Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

NASA Astrophysics Data System (ADS)

Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

2011-03-01

The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

PubMed

El-Akabawy, Gehan; El-Kholy, Wael

2014-05-01

Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. Copyright © 2014 Elsevier GmbH. All rights reserved.

Exploring Deep Space - Uncovering the Anatomy of Periventricular Structures to Reveal the Lateral Ventricles of the Human Brain.

PubMed

Colibaba, Alexandru S; Calma, Aicee Dawn B; Webb, Alexandra L; Valter, Krisztina

2017-10-22

Anatomy students are typically provided with two-dimensional (2D) sections and images when studying cerebral ventricular anatomy and students find this challenging. Because the ventricles are negative spaces located deep within the brain, the only way to understand their anatomy is by appreciating their boundaries formed by related structures. Looking at a 2D representation of these spaces, in any of the cardinal planes, will not enable visualisation of all of the structures that form the boundaries of the ventricles. Thus, using 2D sections alone requires students to compute their own mental image of the 3D ventricular spaces. The aim of this study was to develop a reproducible method for dissecting the human brain to create an educational resource to enhance student understanding of the intricate relationships between the ventricles and periventricular structures. To achieve this, we created a video resource that features a step-by-step guide using a fiber dissection method to reveal the lateral and third ventricles together with the closely related limbic system and basal ganglia structures. One of the advantages of this method is that it enables delineation of the white matter tracts that are difficult to distinguish using other dissection techniques. This video is accompanied by a written protocol that provides a systematic description of the process to aid in the reproduction of the brain dissection. This package offers a valuable anatomy teaching resource for educators and students alike. By following these instructions educators can create teaching resources and students can be guided to produce their own brain dissection as a hands-on practical activity. We recommend that this video guide be incorporated into neuroanatomy teaching to enhance student understanding of the morphology and clinical relevance of the ventricles.

Extracting the inclination angle of nerve fibers within the human brain with 3D-PLI independent of system properties

NASA Astrophysics Data System (ADS)

Reckfort, Julia; Wiese, Hendrik; Dohmen, Melanie; Grässel, David; Pietrzyk, Uwe; Zilles, Karl; Amunts, Katrin; Axer, Markus

2013-09-01

The neuroimaging technique 3D-polarized light imaging (3D-PLI) has opened up new avenues to study the complex nerve fiber architecture of the human brain at sub-millimeter spatial resolution. This polarimetry technique is applicable to histological sections of postmortem brains utilizing the birefringence of nerve fibers caused by the regular arrangement of lipids and proteins in the myelin sheaths surrounding axons. 3D-PLI provides a three-dimensional description of the anatomical wiring scheme defined by the in-section direction angle and the out-of-section inclination angle. To date, 3D-PLI is the only available method that allows bridging the microscopic and the macroscopic description of the fiber architecture of the human brain. Here we introduce a new approach to retrieve the inclination angle of the fibers independently of the properties of the used polarimeters. This is relevant because the image resolution and the signal transmission inuence the measured birefringent signal (retardation) significantly. The image resolution was determined using the USAF- 1951 testchart applying the Rayleigh criterion. The signal transmission was measured by elliptical polarizers applying the Michelson contrast and histological slices of the optic tract of a postmortem brain. Based on these results, a modified retardation-inclination transfer function was proposed to extract the fiber inclination. The comparison of the actual and the inclination angles calculated with the theoretically proposed and the modified transfer function revealed a significant improvement in the extraction of the fiber inclinations.

Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: a stereological experiment.

PubMed

Whitney, Elizabeth R; Kemper, Thomas L; Rosene, Douglas L; Bauman, Margaret L; Blatt, Gene J

2008-02-15

In a study of human Purkinje cell (PC) number, a striking mismatch between the number of PCs observed with the Nissl stain and the number of PCs immunopositive for calbindin-D28k (CB) was identified in 2 of the 10 brains examined. In the remaining eight brains this mismatch was not observed. Further, in these eight brains, analysis of CB immunostained sections counterstained with the Nissl stain revealed that more than 99% Nissl stained PCs were also immunopositive for CB. In contrast, in the two discordant brains, only 10-20% of CB immunopositive PCs were also identified with the Nissl stain. Although this finding was unexpected, a historical survey of the literature revealed that Spielmeyer [Spielmeyer W. Histopathologie des nervensystems. Julius Springer: Berlin; 1922. p. 56-79] described human cases with PCs that lacked the expected Nissl staining intensity, an important historical finding and critical issue when studying postmortem human brains. The reason for this failure in Nissl staining is not entirely clear, but it may result from premortem circumstances since it is not accounted for by postmortem delay or processing variables. Regardless of the exact cause, these observations suggest that Nissl staining may not be a reliable marker for PCs and that CB is an excellent alternative marker.

CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.

PubMed

Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L; Precht, Patricia; Mughal, Mohamed R; Wood, William H; Zhang, Yonqing; Becker, Kevin G; Mattson, Mark P; Pazin, Michael J

2011-01-01

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease.

CHD5, a Brain-Specific Paralog of Mi2 Chromatin Remodeling Enzymes, Regulates Expression of Neuronal Genes

PubMed Central

Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L.; Precht, Patricia; Mughal, Mohamed R.; Wood, William H.; Zhang, Yonqing; Becker, Kevin G.; Mattson, Mark P.; Pazin, Michael J.

2011-01-01

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease. PMID:21931736

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: Development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

NASA Astrophysics Data System (ADS)

Peng, Yu-Hao; Heintz, Ryan; Wang, Zhuo; Guo, Yumei; Myers, Kalisa; Scremin, Oscar; Maarek, Jean-Michel; Holschneider, Daniel

2014-12-01

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex--changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies.

Human brain factor 1, a new member of the fork head gene family

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

Murphy, D.B.; Wiese, S.; Burfeind, P.

1994-06-01

Analysis of cDNA clones that cross-hybridized with the fork head domain of the rat HNF-3 gene family revealed 10 cDNAs from human fetal brain and human testis cDNA libraries containing this highly conserved DNA-binding domain. Three of these cDNAs (HFK1, HFK2, and HFK3) were further analyzed. The cDNA HFK1 has a length of 2557 nucleotides and shows strong homology at the nucleotide level (91.2%) to brain factor 1 (BF-1) from rat. The HFK1 cDNA codes for a putative 476 amino acid protein. The homology to BF-1 from rat in the coding region at the amino acid level is 87.5%. Themore » fork head homologous region includes 111 amino acids starting at amino acid 160 and has a 97.5% homology to BF-1. Southern hybridization revealed that HFK1 is highly conserved among mammalian species and possibly birds. Northern analysis with total RNA from human tissues and poly(A)-rich RNA from mouse revealed a 3.2-kb transcript that is present in human and mouse fetal brain and in adult mouse brain. In situ hybridization with sections of mouse embryo and human fetal brain reveals that HFK1 expression is restricted to the neuronal cells in the telencepthalon, with strong expression being observed in the developing dentate gyrus and hippocampus. HFK1 was chromosomally localized by in situ hybridization to 14q12. The cDNA clones HFK2 and HFK3 were analyzed by restriction analysis and sequencing. HFK2 and HFK3 were found to be closely related but different from HFK1. Therefore, it would appear that HFK1, HFK2, HFK3, and BF-1 form a new fork head related subfamily. 33 refs., 6 figs.« less

FTIR Imaging of Brain Tissue Reveals Crystalline Creatine Deposits Are an ex Vivo Marker of Localized Ischemia during Murine Cerebral Malaria: General Implications for Disease Neurochemistry

PubMed Central

2012-01-01

Phosphocreatine is a major cellular source of high energy phosphates, which is crucial to maintain cell viability under conditions of impaired metabolic states, such as decreased oxygen and energy availability (i.e., ischemia). Many methods exist for the bulk analysis of phosphocreatine and its dephosphorylated product creatine; however, no method exists to image the distribution of creatine or phosphocreatine at the cellular level. In this study, Fourier transform infrared (FTIR) spectroscopic imaging has revealed the ex vivo development of creatine microdeposits in situ in the brain region most affected by the disease, the cerebellum of cerebral malaria (CM) diseased mice; however, such deposits were also observed at significantly lower levels in the brains of control mice and mice with severe malaria. In addition, the number of deposits was observed to increase in a time-dependent manner during dehydration post tissue cutting. This challenges the hypotheses in recent reports of FTIR spectroscopic imaging where creatine microdeposits found in situ within thin sections from epileptic, Alzheimer’s (AD), and amlyoid lateral sclerosis (ALS) diseased brains were proposed to be disease specific markers and/or postulated to contribute to the brain pathogenesis. As such, a detailed investigation was undertaken, which has established that the creatine microdeposits exist as the highly soluble HCl salt or zwitterion and are an ex-vivo tissue processing artifact and, hence, have no effect on disease pathogenesis. They occur as a result of creatine crystallization during dehydration (i.e., air-drying) of thin sections of brain tissue. As ischemia and decreased aerobic (oxidative metabolism) are common to many brain disorders, regions of elevated creatine-to-phosphocreatine ratio are likely to promote crystal formation during tissue dehydration (due to the lower water solubility of creatine relative to phosphocreatine). The results of this study have demonstrated that although the deposits do not occur in vivo, and do not directly play any role in disease pathogenesis, increased levels of creatine deposits within air-dried tissue sections serve as a highly valuable marker for the identification of tissue regions with an altered metabolic status. In this study, the location of crystalline creatine deposits were used to identify whether an altered metabolic state exists within the molecular and granular layers of the cerebellum during CM, which complements the recent discovery of decreased oxygen availability in the brain during this disease. PMID:23259037

O-GlcNAc modification of radial glial vimentin filaments in the developing chick brain.

PubMed

Farach, Andrew M; Galileo, Deni S

2008-12-01

We examined the post-translational modification of intracellular proteins by beta-O-linked N-acetylglucosamine (O-GlcNAc) with regard to neurofilament phosphorylation in the developing chick optic tectum. A regulated developmental pattern of O-GlcNAcylation was discovered in the developing brain. Most notably, discernible staining occurs along radial glial filaments but not along neuronal filaments in vivo. Immunohistochemical analyses in sections of progressive stages of development suggest upregulation of O-GlcNAc in the ependyma, tectofugal neuron bodies, and radial glial processes, but not in axons. In contrast, double-label immunostaining of monolayer cultures made from dissociated embryonic day (E) 7 optic tecta revealed O-GlcNAcylation of most axons. Labeling of brain sections together with Western blot analyses showed O-GlcNAc modification of a few discrete proteins throughout development, and suggested vimentin as the protein in radial glia. Immunoprecipitation of vimentin from E9 whole brain lysates confirmed O-GlcNAcylation of vimentin in development. These results indicate a regulated pattern of O-GlcNAc modification of vimentin filaments, which in turn suggests a role for O-GlcNAc-modified intermediate filaments in radial glia, but not in neurons during brain development. The control mechanisms that regulate this pattern in vivo, however, are disrupted when cells are placed in vitro.

Specimen preparation, imaging, and analysis protocols for knife-edge scanning microscopy.

PubMed

Choe, Yoonsuck; Mayerich, David; Kwon, Jaerock; Miller, Daniel E; Sung, Chul; Chung, Ji Ryang; Huffman, Todd; Keyser, John; Abbott, Louise C

2011-12-09

Major advances in high-throughput, high-resolution, 3D microscopy techniques have enabled the acquisition of large volumes of neuroanatomical data at submicrometer resolution. One of the first such instruments producing whole-brain-scale data is the Knife-Edge Scanning Microscope (KESM), developed and hosted in the authors' lab. KESM has been used to section and image whole mouse brains at submicrometer resolution, revealing the intricate details of the neuronal networks (Golgi), vascular networks (India ink), and cell body distribution (Nissl). The use of KESM is not restricted to the mouse nor the brain. We have successfully imaged the octopus brain, mouse lung, and rat brain. We are currently working on whole zebra fish embryos. Data like these can greatly contribute to connectomics research; to microcirculation and hemodynamic research; and to stereology research by providing an exact ground-truth. In this article, we will describe the pipeline, including specimen preparation (fixing, staining, and embedding), KESM configuration and setup, sectioning and imaging with the KESM, image processing, data preparation, and data visualization and analysis. The emphasis will be on specimen preparation and visualization/analysis of obtained KESM data. We expect the detailed protocol presented in this article to help broaden the access to KESM and increase its utilization.

Brain segmentation and forebrain development in amniotes.

PubMed

Puelles, L

2001-08-01

This essay contains a general introduction to the segmental paradigm postulated for interpreting morphologically cellular and molecular data on the developing forebrain of vertebrates. The introduction examines the nature of the problem, indicating the role of topological analysis in conjunction with analysis of various developmental cell processes in the developing brain. Another section explains how morphological analysis in essence depends on assumptions (paradigms), which should be reasonable and well founded in other research, but must remain tentative until time reveals their necessary status as facts for evolving theories (or leads to their substitution by alternative assumptions). The chosen paradigm affects many aspects of the analysis, including the sectioning planes one wants to use and the meaning of what one sees in brain sections. Dorsoventral patterning is presented as the fundament for defining what is longitudinal, whereas less well-understood anteroposterior patterning results from transversal regionalization. The concept of neural segmentation is covered, first historically, and then step by step, explaining the prosomeric model in basic detail, stopping at the diencephalon, the extratelencephalic secondary prosencephalon, and the telencephalon. A new pallial model for telencephalic development and evolution is presented as well, updating the proposed homologies between the sauropsidian and mammalian telencephalon.

Propidium iodide staining: a new application in fluorescence microscopy for analysis of cytoarchitecture in adult and developing rodent brain.

