxicology, gravitational biology combined with new data from our group regarding potential differences in brain glucose-6-phosphate dehydrogenase of medaka and zebrafish.

Soldier Health Habits and the Metabolically Optimized Brain.

PubMed

Friedl, Karl E; Breivik, Torbjorn J; Carter, Robert; Leyk, Dieter; Opstad, Per Kristian; Taverniers, John; Trousselard, Marion

2016-11-01

Human performance enhancement was the subject of a NATO workshop that considered the direct benefits of individual soldier health and fitness habits to brain health and performance. Some of the important health and fitness include physical activity and purposeful exercise, nutritional intake, sleep and rest behaviors, psychological outlook and mindfulness, and other physiologically based systemic challenges such as thermal exposure. These influences were considered in an integrated framework with insights contributed by each of five participating NATO member countries using representative research to highlight relevant interrelationships. Key conclusions are that (1) understanding the neurobiological bases and consequences of personal health behaviors is a priority for soldier performance research, and this also involves long-term brain health consequences to veterans and (2) health and fitness habits have been underappreciated as reliably effective performance enhancers and these should be preferred targets in the development of scientifically based recommendations for soldier brain health and performance. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota.

PubMed

Bauer, Paige V; Hamr, Sophie C; Duca, Frank A

2016-02-01

Despite significant progress in understanding the homeostatic regulation of energy balance, successful therapeutic options for curbing obesity remain elusive. One potential target for the treatment of obesity is via manipulation of the gut-brain axis, a complex bidirectional communication system that is crucial in maintaining energy homeostasis. Indeed, ingested nutrients induce secretion of gut peptides that act either via paracrine signaling through vagal and non-vagal neuronal relays, or in an endocrine fashion via entry into circulation, to ultimately signal to the central nervous system where appropriate responses are generated. We review here the current hypotheses of nutrient sensing mechanisms of enteroendocrine cells, including the release of gut peptides, mainly cholecystokinin, glucagon-like peptide-1, and peptide YY, and subsequent gut-to-brain signaling pathways promoting a reduction of food intake and an increase in energy expenditure. Furthermore, this review highlights recent research suggesting this energy regulating gut-brain axis can be influenced by gut microbiota, potentially contributing to the development of obesity.

Creative thinking as orchestrated by semantic processing vs. cognitive control brain networks.

PubMed

Abraham, Anna

2014-01-01

Creativity is primarily investigated within the neuroscientific perspective as a unitary construct. While such an approach is beneficial when trying to infer the general picture regarding creativity and brain function, it is insufficient if the objective is to uncover the information processing brain mechanisms by which creativity occurs. As creative thinking emerges through the dynamic interplay between several cognitive processes, assessing the neural correlates of these operations would enable the development and characterization of an information processing framework from which to better understand this complex ability. This article focuses on two aspects of creative cognition that are central to generating original ideas. "Conceptual expansion" refers to the ability to widen one's conceptual structures to include unusual or novel associations, while "overcoming knowledge constraints" refers to our ability to override the constraining influence imposed by salient or pertinent knowledge when trying to be creative. Neuroimaging and neuropsychological evidence is presented to illustrate how semantic processing and cognitive control networks in the brain differentially modulate these critical facets of creative cognition.

DISC1 genetics, biology and psychiatric illness

PubMed Central

THOMSON, Pippa A.; MALAVASI, Elise L.V.; GRÜNEWALD, Ellen; SOARES, Dinesh C.; BORKOWSKA, Malgorzata; MILLAR, J. Kirsty

2012-01-01

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain. PMID:23550053

Experience-Dependent Neural Plasticity in the Adult Damaged Brain

ERIC Educational Resources Information Center

Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

2011-01-01

Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).