PubMed

Hezel, Marcus; Ebrahimi, Fahim; Koch, Marco; Dehghani, Faramarz

2012-10-01

Immunohistochemical visualization of antigens in specimen has evolved to an indispensable technique in biomedical research for investigations of cell morphology and pathology both in bright field and fluorescence microscopy. While there are couple of staining methods that reveal entire cytoarchitecture in bright field microscopy such as Nissl or hemalaun-eosin, there are still limitations in visualizations of cytoarchitecture in fluorescence microscopy. The present study reports a simple staining method that provides the required illustration of cell allocations and cellular composition in fluorescence microscopy in adult and in developing rodent central nervous system using the fluorophore propidium iodide (PI, 5μg/mL). PI is a well-accepted marker for degenerating cells when applied prior to fixation (pre-fixation PI staining). Here, PI was added to the sections after the fixation (post-fixation PI staining). This revised labeling procedure led to similar cytoarchitectural staining patterns in fluorescence microscopy as observed with hemalaun in bright field microscopy. This finding was proven in organotypic hippocampal slice cultures (OHSC) and brain sections obtained from different postnatal developmental stages. Excitotoxically lesioned OHSC subjected to pre-fixation PI staining merely showed brightly labeled condensed nuclei of degenerating neurons. In contrast, post-fixation PI staining additionally revealed extensive labeling of neuronal cell bodies and glial cells within the OHSC, thus allowing visualization of stratification of neuronal layers and cell morphology. Furthermore, post-fixation PI staining was combined with NeuN, calbindin, calretinin, glial fibrillary acidic protein or Griffonia simplicifolia isolectin B4 (IB(4)) in post natal (p1 and p9) and adult rats. In early post-natal brain sections almost all mentioned cellular markers led to an incomplete staining of the native cell organization and resulted in an inaccurate estimation of cell morphology when compared to adult brains. In contrast, post-fixation PI staining allowed investigation of the whole cytoarchitecture independent of the developmental stage. Taken together, post-fixation PI staining provides a detailed insight in the morphology of both developing and adult brain tissues in fluorescence microscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging.

PubMed

Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

2016-09-06

Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.

Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo

PubMed Central

Laperchia, Claudia; Allegra Mascaro, Anna L.; Sacconi, Leonardo; Andrioli, Anna; Mattè, Alessandro; De Franceschi, Lucia; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Buffelli, Mario; Pavone, Francesco S.

2013-01-01

Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions. PMID:23409142

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

PubMed

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

2014-10-01

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

Investigating the impact of blood pressure increase to the brain using high resolution serial histology and image processing

NASA Astrophysics Data System (ADS)

Lesage, F.; Castonguay, A.; Tardif, P. L.; Lefebvre, J.; Li, B.

2015-09-01

A combined serial OCT/confocal scanner was designed to image large sections of biological tissues at microscopic resolution. Serial imaging of organs embedded in agarose blocks is performed by cutting through tissue using a vibratome which sequentially cuts slices in order to reveal new tissue to image, overcoming limited light penetration encountered in microscopy. Two linear stages allow moving the tissue with respect to the microscope objective, acquiring a 2D grid of volumes (1x1x0.3 mm) with OCT and a 2D grid of images (1x1mm) with the confocal arm. This process is repeated automatically, until the entire sample is imaged. Raw data is then post-processed to re-stitch each individual acquisition and obtain a reconstructed volume of the imaged tissue. This design is being used to investigate correlations between white matter and microvasculature changes with aging and with increase in pulse pressure following transaortic constriction in mice. The dual imaging capability of the system allowed to reveal different contrast information: OCT imaging reveals changes in refractive indices giving contrast between white and grey matter in the mouse brain, while transcardial perfusion of FITC or pre-sacrifice injection of Evans Blue shows microsvasculature properties in the brain with confocal imaging.

Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template.

PubMed

Majka, Piotr; Chaplin, Tristan A; Yu, Hsin-Hao; Tolpygo, Alexander; Mitra, Partha P; Wójcik, Daniel K; Rosa, Marcello G P

2016-08-01

The marmoset is an emerging animal model for large-scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl-stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We applied this procedure to 17 injections, placed in the frontal lobe of nine marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as Supplementary Materials. Comparison between the results of the automated and human-based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated (r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large datasets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain. J. Comp. Neurol. 524:2161-2181, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Whole-brain serial-section electron microscopy in larval zebrafish.

PubMed

Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

2017-05-18

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

Whole-brain serial-section electron microscopy in larval zebrafish

NASA Astrophysics Data System (ADS)

Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

2017-05-01

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

PubMed

Dai, Yu-Jie; Zhang, Xin; Yang, Yang; Nan, Hai-Yan; Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Bo; Zhang, Jin; Qiu, Zi-Yu; Gao, Yi; Cui, Guang-Bin; Chen, Bi-Liang; Wang, Wen

2018-03-14

The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

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

Neural Plasticity and Neurorehabilitation Following Traumatic Brain Injury

DTIC Science & Technology

2010-10-01

for sectioning and staining . To date, the brains have been sectioned and one set stained for Nissl . Using the Nissl stained sections, Dorothy...all behavioral data. • Brains have been harvested and sent to Dr. Jones’ lab • Dr. Jones’ lab has sliced the brains and stained one set with Nissl ...remaining sets of brain sections are currently being stained with markers of plasticity using immunohistochemistry. We have completed immunohistochemical

Preclinical Evaluation of 18F-JNJ64349311, a Novel PET Tracer for Tau Imaging.

PubMed

Declercq, Lieven; Rombouts, Frederik; Koole, Michel; Fierens, Katleen; Mariën, Jonas; Langlois, Xavier; Andrés, José Ignacio; Schmidt, Mark; Macdonald, Gregor; Moechars, Diederik; Vanduffel, Wim; Tousseyn, Thomas; Vandenberghe, Rik; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

2017-06-01

In this study, we have synthesized and evaluated 18 F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500×) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18 F-AV1451 ( 18 F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18 F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ∼1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time-activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18 F-JNJ64349311 is a promising tau PET tracer candidate, with a favorable pharmacokinetic profile, as compared with 18 F-AV1451. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Informant Report of Financial Capacity for Individuals With Chronic Acquired Brain Injury: An Assessment of Informant Accuracy.

PubMed

Sunderaraman, Preeti; Cosentino, Stephanie; Lindgren, Karen; James, Angela; Schultheis, Maria

2018-03-29

Primarily, to investigate the association between informant report and objective performance on specific financial capacity (FC) tasks by adults with chronic, moderate to severe acquired brain injury, and to examine the nature of misestimates by the informants. Cross-sectional design. A postacute, community-based rehabilitation center. Data were obtained from 22 chronic acquired brain injury (CABI) adults, mean age of 46.6 years (SD = 8.67), mean years of education of 13.45 years (SD = 2.15), with moderate to severe acquired brain injury (86% had traumatic brain injury), with a mean postinjury period of 17.14 years (SD = 9.5). Whereas the CABI adults completed the Financial Competence Assessment Inventory interview-a combination of self-report and performance-based assessment, 22 informants completed a specifically designed parallel version of the interview. Pearson correlations and 1-sample t tests based on the discrepancy scores between informant report and CABI group's performance were used. The CABI group's performance was not associated with its informant's perceptions. One-sample t tests revealed that informants both underestimated and overestimated CABI group's performance. Results indicate lack of correspondence between self- and informant ratings. Further investigation revealed that misestimations by informants occurred in contrary directions with CABI adults' performance being inaccurately rated. These findings raise critical issues related to assuming that the informant report can be used as a "gold standard" for collecting functional data related to financial management, and the idea that obtaining objective data on financial tasks may represent a more valid method of assessing financial competency in adults with brain injury.

Magnetic Transfer Contrast Accurately Localizes Substantia Nigra Confirmed by Histology

PubMed Central

Bolding, Mark S.; Reid, Meredith A.; Avsar, Kathy B.; Roberts, Rosalinda C.; Gamlin, Paul D.; Gawne, Timothy J.; White, David M.; den Hollander, Jan A.; Lahti, Adrienne C.

2012-01-01

Background Magnetic Resonance Imaging (MRI) has multiple contrast mechanisms. Like various staining techniques in histology, each contrast type reveals different information about the structure of the brain. However, it is not always clear how structures visible in MRI correspond to structures previously identified by histology. The purpose of this study was to determine if magnetic transfer contrast (MTC) or T2 contrast MRI was better at delineating the substantia nigra. Methods MRI scans were acquired in-vivo from two non-human primates (NHPs). The NHPs were subsequently euthanized, perfused, and their brains sectioned for histological analyses. Each slice was photographed prior to sectioning. Each brain was sectioned into approximately 500, 40-micron sections, encompassing most of the cortex, midbrain, and dorsal parts of the hindbrain. Levels corresponding to anatomical MRI images were selected. From these, adjacent sections were stained using Kluver Barrera (myelin and cell bodies) or tyrosine hydroxylase (TH) (dopaminergic neurons) immunohistochemistry. The resulting images were coregistered to the block-face images using a moving least squares algorithm with similarity transformations. MR images were similarly coregistered to the block-face images, allowing the structures in the MRI to be identified with structures in the histological images. Results We found that hyperintense (light) areas in MTC images were coextensive with the SN as delineated histologically. The hypointense (dark) areas in T2-weighted images were not coextensive with the SN, but extended partially into the SN and partially into the cerebral peduncles. Conclusions MTC is a more accurate contrast mechanism than T2-weighting for localizing the SN in vivo. PMID:22981657

Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: a longitudinal multimodal MRI study.

PubMed

Steiger, V R; Brühl, A B; Weidt, S; Delsignore, A; Rufer, M; Jäncke, L; Herwig, U; Hänggi, J

2017-08-01

Social anxiety disorder (SAD) is characterized by fears of social and performance situations. Cognitive behavioral group therapy (CBGT) has in general positive effects on symptoms, distress and avoidance in SAD. Prior studies found increased cortical volumes and decreased fractional anisotropy (FA) in SAD compared with healthy controls (HCs). Thirty-three participants diagnosed with SAD attended in a 10-week CBGT and were scanned before and after therapy. We applied three neuroimaging methods-surface-based morphometry, diffusion tensor imaging and network-based statistics-each with specific longitudinal processing protocols, to investigate CBGT-induced structural brain alterations of the gray and white matter (WM). Surface-based morphometry revealed a significant cortical volume reduction (pre- to post-treatment) in the left inferior parietal cortex, as well as a positive partial correlation between treatment success (indexed by reductions in Liebowitz Social Anxiety Scale) and reductions in cortical volume in bilateral dorsomedial prefrontal cortex. Diffusion tensor imaging analysis revealed a significant increase in FA in bilateral uncinate fasciculus and right inferior longitudinal fasciculus. Network-based statistics revealed a significant increase of structural connectivity in a frontolimbic network. No partial correlations with treatment success have been found in WM analyses. For, we believe, the first time, we present a distinctive pattern of longitudinal structural brain changes after CBGT measured with three established magnetic resonance imaging analyzing techniques. Our findings are in line with previous cross-sectional, unimodal SAD studies and extent them by highlighting anatomical brain alterations that point toward the level of HCs in parallel with a reduction in SAD symptomatology.

Proflavine derivatives as fluorescent imaging agents of amyloid deposits.

PubMed

Garin, Dominique; Oukhatar, Fatima; Mahon, Andrew B; Try, Andrew C; Dubois-Dauphin, Michel; Laferla, Frank M; Demeunynck, Martine; Sallanon, Marcelle Moulin; Chierici, Sabine

2011-04-15

A series of proflavine derivatives for use to further image Aβ amyloid deposits were synthesized and characterized. Aged 3xTg-AD (23 months old) mice hippocampus sections incubated with these derivatives revealed preferential labeling of amyloid plaques. Furthermore an in vitro binding study showed an inhibitory effect, although moderate, of these compounds on Aβ(40) fibril formation. This study highlights the potential of proflavine as a molecular scaffold for designing new Aβ imaging agents, its native fluorescence allowing in vitro neuropathological staining in AD damaged brain sections. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rabies-induced spongiform change and encephalitis in a heifer.

PubMed

Foley, G L; Zachary, J F

1995-05-01

A 1-year-old mixed breed heifer was presented to the Veterinary Medical Teaching Hospital at the University of Illinois with a 3-day history of abnormal mentation and aggressive behavior. Based on the history and clinical examination, euthanasia and necropsy were recommended. The differential diagnosis included rabies, pseudorabies, and a brain abscess. The brain was removed within 60 minutes of death, and the section submitted for fluorescent antibody testing was positive for rabies virus antigen. Residual brain tissue was immersion fixed in 10% neutral buffered formalin. Histologic examination revealed a marked perivascular and meningeal lymphocytic meningoencephalitis and locally extensive spongiform change of the gray matter affecting the neuropil and neuron cell bodies. The most severely affected regions with spongiform change were the thalamus and cerebral cortex. No Negri bodies were found in any sections. Since the outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom, there has been an increased surveillance of bovine neurologic cases in an effort to assess if BSE has occurred in the USA. In areas where rabies virus is endemic, rabies should be included as a possible differential diagnosis in cases of spongiform changes of the central nervous system.

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.

Development of Human Brain Structural Networks Through Infancy and Childhood

PubMed Central

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-01-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival.

PubMed

Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher

2010-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.

Differences in Brain Structure and Function in Older Adults with Self-Reported Disabling and Non-Disabling Chronic Low Back Pain

PubMed Central

Buckalew, Neilly; Haut, Marc W.; Aizenstein, Howard; Morrow, Lisa; Perera, Subashan; Kuwabara, Hiroto; Weiner, Debra K.

2010-01-01

Objective The primary aim of this pilot study was to identify structural and functional brain differences in older adults with self-reported disabling chronic low back pain (CLBP) compared with those who reported non-disabling CLBP. Design Cross-sectional. Participants Sixteen cognitively intact older adults, eight with disabling CLBP and eight with non-disabling. Exclusions were psychiatric or neurological disorders, substance abuse, opioid use, or diabetes mellitus. Methods Participants underwent: structural and functional brain MRI; neuropsychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Tests A and B; and physical performance assessment using the Short Physical Performance Battery. Results In the disabled group there was significantly lower white matter (WM) integrity (P < 0.05) of the splenium of the corpus callosum. This group also demonstrated activation of the right medial prefrontal cortex at rest whereas the non-disabled demonstrated activation of the left lateral prefrontal cortex. Combined groups analysis revealed a strong positive correlation (rs = 0.80, P < 0.0002) between WM integrity of the left centrum semiovale with gait-speed. Secondary analysis revealed a strong negative correlation between total months of CLBP and WM integrity of the SCC (rs = −0.59, P < 0.02). Conclusions Brain structure and function is different in older adults with disabling CLBP compared to those with non-disabling CLBP. Deficits in brain morphology combining groups are associated with pain duration and poor physical function. Our findings suggest brain structure and function may play a key role in chronic-pain-related-disability and may be important treatment targets. PMID:20609128

Imaging Taurine in the Central Nervous System Using Chemically Specific X-ray Fluorescence Imaging at the Sulfur K-Edge

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

Hackett, Mark J.; Paterson, Phyllis G.; Pickering, Ingrid J.