PubMed

Rektor, Ivan; Schachter, Steven C; Arzy, Shahar; Baloyannis, Stavros J; Bazil, Carl; Brázdil, Milan; Engel, Jerome; Helmstaedter, Gerhard; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kesner, Ladislav; Komárek, Vladimír; Krämer, Günter; Leppik, Ilo E; Mann, Michael W; Mula, Marco; Risse, Gail L; Stoker, Guy W; Kasteleijn-Nolst Trenité, Dorothée G A; Trimble, Michael; Tyrliková, Ivana; Korczyn, Amos D

2013-08-01

Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art. Copyright © 2013. Published by Elsevier Inc.

Altered brain activity for phonological manipulation in dyslexic Japanese children.

PubMed

Kita, Yosuke; Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi

2013-12-01

Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.

Deep brain stimulation for psychiatric disorders: where we are now.

PubMed

Cleary, Daniel R; Ozpinar, Alp; Raslan, Ahmed M; Ko, Andrew L

2015-06-01

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Altered brain activity for phonological manipulation in dyslexic Japanese children

PubMed Central

Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi

2013-01-01

Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children. PMID:24052613

The effects of handwriting experience on functional brain development in pre-literate children

PubMed Central

James, Karin H.; Engelhardt, Laura

2014-01-01

In an age of increasing technology, the possibility that typing on a keyboard will replace handwriting raises questions about the future usefulness of handwriting skills. Here we present evidence that brain activation during letter perception is influenced in different, important ways by previous handwriting of letters versus previous typing or tracing of those same letters. Preliterate, five-year old children printed, typed, or traced letters and shapes, then were shown images of these stimuli while undergoing functional MRI scanning. A previously documented “reading circuit” was recruited during letter perception only after handwriting—not after typing or tracing experience. These findings demonstrate that handwriting is important for the early recruitment in letter processing of brain regions known to underlie successful reading. Handwriting therefore may facilitate reading acquisition in young children. PMID:25541600

Neural responses to macronutrients: hedonic and homeostatic mechanisms.

PubMed

Tulloch, Alastair J; Murray, Susan; Vaicekonyte, Regina; Avena, Nicole M

2015-05-01

The brain responds to macronutrients via intricate mechanisms. We review how the brain's neural systems implicated in homeostatic control of feeding and hedonic responses are influenced by the ingestion of specific types of food. We discuss how these neural systems are dysregulated in preclinical models of obesity. Findings from these studies can increase our understanding of overeating and, perhaps in some cases, the development of obesity. In addition, a greater understanding of the neural circuits affected by the consumption of specific macronutrients, and by obesity, might lead to new treatments and strategies for preventing unhealthy weight gain. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

PubMed

Ohta, Ken-Ichi; Suzuki, Shingo; Warita, Katsuhiko; Kaji, Tomohiro; Kusaka, Takashi; Miki, Takanori

2017-04-01

Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood. © 2017 International Society for Neurochemistry.

Genetic and environmental factors interact to influence anxiety.

PubMed

Gross, Cornelius; Hen, René

2004-01-01

Both genetic and environmental factors influence normal anxiety traits as well as anxiety disorders. In addition it is becoming increasingly clear that these factors interact to produce specific anxiety-related behaviors. For example, in humans and in monkeys mutations in the gene encoding for the serotonin transporter result in increased anxiety in adult life when combined with a stressful environment during development. Another recent example comes from twin studies suggesting that a small hippocampus can be a predisposing condition that renders individuals susceptible to post traumatic stress disorder. Such examples illustrate how specific mutations leading to abnormal brain development may increase vulnerability to environmental insults which may in turn lead to specific anxiety disorders.