A method to image taurine distributions within the central nervous system and other organs has long been sought. Since taurine is small and mobile, it cannot be chemically “tagged” and imaged using conventional immuno-histochemistry methods. Combining numerous indirect measurements, taurine is known to play critical roles in brain function during health and disease and is proposed to act as a neuro-osmolyte, neuro-modulator, and possibly a neuro-transmitter. Elucidation of taurine’s neurochemical roles and importance would be substantially enhanced by a direct method to visualize alterations, due to physiological and pathological events in the brain, in the local concentration of taurine atmore » or near cellular spatial resolution in vivo or in situ in tissue sections. We thus have developed chemically specific X-ray fluorescence imaging (XFI) at the sulfur K-edge to image the sulfonate group in taurine in situ in ex vivo tissue sections. To our knowledge, this represents the first undistorted imaging of taurine distribution in brain at 20 μm resolution. We report quantitative technique validation by imaging taurine in the cerebellum and hippocampus regions of the rat brain. Further, we apply the technique to image taurine loss from the vulnerable CA1 (cornus ammonis 1) sector of the rat hippocampus following global brain ischemia. The location-specific loss of taurine from CA1 but not CA3 neurons following ischemia reveals osmotic stress may be a key factor in delayed neurodegeneration after a cerebral ischemic insult and highlights the significant potential of chemically specific XFI to study the role of taurine in brain disease.« less

Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

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

Ebersole, B.L.J.

The localization of (/sup 3/H)-d-lysergic acid diethylamide ((/sup 3/H)LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with (/sup 3/H)LSD in vitro revealed substantial specific (/sup 3/H)LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received (/sup 3/H)LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies ofmore » brain areas from mice that received injections of (/sup 3/H)LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free (/sup 3/H)LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of (/sup 3/H)LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of (/sup 3/H)LSD binding in hippocampus was attributable to a lower density of sites labeled by (/sup 3/H)LSD. The pharmacological identify of (/sub 3/H)LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.« less

[The comparative pathomorphological evaluation of the mice-recipient's brain cell-tissue reactions by the intracerebral imlantation of syngeneic and allogeneic neural cells].

PubMed

Liubych, L D; Semenova, V M; Lisianyĭ, M I

2013-01-01

The aim of the study was to compare the mice-recipient's brain tissue cell-structural reactions in response to intracerebral implantation of syngeneic and allogeneic cell suspensions of neural progenitor cells (NPC) (E13-15). The NPC suspensions from mice-donors of C57BL/6 and CBA containing 72.7 +/- 9.9% Vimentin+ and 81, 812, 5% GFAP+ cells were inoculated by standard procedure in right temporal segment of cerebral hemisphere of mice-recipients C57BL/6 (1 x 10(6) cells per animal). The certain part of mice-recipients of allogeneic NPC were immunosupressed by Sandimmune (100 mkg per animal) on day 0, 3, 6 after neurotransplantation. The standard histological preparations of mice brains were performed after 24 hours, 6, 12, 18 and 37 days after NPC neurotransplantation, which were investigated by cytoanalyzer "IBAS" (Germany). After intracerebral inoculation of allogeneic foetal NPC the signs of the pericellular edema and lymphocyte infiltration were detected in adjacent brain sections on day 12-18 and decreased on day 37. Allogeneic foetal NPC were reserved till day 18 and revealed the signs of primary differentiation. After immunosupression by "Sandimmune" the foetal NPC underwent the phoenotypic differentiation and infiltration in related brain sections. On the day 37 the implanted NPC were not detected. Focal reaction of the brain glial component to implanted NPC declined faster after syngeneic NPC neuroimplantation (up to day 18) than after allogeneic NPC neuroimplantation (up to day 37). After the syngeneic NPC inoculation on the 37th day at the site of implantation the formation of a small fragment of immature bone was fixed, which may indicate the possibility of NPC transdifferentiation in other cell types.

Expression of the ADHD candidate gene Diras2 in the brain.

PubMed

Grünewald, Lena; Becker, Nils; Camphausen, Annika; O'Leary, Aet; Lesch, Klaus-Peter; Freudenberg, Florian; Reif, Andreas

2018-06-01

The distinct subgroup of the Ras family member 2 (DIRAS2) gene has been found to be associated with attention-deficit/hyperactivity disorder (ADHD) in one of our previous studies. This gene is coding for a small Ras GTPase with unknown function. DIRAS2 is highly expressed in the brain. However, the exact neural expression pattern of this gene was unknown so far. Therefore, we investigated the expressional profile of DIRAS2 in the human and murine brain. In the present study, qPCR analyses in the human and in the developing mouse brain, immunocytological double staining on murine hippocampal primary cells and RNA in situ hybridization (ISH) on brain sections of C57BL/6J wild-type mice, have been used to reveal the expression pattern of DIRAS2 in the brain. We could show that DIRAS2 expression in the human brain is the highest in the hippocampus and the cerebral cortex, which is in line with the ISH results in the mouse brain. During mouse brain development, Diras2 levels strongly increase from prenatal to late postnatal stages. Co-expression studies indicate Diras2 expression in glutamatergic and catecholaminergic neurons. Our findings support the idea of DIRAS2 as a candidate gene for ADHD as the timeline of its expression as well as the brain regions and cell types that show Diras2 expression correspond to those assumed to underlie the pathomechanisms of the disease.

Predicting parenting stress in caregivers of children with brain tumours.

PubMed

Bennett, Emily; English, Martin William; Rennoldson, Michael; Starza-Smith, Arleta

2013-03-01

The purpose of the study was to identify factors that contribute to parenting stress in caregivers of children diagnosed with brain tumours. The study was cross-sectional and recruited 37 participants from a clinical database at a specialist children's hospital. Parents were sent questionnaires, which were used to measure factors related to stress in caregivers of children diagnosed with a brain tumour. Stress levels were measured using the Parenting Stress Index-Short Form (PSI/SF). Correlation analysis and multiple linear regression were used to examine the associations between parenting stress and coping styles, locus of control, parent-perceived child disability and time since diagnosis. Results revealed that 51% of parents were experiencing clinically significant levels of stress. The mean stress level of parents in the study was significantly higher than the PSI/SF norms (t = 4.7, p < .001). Regression analysis revealed that external locus of control and coping by accepting responsibility accounted for 67% of the variance in parenting stress. Other styles of coping, child behaviour problems and the amount of time since diagnosis were not found to be predictive of levels of parenting stress. There was a high prevalence of parenting stress in caregivers of children with a brain tumour. An external locus of control and coping by accepting responsibility increased the likelihood of elevated levels of stress. Results emphasised the importance of ongoing support for parents of children with brain tumours. Intervention might helpfully be centred on strategies to increase parents' internal locus of control. Copyright © 2012 John Wiley & Sons, Ltd.

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

NASA Astrophysics Data System (ADS)

Shariatgorji, Mohammadreza; Nilsson, Anna; Källback, Patrik; Karlsson, Oskar; Zhang, Xiaoqun; Svenningsson, Per; Andren, Per E.

2015-06-01

Many neuroactive substances, including endogenous biomolecules, environmental compounds, and pharmaceuticals possess primary amine functional groups. Among these are catecholamine neurotransmitters (e.g., dopamine), many substituted phenethylamines (e.g., amphetamine), as well as amino acids and neuropeptides. In most cases, mass spectrometric (ESI and MALDI) analyses of trace amounts of such compounds are challenging because of their poor ionization properties. We present a method for chemical derivatization of primary amines by reaction with pyrylium salts that facilitates their detection by MALDI-MS and enables the imaging of primary amines in brain tissue sections. A screen of pyrylium salts revealed that the 2,4-diphenyl-pyranylium ion efficiently derivatizes primary amines and can be used as a reactive MALDI-MS matrix that induces both derivatization and desorption. MALDI-MS imaging with such matrix was used to map the localization of dopamine and amphetamine in brain tissue sections and to quantitatively map the distribution of the neurotoxin β- N-methylamino-L-alanine.

A Collection of Brain Sections of "Euthanasia" Victims: The Series H of Julius Hallervorden.

PubMed

Wässle, Heinz

2017-12-01

Julius Hallervorden, a distinguished German neuropathologist, admitted on several occasions that he had received some five hundred brains of "euthanasia" victims from the Nazi killing centres for the insane. He investigated the brains in the summer of 1942; however, their traces were subsequently lost. The present study shows, that the Series H, which was part of the Hallervorden collection of brain sections in the Max Planck Institute for Brain Research, comprises the brain sections of the above mentioned five hundred euthanasia victims. The provenance of 105 patients could be reconstructed and 84 are for sure euthanasia victims. Most of them were killed in Bernburg or in Sonnenstein-Pirna. Hallervorden used the brain sections of Series H until 1956 for his studies and never publicly regretted this abuse of the brains of euthanasia victims. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

Cofran, Zachary

2018-05-24

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

Glucose and oxygen metabolism after penetrating ballistic-like brain injury

PubMed Central

Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

2015-01-01

Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies. PMID:25669903

Glucose and oxygen metabolism after penetrating ballistic-like brain injury.

PubMed

Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

2015-05-01

Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies.

Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis.

PubMed

De Maria, R; Divari, S; Bo, S; Sonnio, S; Lotti, D; Capucchio, M T; Castagnaro, M

1998-09-01

A 7-month-old Korat cat was referred for a slowly progressive neurological disease. Circulating monocytes and lymphocytes showed the presence of single or multiple empty vacuoles and blood leukocytes enzyme assay revealed a very low beta-galactosidase activity level (4.7 nmol/mg per h) as compared to unaffected parents and relatives. Histologically, the cat, euthanized at the owner request at 21 months of age, presented diffuse vacuolization and enlargement of neurons throughout the brain, spinal cord and peripheral ganglia, severe cerebellar neuronal cell loss, and moderate astrocytosis. Stored material was stained with periodic acid-Schiff on frozen sections and with the lectins Ricinus conmmunis agglutinin-I, concanavalin A and wheat germ agglutinin on paraffin-embedded sections. Ultrastructurally, neuronal vacuoles were filled with concentrically whorled lamellae and small membrane-bound vesicles. In the affected cat, beta-galactosidase activity was markedly reduced in brain (18.9%) and liver (33.25%), while total beta-hexosaminidase activity showed a remarkable increase. Quantitation of total gangliosides revealed a 3-fold increase in brain and 1.7-fold in liver of affected cat. High-performance thin layer chromatography (HPTLC) detected a striking increase of GM1-ganglioside. On densitometric analysis of HPTLC bands, the absorption of GM1-ganglioside band was 98.52% of all stained bands (GD1a, GD1b, GT1b). Based on clinical onset, morphological and histochemical features, and biochemical findings, the Korat cat GM1-gangliosidosis is comparable with the human type II (juvenile) form. However, clinical progression, survival time and level of beta-galactosidase deficiency do not completely fit with those of human type II GM1-gangliosidosis. The disease in the Korat cat is also different from other reported forms of feline GM1-gangliosidosis.

Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review.

PubMed

Keightley, Michelle L; Sinopoli, Katia J; Davis, Karen D; Mikulis, David J; Wennberg, Richard; Tartaglia, Maria C; Chen, Jen-Kai; Tator, Charles H

2014-01-01

While generalized cerebral atrophy and neurodegenerative change following traumatic brain injury (TBI) is well recognized in adults, it remains comparatively understudied in the pediatric population, suggesting that research should address the potential for neurodegenerative change in children and youth following TBI. This focused review examines original research findings documenting evidence for neurodegenerative change following TBI of all severities in children and youth. Our relevant inclusion and exclusion criteria identified a total of 16 articles for review. Taken together, the studies reviewed suggest there is evidence for long-term neurodegenerative change following TBI in children and youth. In particular both cross-sectional and longitudinal studies revealed volume loss in selected brain regions including the hippocampus, amygdala, globus pallidus, thalamus, periventricular white matter, cerebellum, and brain stem as well as overall decreased whole brain volume and increased CSF and ventricular space. Diffusion Tensor Imaging (DTI) studies also report evidence for decreased cellular integrity, particularly in the corpus callosum. Sensitivity of the hippocampus and deep limbic structures in pediatric populations are similar to findings in the adult literature and we consider the data supporting these changes as well as the need to investigate the possibility of neurodegenerative onset in childhood associated with mild traumatic brain injury (mTBI).

Concomitant fractional anisotropy and volumetric abnormalities in temporal lobe epilepsy: cross-sectional evidence for progressive neurologic injury.

PubMed

Keller, Simon S; Schoene-Bake, Jan-Christoph; Gerdes, Jan S; Weber, Bernd; Deppe, Michael

2012-01-01

In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.

Mapping of Courtship Behavior-Induced Neural Activity in the Thoracic Ganglia of Silkmoth Bombyx mori by an Immediate Early Gene, Hr38.

PubMed

Morishita, Koudai; Iwami, Masafumi; Kiya, Taketoshi

2018-06-01

In the central nervous system of insects, motor patterns are generated in the thoracic ganglia under the control of brain, where sensory information is integrated and behavioral decisions are made. Previously, we established neural activity-mapping methods using an immediate early gene, BmHr38, as a neural activity marker in the brain of male silkmoth Bombyx mori. In the present study, to gain insights into neural mechanisms of motor-pattern generation in the thoracic ganglia, we investigated expression of BmHr38 in response to sex pheromone-induced courtship behavior. Levels of BmHr38 expression were strongly correlated between the brain and thoracic ganglia, suggesting that neural activity in the thoracic ganglia is tightly controlled by the brain. In situ hybridization of BmHr38 revealed that 20-30% of thoracic neurons are activated by courtship behavior. Using serial sections, we constructed a comprehensive map of courtship behaviorinduced activity in the thoracic ganglia. These results provide important clues into how complex courtship behavior is generated in the neural circuits of thoracic ganglia.

Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer.

PubMed

Tago, Tetsuro; Furumoto, Shozo; Okamura, Nobuyuki; Harada, Ryuichi; Adachi, Hajime; Ishikawa, Yoichi; Yanai, Kazuhiko; Iwata, Ren; Kudo, Yukitsuka

2016-04-01

Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer's disease (AD). Recently, we have developed [(18)F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [(18)F]THK-5105 enantiomers. Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assay The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that (S)-[(18)F]THK-5105 has slower dissociation from tau than (R)-[(18)F]THK-5105. Biodistribution assays indicated that (S)-[(18)F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[(18)F]THK-5105. (S)-[(18)F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.

A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

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

Laig-Webster, M.; Lim, M.E.; Chehab, F.F.

1994-09-01

The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing tomore » the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.« less

Development of human brain structural networks through infancy and childhood.

PubMed

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-05-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Large-Scale Mass Spectrometry Imaging Investigation of Consequences of Cortical Spreading Depression in a Transgenic Mouse Model of Migraine

NASA Astrophysics Data System (ADS)

Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Abdelmoula, Walid M.; van Heiningen, Sandra H.; van Zeijl, Rene J.; Dijkstra, Jouke; Ferrari, Michel D.; Tolner, Else A.; McDonnell, Liam A.; van den Maagdenberg, Arn M. J. M.

2015-06-01

Cortical spreading depression (CSD) is the electrophysiological correlate of migraine aura. Transgenic mice carrying the R192Q missense mutation in the Cacna1a gene, which in patients causes familial hemiplegic migraine type 1 (FHM1), exhibit increased propensity to CSD. Herein, mass spectrometry imaging (MSI) was applied for the first time to an animal cohort of transgenic and wild type mice to study the biomolecular changes following CSD in the brain. Ninety-six coronal brain sections from 32 mice were analyzed by MALDI-MSI. All MSI datasets were registered to the Allen Brain Atlas reference atlas of the mouse brain so that the molecular signatures of distinct brain regions could be compared. A number of metabolites and peptides showed substantial changes in the brain associated with CSD. Among those, different mass spectral features showed significant ( t-test, P < 0.05) changes in the cortex, 146 and 377 Da, and in the thalamus, 1820 and 1834 Da, of the CSD-affected hemisphere of FHM1 R192Q mice. Our findings reveal CSD- and genotype-specific molecular changes in the brain of FHM1 transgenic mice that may further our understanding about the role of CSD in migraine pathophysiology. The results also demonstrate the utility of aligning MSI datasets to a common reference atlas for large-scale MSI investigations.

Interaction of Aluminum with PHFτ in Alzheimer’s Disease Neurofibrillary Degeneration Evidenced by Desferrioxamine-Assisted Chelating Autoclave Method

PubMed Central

Murayama, Harunobu; Shin, Ryong-Woon; Higuchi, Jun; Shibuya, Satoshi; Muramoto, Tamaki; Kitamoto, Tetsuyuki

1999-01-01

To demonstrate that aluminum III (Al) interacts with PHFτ in neurofibrillary degeneration (NFD) of Alzheimer’s disease (AD) brain, we developed a “chelating autoclave method” that allows Al chelation by using trivalent-cationic chelator desferrioxamine. Its application to AD brain sections before Morin histochemistry for Al attenuated the positive fluorescence of neurofibrillary tangles, indicating Al removal from them. This method, applied for immunostaining with phosphorylation-dependent anti-τ antibodies, significantly enhanced the PHFτ immunoreactivity of the NFD. These results suggest that each of the phosphorylated epitopes in PHFτ are partially masked by Al binding. Incubation of AD sections with AlCl3 before Morin staining revealed Al accumulation with association to neurofibrillary tangles. Such incubation before immunostaining with the phosphorylation-dependent anti-τ antibodies abolished the immunolabeling of the NFD and this abolition was reversed by the Al chelation. These findings indicate cumulative Al binding to and thereby antigenic masking of the phosphorylated epitopes of PHFτ. Al binding was further documented for electrophoretically-resolved PHFτ on immunoblots, indicating direct Al binding to PHFτ. In vitro aggregation by AlCl3 was observed for PHFτ but was lost on dephosphorylation of PHFτ. Taken together, phosphorylation-dependent and direct PHFτ-Al interaction occurs in the NFD of the AD brain. PMID:10487845

Gray Matter Atrophy in the Cerebellum-Evidence of Increased Vulnerability of the Crus and Vermis with Advancing Age.

PubMed

Yu, Teresa; Korgaonkar, Mayuresh S; Grieve, Stuart M

2017-04-01

This study examined patterns of cerebellar volumetric gray matter (GM) loss across the adult lifespan in a large cross-sectional sample. Four hundred and seventy-nine healthy participants (age range: 7-86 years) were drawn from the Brain Resource International Database who provided T1-weighted MRI scans. The spatially unbiased infratentorial template (SUIT) toolbox in SPM8 was used for normalisation of the cerebellum structures. Global volumetric and voxel-based morphometry analyses were performed to evaluate age-associated trends and gender-specific age-patterns. Global cerebellar GM shows a cross-sectional reduction with advancing age of 2.5 % per decade-approximately half the rate seen in the whole brain. The male cerebellum is larger with a lower percentage of GM, however, after controlling for total brain volume, no gender difference was detected. Analysis of age-related changes in GM volume revealed large bilateral clusters involving the vermis and cerebellar crus where regional loss occurred at nearly twice the average cerebellar rate. No gender-specific patterns were detected. These data confirm that regionally specific GM loss occurs in the cerebellum with age, and form a solid base for further investigation to find functional correlates for this global and focal loss.

Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue.

PubMed

Hsieh, Yunsheng; Casale, Roger; Fukuda, Elaine; Chen, Jiwen; Knemeyer, Ian; Wingate, Julia; Morrison, Richard; Korfmacher, Walter

2006-01-01

Matrix-assisted laser desorption/ionization hyphenated with quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been used to directly determine the distribution of pharmaceuticals in rat brain tissue slices which might unravel their disposition for new drug development. Clozapine, an antipsychotic drug, and norclozapine were used as model compounds to investigate fundamental parameters such as matrix and solvent effects and irradiance dependence on MALDI intensity but also to address the issues with direct tissue imaging MS technique such as (1) uniform coating by the matrix, (2) linearity of MALDI signals, and (3) redistribution of surface analytes. The tissue sections were coated with various matrices on MALDI plates by airspray deposition prior to MS detection. MALDI signals of analytes were detected by monitoring the dissociation of the individual protonated molecules to their predominant MS/MS product ions. The matrices were chosen for tissue applications based on their ability to form a homogeneous coating of dense crystals and to yield greater sensitivity. Images revealing the spatial localization in tissue sections using MALDI-QTOF following a direct infusion of (3)H-clozapine into rat brain were found to be in good correlation with those using a radioautographic approach. The density of clozapine and its major metabolites from whole brain homogenates was further confirmed using fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) procedures. Copyright (c) 2006 John Wiley & Sons, Ltd.

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique.

PubMed

Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S; Franciotti, Neil; Weber, Kevin; Mitra, Partha P

2015-01-01

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20 μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey.

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique

PubMed Central

Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S.; Franciotti, Neil; Weber, Kevin; Mitra, Partha P.

2015-01-01

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey. PMID:26181725

A Cross-Sectional Voxel-Based Morphometric Study of Age- and Sex-Related Changes in Gray Matter Volume in the Normal Aging Brain.

PubMed

Peng, Fei; Wang, Lixin; Geng, Zuojun; Zhu, Qingfeng; Song, Zhenhu

2016-01-01

The aim of the study was to carry out a cross-sectional study of 124 cognitively normal Chinese adults using the voxel-based morphometry approach to delineate age-related changes in the gray matter volume of regions of interest (ROI) in the brain and further analyze their correlation with age. One hundred twenty-four cognitively normal adults were divided into the young age group, the middle age group, and the old age group. Conventional magnetic resonance imaging was performed with the Achieva 3.0 T system. Structural images were processed using VBM8 and SPM8. Regions of interest were obtained by WFU PickAtlas and all realigned images were spatially normalized. Females showed significantly greater total gray matter volume than males (t = 4.81, P = 0.0000, false discovery rate corrected). Compared with young subjects, old-aged subjects showed extensive reduction in gray matter volumes in all ROIs examined except the occipital lobe. In young- and middle-aged subjects, female and male subjects showed significant difference in the right middle temporal gyrus, right superior temporal gyrus, left angular gyrus, right middle occipital lobe, left middle cingulate gyrus, and the pars triangularis of the right inferior frontal gyrus, suggesting an interaction between age and sex (P < 0.001, uncorrected). Logistic regression analysis revealed linear negative correlation between the total gray matter volume and age (R = 0.529, P < 0.001). Significant age-related differences are present in gray matter volume across multiple brain regions during aging. The VPM approach may provide an emerging paradigm in the normal aging brain that may help differentiate underlying normal neurobiological aging changes of specific brain regions from neurodegenerative impairments.

Structural bases for neurophysiological investigations of amygdaloid complex of the brain

NASA Astrophysics Data System (ADS)

Kalimullina, Liliya B.; Kalkamanov, Kh. A.; Akhmadeev, Azat V.; Zakharov, Vadim P.; Sharafullin, Ildus F.

2015-11-01

Amygdala (Am) as a part of limbic system of the brain defines such important functions as adaptive behavior of animals, formation of emotions and memory, regulation of endocrine and visceral functions. We worked out, with the help of mathematic modelling of the pattern recognition theory, principles for organization of neurophysiological and neuromorphological studies of Am nuclei, which take into account the existing heterogeneity of its formations and optimize, to a great extent, the protocol for carrying out of such investigations. The given scheme of studies of Am’s structural-functional organization at its highly-informative sections can be used as a guide for precise placement of electrodes’, cannulae’s and microsensors into particular Am nucleus in the brain with the registration not only the nucleus itself, but also its extensions. This information is also important for defining the number of slices covering specific Am nuclei which must be investigated to reveal the physiological role of a particular part of amygdaloid complex.

Traumatic brain injuries in the construction industry.

PubMed

Colantonio, Angela; McVittie, Doug; Lewko, John; Yin, Junlang

2009-10-01

This study analyses factors associated with work-related traumatic brain injury (TBI), specifically in the construction industry in Ontario, Canada. This cross-sectional study utilized data extracted from the Ontario Workplace Safety and Insurance Board (WSIB) records indicating concussion/intracranial injury that resulted in days off work in 2004-2005. Analyses of 218 TBI cases revealed that falls were the most common cause of injury, followed by being struck by or against an object. Mechanisms of injury and the temporal profile of injury also varied by age. For instance, a significantly higher proportion of injuries occurred in the mornings for young workers compared to older workers. The results of this study provide important information for prevention of TBI which suggest important age-specific strategies for workers in the construction industry.

Effect of Lapatinib on the Outgrowth of Metastatic Breast Cancer Cells to the Brain

PubMed Central

Gril, Brunilde; Palmieri, Diane; Bronder, Julie L.; Herring, Jeanne M.; Vega-Valle, Eleazar; Feigenbaum, Lionel; Liewehr, David J.; Steinberg, Seth M.; Merino, Maria J.; Rubin, Stephen D.

2008-01-01

Background The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. Methods EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 μm2) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22–26 mice per treatment group). All statistical tests were two-sided. Results In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%–53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell–derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell–derived brain metastases from vehicle-treated mice (P < .001). Conclusions Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer. PMID:18664652

Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain.

PubMed

Gril, Brunilde; Palmieri, Diane; Bronder, Julie L; Herring, Jeanne M; Vega-Valle, Eleazar; Feigenbaum, Lionel; Liewehr, David J; Steinberg, Seth M; Merino, Maria J; Rubin, Stephen D; Steeg, Patricia S

2008-08-06

The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 microm(2)) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22-26 mice per treatment group). All statistical tests were two-sided. In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%-53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell-derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell-derived brain metastases from vehicle-treated mice (P < .001). Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

PubMed

Corces, M Ryan; Trevino, Alexandro E; Hamilton, Emily G; Greenside, Peyton G; Sinnott-Armstrong, Nicholas A; Vesuna, Sam; Satpathy, Ansuman T; Rubin, Adam J; Montine, Kathleen S; Wu, Beijing; Kathiria, Arwa; Cho, Seung Woo; Mumbach, Maxwell R; Carter, Ava C; Kasowski, Maya; Orloff, Lisa A; Risca, Viviana I; Kundaje, Anshul; Khavari, Paul A; Montine, Thomas J; Greenleaf, William J; Chang, Howard Y

2017-10-01

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-μm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

Ambient Molecular Analysis of Biological Tissue Using Low-Energy, Femtosecond Laser Vaporization and Nanospray Postionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Shi, Fengjian; Flanigan, Paul M.; Archer, Jieutonne J.; Levis, Robert J.

2016-03-01

Direct analysis of plant and animal tissue samples by laser electrospray mass spectrometry (LEMS) was investigated using low-energy, femtosecond duration laser vaporization at wavelengths of 800 and 1042 nm followed by nanospray postionization. Low-energy (<50 μJ), fiber-based 1042 nm LEMS (F-LEMS) allowed interrogation of the molecular species in fresh flower petal and leaf samples using 435 fs, 10 Hz bursts of 20 pulses from a Ytterbium-doped fiber laser and revealed comparable results to high energy (75-1120 μJ), 45 fs, 800 nm Ti:Sapphire-based LEMS (Ti:Sapphire-LEMS) measurements. Anthocyanins, sugars, and other metabolites were successfully detected and revealed the anticipated metabolite profile for the petal and leaf samples. Phospholipids, especially phosphatidylcholine, were identified from a fresh mouse brain section sample using Ti:Sapphire-LEMS without the application of matrix. These lipid features were suppressed in both the fiber-based and Ti:Sapphire-based LEMS measurements when the brain sample was prepared using the optimal cutting temperature compounds that are commonly used in animal tissue cryosections.

"Clinical brain profiling": a neuroscientific diagnostic approach for mental disorders.