Brain Substrates of Recovery from Misleading Influence

PubMed Central

Dudai, Yadin; Dolan, Raymond J.; Sharot, Tali

2014-01-01

Humans are strongly influenced by their environment, a dependence that can lead to errors in judgment. Although a rich literature describes how people are influenced by others, little is known regarding the factors that predict subsequent rectification of misleading influence. Using a mediation model in combination with brain imaging, we propose a model for the correction of misinformation. Specifically, our data suggest that amygdala modulation of hippocampal mnemonic representations, during the time of misleading social influence, is associated with reduced subsequent anterior–lateral prefrontal cortex activity that reflects correction. These findings illuminate the process by which erroneous beliefs are, or fail to be, rectified and highlight how past influence constrains subsequent correction. PMID:24899698

Epigenetic Age Acceleration Assessed with Human White-Matter Images.

PubMed

Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

2017-05-03

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age, relative to chronological age. The white matter tracts within the brain are also highly sensitive to aging processes. We show that increased biological aging (measured using epigenetic data from blood samples) is correlated with reduced integrity of white matter tracts within the human brain (measured using diffusion tensor imaging) with data from a large sample of Mexican-American families. Given the family design of the sample, we are also able to demonstrate that epigenetic aging and white matter tract integrity also share common genetic influences. Therefore, epigenetic age may be a potential, and accessible, biomarker of brain aging. Copyright © 2017 the authors 0270-6474/17/374735-09$15.00/0.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide☆☆☆★

PubMed Central

Thompson, Paul M.; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Bearden, Carrie E.; Boedhoe, Premika S.; Brouwer, Rachel M.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cannon, Dara M.; Cohen, Ronald A.; Conrod, Patricia J.; Dale, Anders M.; Deary, Ian J.; Dennis, Emily L.; de Reus, Marcel A.; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E.; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C.; Grabe, Hans J.; Guadalupe, Tulio; Gutman, Boris A.; Hashimoto, Ryota; Hibar, Derrek P.; Holland, Dominic; Hoogman, Martine; Pol, Hilleke E. Hulshoff; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S.; Lee, Phil H.; Mackey, Scott; Martin, Nicholas G.; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E.; Morey, Rajendra A.; Nichols, Thomas E.; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M.; Smit, Dirk J.A.; Smoller, Jordan W.; Stein, Dan J.; Stein, Jason L.; Toro, Roberto; Turner, Jessica A.; van den Heuvel, Martijn P.; van den Heuvel, Odile L.; van Erp, Theo G.M.; van Rooij, Daan; Veltman, Dick J.; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M.; Whelan, Christopher D.; Wright, Margaret J.; Ye, Jieping

2016-01-01

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens – now numbering over 30,000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far. PMID:26658930

Towards child versus adult brain mechanical properties.

PubMed

Chatelin, S; Vappou, J; Roth, S; Raul, J S; Willinger, R

2012-02-01

The characterization of brain tissue mechanical properties is of crucial importance in the development of realistic numerical models of the human head. While the mechanical behavior of the adult brain has been extensively investigated in several studies, there is a considerable paucity of data concerning the influence of age on mechanical properties of the brain. Therefore, the implementation of child and infant head models often involves restrictive assumptions like properties scaling from adult or animal data. The present study presents a step towards the investigation of the effects of age on viscoelastic properties of human brain tissue from a first set of dynamic oscillatory shear experiments. Tests were also performed on three different locations of brain (corona radiata, thalamus and brainstem) in order to investigate regional differences. Despite the limited number of child brain samples a significant increase in both storage and loss moduli occurring between the age of 5 months and the age of 22 months was found, confirmed by statistical Student's t-tests (p=0.104,0.038 and 0.054 for respectively corona radiata, thalamus and brain stem samples locations respectively). The adult brain appears to be 3-4 times stiffer than the young child one. Moreover, the brainstem was found to be approximately 2-3 times stiffer than both gray and white matter from corona radiata and thalamus. As a tentative conclusion, this study provides the first rheological data on the human brain at different ages and brain regions. This data could be implemented in numerical models of the human head, especially in models concerning pediatric population. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rearing environment influences boldness and prey acquisition behavior, and brain and lens development of bull trout

USGS Publications Warehouse

Brignon, William R.; Pike, Martin M.; Ebbesson, Lars O.E.; Schaller, Howard A.; Peterson, James T.; Schreck, Carl B.