PubMed

Peled, Abraham; Geva, Amir B

2014-10-01

Clinical brain profiling is an attempt to map a descriptive nosology in psychiatry to underlying constructs in neurobiology and brain dynamics. This paper briefly reviews the motivation behind clinical brain profiling (CBP) and presents some provisional validation using clinical assessments and meta-analyses of neuroscientific publications. The paper has four sections. In the first, we review the nature and motivation for clinical brain profiling. This involves a description of the key aspects of functional anatomy that can lead to psychopathology. These features constitute the dimensions or categories for a profile of brain disorders based upon pathophysiology. The second section describes a mapping or translation matrix that maps from symptoms and signs, of a descriptive sort, to the CBP dimensions that provide a more mechanistic explanation. We will describe how this mapping engenders archetypal diagnoses, referring readers to tables and figures. The third section addresses the construct validity of clinical brain profiling by establishing correlations between profiles based on clinical ratings of symptoms and signs under classical diagnostic categories with the corresponding profiles generated automatically using archetypal diagnoses. We then provide further validation by performing a cluster analysis on the symptoms and signs and showing how they correspond to the equivalent brain profiles based upon clinical and automatic diagnosis. In the fourth section, we address the construct validity of clinical brain profiling by looking for associations between pathophysiological mechanisms (such as connectivity and plasticity) and nosological diagnoses (such as schizophrenia and depression). Based upon the mechanistic perspective offered in the first section, we test some particular hypotheses about double dissociations using a meta-analysis of PubMed searches. The final section concludes with perspectives for the future and outstanding validation issues for clinical brain profiling. Copyright © 2014 Elsevier Ltd. All rights reserved.

An Automated Platform for High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

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

Lanekoff, Ingela T.; Heath, Brandi S.; Liyu, Andrey V.

2012-10-02

An automated platform has been developed for acquisition and visualization of mass spectrometry imaging (MSI) data using nanospray desorption electrospray ionization (nano-DESI). The new system enables robust operation of the nano-DESI imaging source over many hours. This is achieved by controlling the distance between the sample and the probe by mounting the sample holder onto an automated XYZ stage and defining the tilt of the sample plane. This approach is useful for imaging of relatively flat samples such as thin tissue sections. Custom software called MSI QuickView was developed for visualization of large data sets generated in imaging experiments. MSImore » QuickView enables fast visualization of the imaging data during data acquisition and detailed processing after the entire image is acquired. The performance of the system is demonstrated by imaging rat brain tissue sections. High resolution mass analysis combined with MS/MS experiments enabled identification of lipids and metabolites in the tissue section. In addition, high dynamic range and sensitivity of the technique allowed us to generate ion images of low-abundance isobaric lipids. High-spatial resolution image acquired over a small region of the tissue section revealed the spatial distribution of an abundant brain metabolite, creatine, in the white and gray matter that is consistent with the literature data obtained using magnetic resonance spectroscopy.« less

Site specificity of adrenalectomy-induced brain growth.

PubMed

Thomas, T L; Devenport, L D

1988-12-01

Infant, juvenile, and adult brain growth is modulated by corticosterone. This study was designed to determine whether such modulation is confined to certain specific brain areas, and if the pattern of growth revealed is consistent across strains of rats. Young female Sprague-Dawley-derived rats were either adrenalectomized (ADX) or sham-operated (Sham) and allowed to mature 45 days before they were sacrificed for histological analysis. Fore brain sections were taken at several planes for display by projection microscope. Of the 21 sites examined, ADX exerted its greatest effect upon neocortical tissue and myelinated fiber tracts. The only other brain region affected was thalamus, which exhibited a significant widening as a result of ADX. In contrast, archicortical structures were notably unaffected by ADX. Neither the hippocampus, measured from a variety of planes, nor nuclei in the septal area were subject to increased growth by ADX. This general portrayal of ADX's site specificity held across strains of rats. However, there were local differences. Within the neopallium, the frontal region underwent the greatest thickening in one strain, while the occipital area was most strongly affected in the other. Parietal cortex was equally responsive in both strains. The pattern of sensitive vs insensitive sites bore a resemblance to the pattern of increased growth brought about by environmental enrichment as well as the fore brain distribution of Type 2 corticosterone receptors.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application.

PubMed

Zahodne, Laura B; Manly, Jennifer J; Brickman, Adam M; Narkhede, Atul; Griffith, Erica Y; Guzman, Vanessa A; Schupf, Nicole; Stern, Yaakov

2015-10-01

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point. Copyright © 2015. Published by Elsevier Ltd.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application

PubMed Central

Zahodne, Laura B.; Manly, Jennifer J.; Brickman, Adam M.; Narkhede, Atul; Griffith, Erica Y.; Guzman, Vanessa A.; Schupf, Nicole; Stern, Yaakov

2016-01-01

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point. PMID:26348002

The Brain of the Archerfish Toxotes chatareus: A Nissl-Based Neuroanatomical Atlas and Catecholaminergic/Cholinergic Systems

PubMed Central

Karoubi, Naomi; Segev, Ronen; Wullimann, Mario F.

2016-01-01

Over recent years, the seven-spot archerfish (Toxotes chatareus) has emerged as a new model for studies in visual and behavioral neuroscience thanks to its unique hunting strategy. Its natural ability to spit at insects outside of water can be used in the laboratory for well controlled behavioral experiments where the fish is trained to aim at targets on a screen. The need for a documentation of the neuroanatomy of this animal became critical as more research groups use it as a model. Here we present an atlas of adult T. chatareus specimens caught in the wild in South East Asia. The atlas shows representative sections of the brain and specific structures revealed by a classic Nissl staining as well as corresponding schematic drawings. Additional immunostainings for catecholaminergic and cholinergic systems were conducted to corroborate the identification of certain nuclei and the data of a whole brain scanner is available online. We describe the general features of the archerfish brain as well as its specificities, especially for the visual system and compare the neuroanatomy of the archerfish with other teleosts. This atlas of the archerfish brain shows all levels of the neuraxis and intends to provide a solid basis for further neuroscientific research on T. chatareus, in particular electrophysiological studies. PMID:27891081

Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease.

PubMed

Pradhan, Suman; Pellino, Christine; MacMaster, Kayleigh; Coyle, Dennis; Weiss, Alison A

2016-01-01

Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli , and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed. Microglial cell responses to neural injury include up-regulation of surface-marker expression (e.g., Iba1) and stereotypical morphological changes. Mice injected with Stx2a showed increased Iba1 staining, mild morphological changes associated with microglial activation (thickening of processes), and increased microglial staining per unit area. Microglial changes were observed in the cortex, hippocampus, and amygdala regions, but not the nucleus. Magnetic resonance imaging (MRI) of Stx2a-treated mice revealed no hyper-intensities in the brain, although magnetic resonance spectroscopy (MRS) revealed significantly decreased levels of phosphocreatine in the thalamus. Less dramatic changes were observed following Stx1 challenge. Neither immortalized microvascular endothelial cells from the cerebral cortex of mice (bEnd.3) nor primary human brain microvascular endothelial cells were found to be susceptible to Stx1 or Stx2a. The lack of susceptibility to Stx for both cell types correlated with an absence of receptor expression. These studies indicate Stx causes subtle, but identifiable changes in the mouse brain.

Concomitant Fractional Anisotropy and Volumetric Abnormalities in Temporal Lobe Epilepsy: Cross-Sectional Evidence for Progressive Neurologic Injury

PubMed Central

Gerdes, Jan S.; Weber, Bernd; Deppe, Michael

2012-01-01

Background In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). Methodology/Principal Findings For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. Conclusions/Significance Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients. PMID:23071638

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PubMed

Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

2010-05-01

The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

The impact of parent-child interaction on brain structures: cross-sectional and longitudinal analyses.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Yokota, Susumu; Kotozaki, Yuka; Nouchi, Rui; Kawashima, Ryuta

2015-02-04

There is a vast amount of evidence from psychological studies that the amount of parent-child interaction affects the development of children's verbal skills and knowledge. However, despite the vast amount of literature, brain structural development associated with the amount of parent-child interaction has never been investigated. In the present human study, we used voxel-based morphometry to measure regional gray matter density (rGMD) and examined cross-sectional correlations between the amount of time spent with parents and rGMD among 127 boys and 135 girls. We also assessed correlations between the amount of time spent with parents and longitudinal changes that occurred a few years later among 106 boys and 102 girls. After correcting for confounding factors, we found negative effects of spending time with parents on rGMD in areas in the bilateral superior temporal gyrus (STG) via cross-sectional analyses as well as in the contingent areas of the right STG. We also confirmed positive effects of spending time with parents on the Verbal Comprehension score in cross-sectional and longitudinal analyses. rGMD in partly overlapping or contingent areas of the right STG was negatively correlated with age and the Verbal Comprehension score in cross-sectional analyses. Subsequent analyses revealed verbal parent-child interactions have similar effects on Verbal Comprehension scores and rGMD in the right STG in both cross-sectional and longitudinal analyses. These findings indicate that parent-child interactions affect the right STG, which may be associated with verbal skills. Copyright © 2015 the authors 0270-6474/15/352233-13$15.00/0.

Segregated Systems of Human Brain Networks.

PubMed

Wig, Gagan S

2017-12-01

The organization of the brain network enables its function. Evaluation of this organization has revealed that large-scale brain networks consist of multiple segregated subnetworks of interacting brain areas. Descriptions of resting-state network architecture have provided clues for understanding the functional significance of these segregated subnetworks, many of which correspond to distinct brain systems. The present report synthesizes accumulating evidence to reveal how maintaining segregated brain systems renders the human brain network functionally specialized, adaptable to task demands, and largely resilient following focal brain damage. The organizational properties that support system segregation are harmonious with the properties that promote integration across the network, but confer unique and important features to the brain network that are central to its function and behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reconceptualizing sex, brain and psychopathology: interaction, interaction, interaction

PubMed Central

Joel, D; Yankelevitch-Yahav, R

2014-01-01

In recent years there has been a growing recognition of the influence of sex on brain structure and function, and in relation, on the susceptibility, prevalence and response to treatment of psychiatric disorders. Most theories and descriptions of the effects of sex on the brain are dominated by an analogy to the current interpretation of the effects of sex on the reproductive system, according to which sex is a divergence system that exerts a unitary, overriding and serial effect on the form of other systems. We shortly summarize different lines of evidence that contradict aspects of this analogy. The new view that emerges from these data is of sex as a complex system whose different components interact with one another and with other systems to affect body and brain. The paradigm shift that this understanding calls for is from thinking of sex in terms of sexual dimorphism and sex differences, to thinking of sex in terms of its interactions with other factors and processes. Our review of data obtained from animal models of psychopathology clearly reveals the need for such a paradigmatic shift, because in the field of animal behaviour whether a sex difference exists and its direction depend on the interaction of many factors including, species, strain, age, specific test employed and a multitude of environmental factors. We conclude by explaining how the new conceptualization can account for sex differences in psychopathology. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24758640

The neural processing of hierarchical structure in music and speech at different timescales.

PubMed

Farbood, Morwaread M; Heeger, David J; Marcus, Gary; Hasson, Uri; Lerner, Yulia

2015-01-01

Music, like speech, is a complex auditory signal that contains structures at multiple timescales, and as such is a potentially powerful entry point into the question of how the brain integrates complex streams of information. Using an experimental design modeled after previous studies that used scrambled versions of a spoken story (Lerner et al., 2011) and a silent movie (Hasson et al., 2008), we investigate whether listeners perceive hierarchical structure in music beyond short (~6 s) time windows and whether there is cortical overlap between music and language processing at multiple timescales. Experienced pianists were presented with an extended musical excerpt scrambled at multiple timescales-by measure, phrase, and section-while measuring brain activity with functional magnetic resonance imaging (fMRI). The reliability of evoked activity, as quantified by inter-subject correlation of the fMRI responses, was measured. We found that response reliability depended systematically on musical structure coherence, revealing a topographically organized hierarchy of processing timescales. Early auditory areas (at the bottom of the hierarchy) responded reliably in all conditions. For brain areas at the top of the hierarchy, the original (unscrambled) excerpt evoked more reliable responses than any of the scrambled excerpts, indicating that these brain areas process long-timescale musical structures, on the order of minutes. The topography of processing timescales was analogous with that reported previously for speech, but the timescale gradients for music and speech overlapped with one another only partially, suggesting that temporally analogous structures-words/measures, sentences/musical phrases, paragraph/sections-are processed separately.

3D culture of murine neural stem cells on decellularized mouse brain sections.

PubMed

De Waele, Jorrit; Reekmans, Kristien; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

2015-02-01

Transplantation of neural stem cells (NSC) in diseased or injured brain tissue is widely studied as a potential treatment for various neurological pathologies. However, effective cell replacement therapy relies on the intrinsic capacity of cellular grafts to overcome hypoxic and/or immunological barriers after transplantation. In this context, it is hypothesized that structural support for grafted NSC will be of utmost importance. With this study, we present a novel decellularization protocol for 1.5 mm thick mouse brain sections, resulting in the generation of acellular three-dimensional (3D) brain sections. Next, the obtained 3D brain sections were seeded with murine NSC expressing both the eGFP and luciferase reporter proteins (NSC-eGFP/Luc). Using real-time bioluminescence imaging, the survival and growth of seeded NSC-eGFP/Luc cells was longitudinally monitored for 1-7 weeks in culture, indicating the ability of the acellular brain sections to support sustained ex vivo growth of NSC. Next, the organization of a 3D maze-like cellular structure was examined using confocal microscopy. Moreover, under mitogenic stimuli (EGF and hFGF-2), most cells in this 3D culture retained their NSC phenotype. Concluding, we here present a novel protocol for decellularization of mouse brain sections, which subsequently support long-term 3D culture of undifferentiated NSC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

PubMed Central

Daugherty, Ana M; Raz, Naftali

2015-01-01

Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology. PMID:26248580

Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

PubMed

Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

2015-08-01

Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body. © 2015 by The Author(s).

Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

PubMed

de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2018-01-01

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

Batch Immunostaining for Large-Scale Protein Detection in the Whole Monkey Brain

PubMed Central

Zangenehpour, Shahin; Burke, Mark W.; Chaudhuri, Avi; Ptito, Maurice

2009-01-01

Immunohistochemistry (IHC) is one of the most widely used laboratory techniques for the detection of target proteins in situ. Questions concerning the expression pattern of a target protein across the entire brain are relatively easy to answer when using IHC in small brains, such as those of rodents. However, answering the same questions in large and convoluted brains, such as those of primates presents a number of challenges. Here we present a systematic approach for immunodetection of target proteins in an adult monkey brain. This approach relies on the tissue embedding and sectioning methodology of NeuroScience Associates (NSA) as well as tools developed specifically for batch-staining of free-floating sections. It results in uniform staining of a set of sections which, at a particular interval, represents the entire brain. The resulting stained sections can be subjected to a wide variety of analytical procedures in order to measure protein levels, the population of neurons expressing a certain protein. PMID:19636291

A Proposal of New Reference System for the Standard Axial, Sagittal, Coronal Planes of Brain Based on the Serially-Sectioned Images

PubMed Central

Park, Jin Seo; Park, Hyo Seok; Shin, Dong Sun; Har, Dong-Hwan; Cho, Zang-Hee; Kim, Young-Bo; Han, Jae-Yong; Chi, Je-Geun

2010-01-01

Sectional anatomy of human brain is useful to examine the diseased brain as well as normal brain. However, intracerebral reference points for the axial, sagittal, and coronal planes of brain have not been standardized in anatomical sections or radiological images. We made 2,343 serially-sectioned images of a cadaver head with 0.1 mm intervals, 0.1 mm pixel size, and 48 bit color and obtained axial, sagittal, and coronal images based on the proposed reference system. This reference system consists of one principal reference point and two ancillary reference points. The two ancillary reference points are the anterior commissure and the posterior commissure. And the principal reference point is the midpoint of two ancillary reference points. It resides in the center of whole brain. From the principal reference point, Cartesian coordinate of x, y, z could be made to be the standard axial, sagittal, and coronal planes. PMID:20052359

Hollow Polypropylene Yarns as a Biomimetic Brain Phantom for the Validation of High-Definition Fiber Tractography Imaging.

PubMed

Guise, Catarina; Fernandes, Margarida M; Nóbrega, João M; Pathak, Sudhir; Schneider, Walter; Fangueiro, Raul

2016-11-09

Current brain imaging methods largely fail to provide detailed information about the location and severity of axonal injuries and do not anticipate recovery of the patients with traumatic brain injury. High-definition fiber tractography appears as a novel imaging modality based on water motion in the brain that allows for direct visualization and quantification of the degree of axons damage, thus predicting the functional deficits due to traumatic axonal injury and loss of cortical projections. This neuroimaging modality still faces major challenges because it lacks a "gold standard" for the technique validation and respective quality control. The present work aims to study the potential of hollow polypropylene yarns to mimic human white matter axons and construct a brain phantom for the calibration and validation of brain diffusion techniques based on magnetic resonance imaging, including high-definition fiber tractography imaging. Hollow multifilament polypropylene yarns were produced by melt-spinning process and characterized in terms of their physicochemical properties. Scanning electronic microscopy images of the filaments cross section has shown an inner diameter of approximately 12 μm, confirming their appropriateness to mimic the brain axons. The chemical purity of polypropylene yarns as well as the interaction between the water and the filament surface, important properties for predicting water behavior and diffusion inside the yarns, were also evaluated. Restricted and hindered water diffusion was confirmed by fluorescence microscopy. Finally, the yarns were magnetic resonance imaging scanned and analyzed using high-definition fiber tractography, revealing an excellent choice of these hollow polypropylene structures for simulation of the white matter brain axons and their suitability for constructing an accurate brain phantom.

Brain morphology in children with nevoid basal cell carcinoma syndrome.

PubMed

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

2017-04-01

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

Interpersonal relatedness and psychological functioning following traumatic brain injury: implications for marital and family therapists

PubMed Central

Bay, EH; Blow, AJ; Yan, XE

2015-01-01

Recovery from a mild to moderate traumatic brain injury (TBI) is a challenging process for injured persons and their families. Guided by attachment theory, we investigated whether relationship conflict, social support, or sense of belonging were associated with psychological functioning. Community-dwelling persons with TBI (N=75) and their relatives/significant others (N=74) were surveyed on relationship variables, functional status, and TBI symptom severity. Results from this cross-sectional study revealed that only sense of belonging was a significant predictor of post-injury psychological functioning, although interpersonal conflict approached significance. No relevant pre-injury or injury-related variables impacted these relationships, except marital status. Our findings suggest that interventions targeting strengthening the injured persons' sense of belonging and lowering interpersonal conflict may benefit those living with TBI. PMID:22804472

Interpersonal relatedness and psychological functioning following traumatic brain injury: implications for marital and family therapists.

PubMed

Bay, Esther H; Blow, Adrian J; Yan, Xie Emily

2012-07-01

Recovery from a mild-to-moderate traumatic brain injury (TBI) is a challenging process for injured persons and their families. Guided by attachment theory, we investigated whether relationship conflict, social support, or sense of belonging were associated with psychological functioning. Community-dwelling persons with TBI (N = 75) and their relatives/significant others (N = 74) were surveyed on relationship variables, functional status, and TBI symptom severity. Results from this cross-sectional study revealed that only sense of belonging was a significant predictor of postinjury psychological functioning, although interpersonal conflict approached significance. No relevant preinjury or injury-related variables impacted these relationships, except marital status. Our findings suggest that interventions targeting strengthening the injured persons' sense of belonging and lowering interpersonal conflict may benefit those living with TBI. © 2011 American Association for Marriage and Family Therapy.

The Golden Section as Optical Limitation.

PubMed

Elliott, Mark A; Kelly, Joy; Friedel, Jonas; Brodsky, Jennifer; Mulcahy, Paul

2015-01-01

The golden section, ϕ = (1 + √5)/2 = 1.618... and its companion ϕ = 1/ϕ = ϕ -1 = 0.618..., are irrational numbers which for centuries were believed to confer aesthetic appeal. In line with the presence of golden sectioning in natural growth patterns, recent EEG recordings show an absence of coherence between brain frequencies related by the golden ratio, suggesting the potential relevance of the golden section to brain dynamics. Using Mondrian-type patterns comprising a number of paired sections in a range of five section-section areal ratios (including golden-sectioned pairs), participants were asked to indicate as rapidly and accurately as possible the polarity (light or dark) of the smallest section in the patterns. They were also asked to independently assess the aesthetic appeal of the patterns. No preference was found for golden-sectioned patterns, while reaction times (RTs) tended to decrease overall with increasing ratio independently of each pattern's fractal dimensionality. (Fractal dimensionality was unrelated to ratio and measured in terms of the Minkowski-Bouligand box-counting dimension). The ease of detecting the smallest section also decreased with increasing ratio, although RTs were found to be substantially slower for golden-sectioned patterns under 8-paired sectioned conditions. This was confirmed by a significant linear relationship between RT and ratio (p < .001) only when the golden-sectioned RTs were excluded [the relationship was non-significant for the full complement of ratios (p = .217)]. Image analysis revealed an absence of spatial frequencies between 4 and 8 cycles-per-degree that was exclusive to the 8-paired (golden)-sectioned patterns. The significance of this was demonstrated in a subsequent experiment by addition of uniformly distributed random noise to the patterns. This provided a uniform spatial-frequency profile for all patterns, which did not influence the decrease in RT with increasing ratio but abolished the elevated RTs to golden-sectioned patterns. This suggests that optical limitation in the form of reduced inter-neural synchronization during spatial-frequency coding may be the foundation for the perceptual effects of golden sectioning.

A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing.

PubMed

Murakami, Tatsuya C; Mano, Tomoyuki; Saikawa, Shu; Horiguchi, Shuhei A; Shigeta, Daichi; Baba, Kousuke; Sekiya, Hiroshi; Shimizu, Yoshihiro; Tanaka, Kenji F; Kiyonari, Hiroshi; Iino, Masamitsu; Mochizuki, Hideki; Tainaka, Kazuki; Ueda, Hiroki R

2018-04-01

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature.

PubMed

Hosono-Fukao, Tomomi; Ohtake-Niimi, Shiori; Nishitsuji, Kazuchika; Hossain, Md Motarab; van Kuppevelt, Toin H; Michikawa, Makoto; Uchimura, Kenji

2011-11-01

RB4CD12 is a phage display antibody that recognizes a heparan sulfate (HS) glycosaminoglycan epitope. The epitope structure is proposed to contain a trisulfated disaccharide, [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-], which supports HS binding to various macromolecules such as growth factors and cytokines in central nervous tissues. Chemically modified heparins that lack the trisulfated disaccharides failed to inhibit the RB4CD12 recognition of HS chains. To determine the localization of the RB4CD12 anti-HS epitope in the brain, we performed an immunohistochemical analysis for cryocut sections of mouse brain. The RB4CD12 staining signals were colocalized with laminin and were detected abundantly in the vascular basement membrane. Bacterial heparinases eliminated the RB4CD12 staining signals. The RB4CD12 epitope localization was confirmed by immunoelectron microscopy. Western blotting analysis revealed that the size of a major RB4CD12-positive molecule is ∼460 kDa in a vessel-enriched fraction of the mouse brain. Disaccharide analysis with reversed-phase ion-pair HPLC showed that [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-] trisulfated disaccharide residues are present in HS purified from the vessel-enriched brain fraction. These results indicated that the RB4CD12 anti-HS epitope exists in large quantities in the brain vascular basement membrane. Copyright © 2011 Wiley-Liss, Inc.

Interaction between LSD and dopamine D2/3 binding sites in pig brain.

PubMed

Minuzzi, Luciano; Nomikos, George G; Wade, Mark R; Jensen, Svend B; Olsen, Aage K; Cumming, Paul

2005-06-15

The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD. (c) 2005 Wiley-Liss, Inc.

Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry.

PubMed

Henderson, Fiona; Hart, Philippa J; Pradillo, Jesus M; Kassiou, Michael; Christie, Lidan; Williams, Kaye J; Boutin, Herve; McMahon, Adam

2018-05-15

Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In vivo positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex vivo tool for brain recovery imaging. Magnetic resonance imaging (MRI) was used to image a rat brain 48 h after ischaemic stroke to locate the infarcted regions of the brain. PET was carried out 3 months post-stroke using the tracers [ 18 F]DPA-714 for TSPO and [ 18 F]IAM6067 for sigma-1 receptors to image neuroinflammation and neurodegeneration, respectively. The rat brain was flash-frozen immediately after PET scanning, and sectioned for matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging. Three months post-stroke, PET imaging shows minimal detection of neurodegeneration and neuroinflammation, indicating that the brain has stabilised. However, MALDI-MS images reveal distinct differences in lipid distributions (e.g. phosphatidylcholine and sphingomyelin) between the scar and the healthy brain, suggesting that recovery processes are still in play. It is currently not known if the altered lipids in the scar will change on a longer time scale, or if they are stabilised products of the brain post-stroke. The data demonstrates the ability to combine MALD-MS with in vivo PET to image different aspects of stroke recovery. Copyright © 2018 John Wiley & Sons, Ltd.

Antisera against Neisseria gonorrhoeae cross-react with specific brain proteins of the common marmoset monkey and other nonhuman primate species.

PubMed

Reuss, Bernhard; Asif, Abdul R; Almamy, Abdullah; Schwerk, Christian; Schroten, Horst; Ishikawa, Hiroshi; Drummer, Charis; Behr, Rüdiger

2016-12-15

Prenatal maternal infections with Neisseria gonorrhoeae (NG) correlate with an increased lifetime probability for the offspring to develop psychosis. We could previously demonstrate that in human choroid plexus papilloma cells, anti-NG antibodies (α-NG) bind to mitochondrial proteins HSP60 and ATPB, and interfere with cellular energy metabolism. To assess the in vivo relevance for this, especially during prenatal neural development, we investigated here interactions of NG-specific antisera (α-NG1, α-NG2) with brain, choroid plexus and other non-neural tissues in pre- and perinatal samples of the nonhuman primate (NHP) Callithrix jacchus (CJ), a NHP model for preclinical research. In histological sections at embryonic day E75, immunohistochemistry revealed α-NG1 and -2-staining in choroid plexus, ganglionic hill, optic cup, heart, and liver. Within the cells, organelle-like structures were labeled, which could be identified by immunohistochemical double-labeling as mitochondria. Both one- and two-dimensional Western blot analysis revealed tissue specific patterns of α-NG1 immunoreactive bands and spots, respectively, which were subsequently characterized by mass spectrometry. Thereby we could confirm the interactions of α-NG1 with human HSP60 and ATPB also in CJ choroid plexus and liver. Even more important, in the CJ brain, several new targets, including NCAM1, CRMP2, and SYT1, were identified, which by unrelated studies have been previously suggested to correlate with an increased schizophrenia risk. These findings support the idea that the marmoset monkey is a useful NHP model to investigate the role of maternal bacterial infections during prenatal brain development, and thereby might improve the understanding of this important aspect of schizophrenia pathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

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

Yang, SH.; Ballmann, C.; Quarles, C. A.

2009-03-10

The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixedmore » in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.« less

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

PubMed

Klein, H C; Krop-Van Gastel, W; Go, K G; Korf, J

1993-02-01

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

Structural differences in the brain between wild and laboratory rats (Rattus norvegicus): potential contribution to wariness.

PubMed

Koizumi, Ryoko; Kiyokawa, Yasushi; Mikami, Kaori; Ishii, Akiko; Tanaka, Kazuyuki D; Tanikawa, Tsutomu; Takeuchi, Yukari

2018-05-11

Wild animals typically exhibit defensive behaviors in response to a wider range and/or a weaker intensity of stimuli compared with domestic animals. However, little is known about the neural mechanisms underlying "wariness" in wild animals. Wild rats are one of the most accessible wild animals for experimental research. Laboratory rats are a domesticated form of wild rat, belonging to the same species, and are therefore considered suitable control animals for wild rats. Based on these factors, we analyzed structural differences in the brain between wild and laboratory rats to elucidate the neural mechanisms underlying wariness. We examined wild rats trapped in Tokyo, and weight-matched laboratory rats. We then prepared brain sections and compared the basolateral complex of the amygdala (BLA), the bed nucleus of the stria terminalis (BNST), the main olfactory bulb, and the accessory olfactory bulb. The results revealed that wild rats exhibited larger BLA, BNST and caudal part of the accessory olfactory bulb compared with laboratory rats. These results suggest that the BLA, BNST, and vomeronasal system potentially contribute to wariness in wild rats.

The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs.

PubMed

Falk, Dean; Lepore, Frederick E; Noe, Adrianne

2013-04-01

Upon his death in 1955, Albert Einstein's brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein's entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein's sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein's brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein's brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein's parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein's brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein's brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci.

Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

PubMed Central

Mueller, Karsten; Möller, Harald E.; Horstmann, Annette; Busse, Franziska; Lepsien, Jöran; Blüher, Matthias; Stumvoll, Michael; Villringer, Arno; Pleger, Burkhard

2015-01-01

Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM) and white matter (WM) that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging (MRI) together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training twice a week over a period of 3 months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI), reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C), and alterations of serum brain-derived neurotrophic factor (BDNF) concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing. PMID:26190989

The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs

PubMed Central

Lepore, Frederick E.; Noe, Adrianne

2013-01-01

Upon his death in 1955, Albert Einstein’s brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein’s entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein’s sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein’s brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein’s brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein’s parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein’s brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein’s brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci. PMID:23161163

Selected Gray Matter Volumes and Gender but Not Basal Ganglia nor Cerebellum Gyri Discriminate Left Versus Right Cerebral Hemispheres: Multivariate Analyses in human Brains at 3T.

PubMed

Roldan-Valadez, Ernesto; Suarez-May, Marcela A; Favila, Rafael; Aguilar-Castañeda, Erika; Rios, Camilo

2015-07-01

Interest in the lateralization of the human brain is evident through a multidisciplinary number of scientific studies. Understanding volumetric brain asymmetries allows the distinction between normal development stages and behavior, as well as brain diseases. We aimed to evaluate volumetric asymmetries in order to select the best gyri able to classify right- versus left cerebral hemispheres. A cross-sectional study performed in 47 right-handed young-adults healthy volunteers. SPM-based software performed brain segmentation, automatic labeling and volumetric analyses for 54 regions involving the cerebral lobes, basal ganglia and cerebellum from each cerebral hemisphere. Multivariate discriminant analysis (DA) allowed the assembling of a predictive model. DA revealed one discriminant function that significantly differentiated left vs. right cerebral hemispheres: Wilks' λ = 0.008, χ(2) (9) = 238.837, P < 0.001. The model explained 99.20% of the variation in the grouping variable and depicted an overall predictive accuracy of 98.8%. With the influence of gender; the selected gyri able to discriminate between hemispheres were middle orbital frontal gyrus (g.), angular g., supramarginal g., middle cingulum g., inferior orbital frontal g., calcarine g., inferior parietal lobule and the pars triangularis inferior frontal g. Specific brain gyri are able to accurately classify left vs. right cerebral hemispheres by using a multivariate approach; the selected regions correspond to key brain areas involved in attention, internal thought, vision and language; our findings favored the concept that lateralization has been evolutionary favored by mental processes increasing cognitive efficiency and brain capacity. © 2015 Wiley Periodicals, Inc.

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.

Brain-to-Brain Synchrony Tracks Real-World Dynamic Group Interactions in the Classroom.

PubMed

Dikker, Suzanne; Wan, Lu; Davidesco, Ido; Kaggen, Lisa; Oostrik, Matthias; McClintock, James; Rowland, Jess; Michalareas, Georgios; Van Bavel, Jay J; Ding, Mingzhou; Poeppel, David

2017-05-08

The human brain has evolved for group living [1]. Yet we know so little about how it supports dynamic group interactions that the study of real-world social exchanges has been dubbed the "dark matter of social neuroscience" [2]. Recently, various studies have begun to approach this question by comparing brain responses of multiple individuals during a variety of (semi-naturalistic) tasks [3-15]. These experiments reveal how stimulus properties [13], individual differences [14], and contextual factors [15] may underpin similarities and differences in neural activity across people. However, most studies to date suffer from various limitations: they often lack direct face-to-face interaction between participants, are typically limited to dyads, do not investigate social dynamics across time, and, crucially, they rarely study social behavior under naturalistic circumstances. Here we extend such experimentation drastically, beyond dyads and beyond laboratory walls, to identify neural markers of group engagement during dynamic real-world group interactions. We used portable electroencephalogram (EEG) to simultaneously record brain activity from a class of 12 high school students over the course of a semester (11 classes) during regular classroom activities (Figures 1A-1C; Supplemental Experimental Procedures, section S1). A novel analysis technique to assess group-based neural coherence demonstrates that the extent to which brain activity is synchronized across students predicts both student class engagement and social dynamics. This suggests that brain-to-brain synchrony is a possible neural marker for dynamic social interactions, likely driven by shared attention mechanisms. This study validates a promising new method to investigate the neuroscience of group interactions in ecologically natural settings. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Anomalous single-subject based morphological cortical networks in drug-naive, first-episode major depressive disorder.

PubMed

Chen, Taolin; Kendrick, Keith M; Wang, Jinhui; Wu, Min; Li, Kaiming; Huang, Xiaoqi; Luo, Yuejia; Lui, Su; Sweeney, John A; Gong, Qiyong

2017-05-01

Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group-level data. Such disruptions have not yet been identified in single-patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross-sectional structural brain network study of 33 treatment-naive, first-episode MDD patients and 33 age-, gender-, and education-matched healthy controls (HCs). Weighted graph-theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole-brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default-mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex-striatum-thalamus-cerebellum and thalamo-hippocampal circuitry. MDD-related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment-naive, first episode MDD patients. Circuit-specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38:2482-2494, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

Determining Optimal Microwave Antigen Retrieval Conditions for Microtubule-Associated Protein 2 Immunohistochemistry in the Guinea Pig Brain

DTIC Science & Technology

2002-12-01

sections of formalin-fixed guinea pig brains using different MAP-2 monoclonal antibodies. Brain sections were boiled in sodium citrate, citric acid...citric acid solution at pH 6.0 is the optimal microwave-assisted AR method for immunolabeling MAP-2 in formalin-fixed, paraffin-processed guinea pig brain...studies on archival guinea pig brain paraffin blocks, ultimately relaxing the use of additional animals to evaluate changes in MAP-2 expression between chemical warfare nerve agent-treated and control samples.

Double activity imaging reveals distinct cellular targets of haloperidol, clozapine and dopamine D(3) receptor selective RGH-1756.

PubMed

Kovács, K J; Csejtei, M; Laszlovszky, I

2001-03-01

Acute administration of typical (haloperidol) and atypical (clozapine) antipsychotics results in distinct and overlapping regions of immediate-early gene expression in the rat brain. RGH-1756 is a recently developed atypical antipsychotic with high affinity to dopamine D(3) receptors that results in a unique pattern of c-Fos induction. A single injection of either antipsychotic results in c-fos mRNA expression that peaks around 30 min after drug administration, while the maximum of c-Fos protein induction is seen 2 h after challenge. The transient and distinct temporal inducibility of c-fos mRNA and c-Fos protein was exploited to reveal and compare cellular targets of different antipsychotic drugs by concomitant localization of c-fos mRNA and c-Fos immunoreactivity in brain sections of rats that were timely challenged with two different antipsychotics. Double activity imaging revealed that haloperidol, clozapine and RGH-1756 share cellular targets in the nucleus accumbens, where 40% of all labeled neurons displayed both c-fos mRNA and c-Fos protein. Haloperidol activates cells in the caudate putamen, while clozapine-responsive, single labeled neurons were dominant in the prefrontal cortex and major island of Calleja. RGH-1756 targets haloperidol-sensitive cells in the caudate putamen, but cells that are activated by clozapine and RGH-1756 in the major island of Calleja are different.

In Vivo Fiber-Optic Raman Mapping Of Metastases In Mouse Brains

NASA Astrophysics Data System (ADS)

Stelling, A.; Kirsch, M.; Steiner, G.; Krafft, C.; Schackert, G.; Salzer, R.

2010-08-01

Vibrational spectroscopy, in particular Raman spectroscopy, has potential applications in the field of in vivo diagnostics. Raman and FT-IR spectroscopy analyze the complete biochemical information at any given pixel within the visual field. Here we demonstrate the feasibility of performing Raman spectroscopic measurements on living mice brains using a fiber-optic probe with a nominal spatial resolution of 60 μm. The objectives of this study were to 1) evaluate preclinical models, namely murine brain slices containing experimental tumors, 2) optimize the preparation of pristine brain tissue to obtain reference information, to 3) optimize the conditions for introducing a fiber-optic probe to acquire Raman maps in vivo, and 4) to transfer results obtained from human brain tumors to an animal model. Disseminated brain metastases of malignant melanomas were induced by injecting tumor cells into the carotid artery of mice. The procedure mimicked hematogenous tumor spread in one brain hemisphere while the other hemisphere remained tumor free. Three series of sections were prepared consecutively from whole mouse brains: pristine, 2-mm thick sections for Raman mapping and dried, thin sections for FT-IR imaging, hematoxylin and eosin-stained thin sections for histopathological assessment. Raman maps were collected serially using a spectrometer coupled to a fiber-optic probe. FT-IR images were recorded using a spectrometer with a multi-channel detector. The FT-IR images and the Raman maps were evaluated by multivariate data analysis. The results obtained from the thin section studies were employed to guide measurements of murine brains in vivo. Raman maps with an acquisition time of over an hour could be performed on the living animals. No damage to the tissue was observed.

Toward an operational model of decision making, emotional regulation, and mental health impact.

PubMed

Collura, Thomas Francis; Zalaquett, Ronald P; Bonnstetter, Carlos Joyce; Chatters, Seria J

2014-01-01

Current brain research increasingly reveals the underlying mechanisms and processes of human behavior, cognition, and emotion. In addition to being of interest to a wide range of scientists, educators, and professionals, as well as laypeople, brain-based models are of particular value in a clinical setting. Psychiatrists, psychologists, counselors, and other mental health professionals are in need of operational models that integrate recent findings in the physical, cognitive, and emotional domains, and offer a common language for interdisciplinary understanding and communication. Based on individual traits, predispositions, and responses to stimuli, we can begin to identify emotional and behavioral pathways and mental processing patterns. The purpose of this article is to present a brain-path activation model to understand individual differences in decision making and psychopathology. The first section discusses the role of frontal lobe electroencephalography (EEG) asymmetry, summarizes state- and trait-based models of decision making, and provides a more complex analysis that supplements the traditional simple left-right brain model. Key components of the new model are the introduction of right hemisphere parallel and left hemisphere serial scanning in rendering decisions, and the proposition of pathways that incorporate both past experiences as well as future implications into the decision process. Main attributes of each decision-making mechanism are provided. The second section applies the model within the realm of clinical mental health as a tool to understand specific human behavior and pathology. Applications include general and chronic anxiety, depression, paranoia, risk taking, and the pathways employed when well-functioning operational integration is observed. Finally, specific applications such as meditation and mindfulness are offered to facilitate positive functioning.

Microbleeds in postmortem brains of patients with Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study.

PubMed

De Reuck, Jacques L; Cordonnier, Charlotte; Deramecourt, Vincent; Auger, Florent; Durieux, Nicolas; Bordet, Regis; Maurage, Claude-Alain; Leys, Didier; Pasquier, Florence

2013-01-01

This study aims to determine the distribution and to quantify microbleeds (MBs) in postmortem brains of patients with Alzheimer disease (AD) on T2*-weighted gradient-echo 7.0 T magnetic resonance imaging. Twenty-eight AD brains were compared with 5 controls. The AD brains were subdivided further: 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central, and the occipital level of a cerebral hemisphere. MBs prevailed in the central sections (P=0.005) of AD brains without CAA, whereas in AD-CAA brains, they were more frequent in all coronal sections (P≤0.002). They prevailed in the deep cortical layers of the AD brains and of the controls (P≤0.03). They were significantly increased in all cortical layers of the AD-CAA brains (P≤0.04), compared with the controls. MBs prevalence in brains of AD patients had a different topographic distribution according to the absence or presence of severe CAA.

In Silico Prediction and Validation of Gfap as an miR-3099 Target in Mouse Brain.

PubMed

Abidin, Shahidee Zainal; Leong, Jia-Wen; Mahmoudi, Marzieh; Nordin, Norshariza; Abdullah, Syahril; Cheah, Pike-See; Ling, King-Hwa

2017-08-01

MicroRNAs are small non-coding RNAs that play crucial roles in the regulation of gene expression and protein synthesis during brain development. MiR-3099 is highly expressed throughout embryogenesis, especially in the developing central nervous system. Moreover, miR-3099 is also expressed at a higher level in differentiating neurons in vitro, suggesting that it is a potential regulator during neuronal cell development. This study aimed to predict the target genes of miR-3099 via in-silico analysis using four independent prediction algorithms (miRDB, miRanda, TargetScan, and DIANA-micro-T-CDS) with emphasis on target genes related to brain development and function. Based on the analysis, a total of 3,174 miR-3099 target genes were predicted. Those predicted by at least three algorithms (324 genes) were subjected to DAVID bioinformatics analysis to understand their overall functional themes and representation. The analysis revealed that nearly 70% of the target genes were expressed in the nervous system and a significant proportion were associated with transcriptional regulation and protein ubiquitination mechanisms. Comparison of in situ hybridization (ISH) expression patterns of miR-3099 in both published and in-house-generated ISH sections with the ISH sections of target genes from the Allen Brain Atlas identified 7 target genes (Dnmt3a, Gabpa, Gfap, Itga4, Lxn, Smad7, and Tbx18) having expression patterns complementary to miR-3099 in the developing and adult mouse brain samples. Of these, we validated Gfap as a direct downstream target of miR-3099 using the luciferase reporter gene system. In conclusion, we report the successful prediction and validation of Gfap as an miR-3099 target gene using a combination of bioinformatics resources with enrichment of annotations based on functional ontologies and a spatio-temporal expression dataset.

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach.

PubMed

Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

2015-01-01

Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

PubMed Central

Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

2015-01-01

Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research. PMID:26257697

Only Time Will Tell: Cross-Sectional Studies Offer No Solution to the Age-Brain-Cognition Triangle--Comment on Salthouse (2011)

ERIC Educational Resources Information Center

Raz, Naftali; Lindenberger, Ulman

2011-01-01

Salthouse (2011) critically reviewed cross-sectional and longitudinal relations among adult age, brain structure, and cognition (ABC) and identified problems in interpretation of the extant literature. His review, however, missed several important points. First, there is enough disparity among the measures of brain structure and cognitive…

Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

PubMed

Hanlon, C A; Dowdle, L T; Jones, J L

2016-01-01

Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). © 2016 Elsevier Inc. All rights reserved.

Short Nissl staining for incubated cryostat sections of the brain.