2018-01-01

Animals reared in barren captive environments exhibit different developmental trajectories and behaviors than wild counterparts. Hence, the captive phenotypes may influence the success of reintroduction and recovery programs for threatened and endangered species. We collected wild bull trout embryos from the Metolius River Basin, Oregon and reared them in differing environments to better understand how captivity affects the bull trout Salvelinus confluentusphenotype. We compared the boldness and prey acquisition behaviors and development of the brain and eye lens of bull trout reared in conventional barren and more structurally complex captive environments with that of wild fish. Wild fish and captive reared fish from complex habitats exhibited a greater level of boldness and prey acquisition ability, than fish reared in conventional captive environments. In addition, the eye lens of conventionally reared bull trout was larger than complex reared captive fish or same age wild fish. Interestingly, we detected wild fish had a smaller relative cerebellum than either captive reared treatment. Our results suggest that rearing fish in more complex captive environments can create a more wild-like phenotype than conventional rearing practices. A better understanding of the effects of captivity on the development and behavior of bull trout can inform rearing and reintroduction programs though prediction of the performance of released individuals.

Estimated maximal and current brain volume predict cognitive ability in old age.

PubMed

Royle, Natalie A; Booth, Tom; Valdés Hernández, Maria C; Penke, Lars; Murray, Catherine; Gow, Alan J; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

2013-12-01

Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging. Copyright © 2013 Elsevier Inc. All rights reserved.

Prenatal testosterone and gender-related behaviour.

PubMed

Hines, Melissa

2006-11-01

Testosterone plays an important role in mammalian brain development. In neural regions with appropriate receptors testosterone, or its metabolites, influences patterns of cell death and survival, neural connectivity and neurochemical characterization. Consequently, testosterone exposure during critical periods of early development produces permanent behavioural changes. In humans, affected behaviours include childhood play behaviour, sexual orientation, core gender identity and other characteristics that show sex differences (i.e. differ on average between males and females). These influences have been demonstrated primarily in individuals who experienced marked prenatal hormone abnormalities and associated ambiguities of genital development (e.g. congenital adrenal hyperplasia). However, there is also evidence that testosterone works within the normal range to make some individuals within each sex more sex-typical than others. The size of testosterone-related influences, and perhaps even their existence, varies from one sex-typed characteristic to another. For instance: prenatal exposure to high levels of testosterone has a substantial influence on sex-typical play behaviour, including sex-typed toy preferences, whereas influences on core gender identify and sexual orientation are less dramatic. In addition: there appears to be little or no influence of prenatal testosterone on mental rotations ability, although mental rotations ability shows a marked sex difference. These findings have implications for basic understanding of the role of testosterone in normative gender development, as well as for the clinical management of individuals with disorders of sex development (formerly called intersex syndromes).

Fat brains, greedy genes, and parent power: a biobehavioural risk model of child and adult obesity.

PubMed

Carnell, Susan; Kim, Yale; Pryor, Katherine

2012-06-01

We live in a world replete with opportunities to overeat highly calorific, palatable foods - yet not everyone becomes obese. Why? We propose that individuals show differences in appetitive traits (e.g. food cue responsiveness, satiety sensitivity) that manifest early in life and predict their eating behaviours and weight trajectories. What determines these traits? Parental feeding restriction is associated with higher child adiposity, pressure to eat with lower adiposity, and both strategies with less healthy eating behaviours, while authoritative feeding styles coincide with more positive outcomes. But, on the whole, twin and family studies argue that nature has a greater influence than nurture on adiposity and eating behaviour, and behavioural investigations of genetic variants that are robustly associated with obesity (e.g. FTO) confirm that genes influence appetite. Meanwhile, a growing body of neuroimaging studies in adults, children and high risk populations suggests that structural and functional variation in brain networks associated with reward, emotion and control might also predict appetite and obesity, and show genetic influence. Together these different strands of evidence support a biobehavioural risk model of obesity development. Parental feeding recommendations should therefore acknowledge the powerful - but modifiable - contribution of genetic and neurological influences to children's eating behaviour.

Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.

PubMed

Kochunov, Peter; Ganjgahi, Habib; Winkler, Anderson; Kelly, Sinead; Shukla, Dinesh K; Du, Xiaoming; Jahanshad, Neda; Rowland, Laura; Sampath, Hemalatha; Patel, Binish; O'Donnell, Patricio; Xie, Zhiyong; Paciga, Sara A; Schubert, Christian R; Chen, Jian; Zhang, Guohao; Thompson, Paul M; Nichols, Thomas E; Hong, L Elliot

2016-12-01

Altered brain connectivity is implicated in the development and clinical burden of schizophrenia. Relative to matched controls, schizophrenia patients show (1) a global and regional reduction in the integrity of the brain's white matter (WM), assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA), and (2) accelerated age-related decline in FA values. In the largest mega-analysis to date, we tested if differences in the trajectories of WM tract development influenced patient-control differences in FA. We also assessed if specific tracts showed exacerbated decline with aging. Three cohorts of schizophrenia patients (total n = 177) and controls (total n = 249; age = 18-61 years) were ascertained with three 3T Siemens MRI scanners. Whole-brain and regional FA values were extracted using ENIGMA-DTI protocols. Statistics were evaluated using mega- and meta-analyses to detect effects of diagnosis and age-by-diagnosis interactions. In mega-analysis of whole-brain averaged FA, schizophrenia patients had lower FA (P = 10 -11 ) and faster age-related decline in FA (P = 0.02) compared with controls. Tract-specific heterochronicity measures, that is, abnormal rates of adolescent maturation and aging explained approximately 50% of the regional variance effects of diagnosis and age-by-diagnosis interaction in patients. Interactive, three-dimensional visualization of the results is available at www.enigma-viewer.org. WM tracts that mature later in life appeared more sensitive to the pathophysiology of schizophrenia and were more susceptible to faster age-related decline in FA values. Hum Brain Mapp 37:4673-4688, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cerebellar Growth Impairment Characterizes School-Aged Children Born Preterm without Perinatal Brain Lesions.

PubMed

Pieterman, K; White, T J; van den Bosch, G E; Niessen, W J; Reiss, I K M; Tibboel, D; Hoebeek, F E; Dudink, J

2018-05-01

Infants born preterm are commonly diagnosed with structural brain lesions known to affect long-term neurodevelopment negatively. Yet, the effects of preterm birth on brain development in the absence of intracranial lesions remain to be studied in detail. In this study, we aim to quantify long term consequences of preterm birth on brain development in this specific group. Neonatal cranial sonography and follow-up T1-weighted MR imaging and DTI were performed to evaluate whether the anatomic characteristics of the cerebrum and cerebellum in a cohort of school-aged children (6-12 years of age) were related to gestational age at birth in children free of brain lesions in the perinatal period. In the cohort consisting of 36 preterm (28-37 weeks' gestational age) and 66 term-born infants, T1-weighted MR imaging and DTI at 6-12 years revealed a reduction of cerebellar white matter volume (β = 0.387, P < .001), altered fractional anisotropy of cerebellar white matter (β = -0.236, P = .02), and a reduction of cerebellar gray and white matter surface area (β = 0.337, P < .001; β = 0.375, P < .001, respectively) in relation to birth age. Such relations were not observed for the cerebral cortex or white matter volume, surface area, or diffusion quantities. The results of our study show that perinatal influences that are not primarily neurologic are still able to disturb long-term neurodevelopment, particularly of the developing cerebellum. Including the cerebellum in future neuroprotective strategies seems therefore essential. © 2018 by American Journal of Neuroradiology.