PubMed

Lindroos, O F

1991-01-01

Nissl stain often binds poorly to cryostat sections which have been incubated in solutions of radiolabeled ligands. Such incubation is used in receptor autoradiography of the brain when using the in vitro method. We have developed a rapid (16 min) modification of Nissl staining for sections that bind stain poorly, e.g., incubated sections. The method stains well sections which cannot be stained with other rapid Nissl staining methods.

Direct visualization of anatomic subfields within the superior aspect of the human lateral thalamus by MRI at 7T.

PubMed

Kanowski, M; Voges, J; Buentjen, L; Stadler, J; Heinze, H-J; Tempelmann, C

2014-09-01

The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. Inversion recovery-prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future. © 2014 by American Journal of Neuroradiology.

Sex beyond the genitalia: The human brain mosaic

PubMed Central

Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

2015-01-01

Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain. PMID:26621705

Comparison of a modified mid-coronal sectioning technique and Wilson's technique when conducting eye and brain examinations in rabbit teratology studies.

PubMed

Ziejewski, Mary K; Solomon, Howard M; Rendemonti, Joyce; Stanislaus, Dinesh

2015-02-01

There are two methods used when examining fetal rabbit eyes and brain in teratology studies. One method employs prior fixation before serial sectioning (Wilson's technique) and the other uses fresh tissue (mid-coronal sectioning). We modified the mid-coronal sectioning technique to include removal of eyes and brain for closer examination and to increase the number of structures that can be evaluated and compared it to the Wilson's technique. We found that external examination of the head, in conjunction with either sectioning method, is equally sensitive in identifying developmental defects. We evaluated 40,401 New Zealand White (NZW) and Dutch-Belted (DB) rabbit fetuses for external head alterations, of which 28,538 fetuses were further examined for eye and brain alterations using the modified mid-coronal sectioning method (16,675 fetuses) or Wilson's technique (11,863 fetuses). The fetuses were from vehicle control or drug-treated pregnant rabbits in embryo-fetal development studies conducted to meet international regulatory requirements for the development of new drugs. Both methods detected the more common alterations (microphthalmia and dilated lateral cerebral ventricles) and other less common findings (changes in size and/or shape of eye and brain structures). While both methods are equally sensitive at detecting common and rare developmental defects, the modified mid-coronal sectioning technique eliminates the use of chemicals and concomitant fixation artifacts that occur with the Wilson's technique and allows for examination of 100% intact fetuses thereby increasing potential for detecting eye and brain alterations as these findings occur infrequently in rabbits. © 2015 Wiley Periodicals, Inc.

Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

PubMed Central

Erickson, Michelle A.

2018-01-01

Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of the brain, and are also important regulators of neuroimmune communication. It is increasingly appreciated that communication between the brain and immune system contributes to physiologic processes, adaptive responses, and disease states. In this review, we discuss the highly specialized features of brain barriers that regulate neuroimmune communication in health and disease. In section I, we discuss the concept of immune privilege, provide working definitions of brain barriers, and outline the historical work that contributed to the understanding of CNS barrier functions. In section II, we discuss the unique anatomic, cellular, and molecular characteristics of the vascular blood–brain barrier (BBB), blood–cerebrospinal fluid barrier, and tanycytic barriers that confer their functions as neuroimmune interfaces. In section III, we consider BBB-mediated neuroimmune functions and interactions categorized as five neuroimmune axes: disruption, responses to immune stimuli, uptake and transport of immunoactive substances, immune cell trafficking, and secretions of immunoactive substances. In section IV, we discuss neuroimmune functions of CNS barriers in physiologic and disease states, as well as pharmacological interventions for CNS diseases. Throughout this review, we highlight many recent advances that have contributed to the modern understanding of CNS barriers and their interface functions. PMID:29496890

Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

PubMed Central

Palm, Christoph; Axer, Markus; Gräßel, David; Dammers, Jürgen; Lindemeyer, Johannes; Zilles, Karl; Pietrzyk, Uwe; Amunts, Katrin

2009-01-01

Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography. PMID:20461231

A new approach of light microscopic immunohistochemical triple-staining: combination of Fos labeling with diaminobenzidine-nickel and neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes.

PubMed

Majercikova, Z; Weering, H van; Scsukova, S; Mikkelsen, J D; Kiss, A

2012-10-01

The aim of the present study was to introduce a new approach of the light microscopic immunohistochemical triple-staining enabling to study the differences in the activity of at least two different phenotypes of neurons on the same histological section. For this purpose combination of Fos (a product of the immediate early gene) labeling with nickel intensified diaminobenzidine (DAB-Ni) and two neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes on cryo-processed 35-40 µm thick free-floating brain sections was selected. The parallel occurrence of three antibodies studied, i.e. Fos, hypocretin (HCRT), and melanin-concentrating hormone (MCH), was studied by a new methodic approach utilizing combination of Fos immunolabeled with DAB-Ni and HCRT and MCH labeled with Alexa488 and Alexa555 fluorescent dyes, respectively. Fos stimulation was induced by a single immobilization (IM0) for 120 min. Then, the rats were sacrificed, the brains removed, soaked with 30% sucrose in 0.1 M phosphate buffer (PB), cryo-sectioned throughout the hypothalamus into 35-40 μm thick coronal sections, collected, and washed in the same buffer for 10-15 min. Fos was revealed by avidin-biotin-peroxidase (ABC) complex and visualized by diaminobenzidine chromogen containing nickel chloride salt. HCRT and MCH neurons were visualized by the above mentioned fluorescent dyes. Evaluation of the Fos and fluorescent staining was performed in the computerized Axo Imager Carl Zeiss microscope using light and fluorescent illuminations. All the antibodies used showed clear immunoreactive staining. Fos staining occurred in the form of black color located in the cell nuclei. HCRH and MCH neuropeptides showed clear green and red fluorescence in the cell perikarya, respectively. The final merged picture showed Fos protein in the activated green HCRT or red MCH neurons in the form of white nuclei. The present study clearly demonstrate that the combination of Fos labeling with DAB-Ni and neuropeptides labeled with Alexa488 and Alexa555 on cryo-processed 35-40 µm thick free-floating brain sections is an excellent approach providing further advantages for quick and reproducible triple immuno-staining enabling to compare the activity of at least two phenotypes of neurons on the same section. Alexa488 and Alexa555 fluorescent dyes, Fos, hypocretin, melanin-concentrating hormone, cryostat sections, triple labeling immunohistochemistry, rat.

Quantifying Mesoscale Neuroanatomy Using X-Ray Microtomography

PubMed Central

Gray Roncal, William; Prasad, Judy A.; Fernandes, Hugo L.; Gürsoy, Doga; De Andrade, Vincent; Fezzaa, Kamel; Xiao, Xianghui; Vogelstein, Joshua T.; Jacobsen, Chris; Körding, Konrad P.

2017-01-01

Methods for resolving the three-dimensional (3D) microstructure of the brain typically start by thinly slicing and staining the brain, followed by imaging numerous individual sections with visible light photons or electrons. In contrast, X-rays can be used to image thick samples, providing a rapid approach for producing large 3D brain maps without sectioning. Here we demonstrate the use of synchrotron X-ray microtomography (µCT) for producing mesoscale (∼1 µm 3 resolution) brain maps from millimeter-scale volumes of mouse brain. We introduce a pipeline for µCT-based brain mapping that develops and integrates methods for sample preparation, imaging, and automated segmentation of cells, blood vessels, and myelinated axons, in addition to statistical analyses of these brain structures. Our results demonstrate that X-ray tomography achieves rapid quantification of large brain volumes, complementing other brain mapping and connectomics efforts. PMID:29085899

Combination of metallic impregnation and autoradiography of brain sections. A method for differentiation of proliferating glial cells in the brain of adult rats and mice.

PubMed

Korr, H

1978-12-29

After labeling with 14C-thymidine, frozen sections or paraffin sections of the brain of adult mice or rats were first stained by metallic impregnation and then coated with chrome alum gelatine and with an emulsion layer of about 10 micron. On the autoradiographs 14C-tracks are readily recognized above labelled astrocytes or oligodendrocytes, and these can be well discriminated, if the sections are processed by the silver carbonate method of Rio-Hortega. In contrast, no labelling is obtained, if the gold chloride sublimate method of Cajal is applied.

Hoyeraal-Hreidarsson syndrome: magnetic resonance imaging findings.

PubMed

Kuwashima, Shigeko

2009-10-01

Hoyeraal-Hreidarsson syndrome (HH) has been defined as a severe variant of dyskeratosis congenita (DKC). We report here a case of a 6-year-old girl with HH who presented with bone marrow hypoplasia, skin pigmentation, nail dystrophy, growth retardation, and bilateral retinal hemorrhage. Brain MRI revealed cerebellar hypoplasia, hypoplasia of the corpus callosum, a small pituitary gland, a small brain stem, and focal long T2 lesions in the thalamus and brain stem. A brain computed tomography scan revealed intracranial calcification as well. To the best of our knowledge, a small pituitary gland and focal long T2 lesions in the thalamus and brain stem have never been reported as a feature of HH.

A method for acetylcholinesterase staining of brain sections previously processed for receptor autoradiography.

PubMed

Lim, M M; Hammock, E A D; Young, L J

2004-02-01

Receptor autoradiography using selective radiolabeled ligands allows visualization of brain receptor distribution and density on film. The resolution of specific brain regions on the film often can be difficult to discern owing to the general spread of the radioactive label and the lack of neuroanatomical landmarks on film. Receptor binding is a chemically harsh protocol that can render the tissue virtually unstainable by Nissl and other conventional stains used to delineate neuroanatomical boundaries of brain regions. We describe a method for acetylcholinesterase (AChE) staining of slides previously processed for receptor binding. AChE staining is a useful tool for delineating major brain nuclei and tracts. AChE staining on sections that have been processed for receptor autoradiography provides a direct comparison of brain regions for more precise neuroanatomical description. We report a detailed thiocholine protocol that is a modification of the Koelle-Friedenwald method to amplify the AChE signal in brain sections previously processed for autoradiography. We also describe several temporal and experimental factors that can affect the density and clarity of the AChE signal when using this protocol.

Mapping of neuron soma size as an effective approach to delineate differences between neural populations.

PubMed

Lingley, Alexander J; Bowdridge, Joshua C; Farivar, Reza; Duffy, Kevin R

2018-04-30

A single histological marker applied to a slice of tissue often reveals myriad cytoarchitectonic characteristics that can obscure differences between neuron populations targeted for study. Isolation and measurement of a single feature from the tissue is possible through a variety of approaches, however, visualizing the data numerically or through graphs alone can preclude being able to identify important features and effects that are not obvious from direct observation of the tissue. We demonstrate an efficient, effective, and robust approach to quantify and visualize cytoarchitectural features in histologically prepared brain sections. We demonstrate that this approach is able to reveal small differences between populations of neurons that might otherwise have gone undiscovered. We used stereological methods to record the cross-sectional soma area and in situ position of neurons within sections of the cat, monkey, and human visual system. The two-dimensional coordinate of every measured cell was used to produce a scatter plot that recapitulated the natural spatial distribution of cells, and each point in the plot was color-coded according to its respective soma area. The final graphic display was a multi-dimensional map of neuron soma size that revealed subtle differences across neuron aggregations, permitted delineation of regional boundaries, and identified small differences between populations of neurons modified by a period of sensory deprivation. This approach to collecting and displaying cytoarchitectonic data is simple, efficient, and provides a means of investigating small differences between neuron populations. Copyright © 2018. Published by Elsevier B.V.

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

PubMed Central

Newson, Penny; Lynch-Frame, Ann; Roach, Rebecca; Bennett, Sarah; Carr, Vaughan; Chahl, Loris A

2005-01-01

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. PMID:16041396

Non-imaged based method for matching brains in a common anatomical space for cellular imagery.

PubMed

Midroit, Maëllie; Thevenet, Marc; Fournel, Arnaud; Sacquet, Joelle; Bensafi, Moustafa; Breton, Marine; Chalençon, Laura; Cavelius, Matthias; Didier, Anne; Mandairon, Nathalie

2018-04-22

Cellular imagery using histology sections is one of the most common techniques used in Neuroscience. However, this inescapable technique has severe limitations due to the need to delineate regions of interest on each brain, which is time consuming and variable across experimenters. We developed algorithms based on a vectors field elastic registration allowing fast, automatic realignment of experimental brain sections and associated labeling in a brain atlas with high accuracy and in a streamlined way. Thereby, brain areas of interest can be finely identified without outlining them and different experimental groups can be easily analyzed using conventional tools. This method directly readjusts labeling in the brain atlas without any intermediate manipulation of images. We mapped the expression of cFos, in the mouse brain (C57Bl/6J) after olfactory stimulation or a non-stimulated control condition and found an increased density of cFos-positive cells in the primary olfactory cortex but not in non-olfactory areas of the odor-stimulated animals compared to the controls. Existing methods of matching are based on image registration which often requires expensive material (two-photon tomography mapping or imaging with iDISCO) or are less accurate since they are based on mutual information contained in the images. Our new method is non-imaged based and relies only on the positions of detected labeling and the external contours of sections. We thus provide a new method that permits automated matching of histology sections of experimental brains with a brain reference atlas. Copyright © 2018 Elsevier B.V. All rights reserved.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain.

PubMed

Pei, Minjuan; Matsuda, Ken-Ichi; Sakamoto, Hirotaka; Kawata, Mitsuhiro

2006-03-01

Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.

Brain MRI volumetry in a single patient with mild traumatic brain injury.

PubMed

Ross, David E; Castelvecchi, Cody; Ochs, Alfred L

2013-01-01

This letter to the editor describes the case of a 42 year old man with mild traumatic brain injury and multiple neuropsychiatric symptoms which persisted for a few years after the injury. Initial CT scans and MRI scans of the brain showed no signs of atrophy. Brain volume was measured using NeuroQuant®, an FDA-approved, commercially available software method. Volumetric cross-sectional (one point in time) analysis also showed no atrophy. However, volumetric longitudinal (two points in time) analysis showed progressive atrophy in several brain regions. This case illustrated in a single patient the principle discovered in multiple previous group studies, namely that the longitudinal design is more powerful than the cross-sectional design for finding atrophy in patients with traumatic brain injury.

The lateral prefrontal cortex mediates the hyperalgesic effects of negative cognitions in chronic pain patients.

PubMed

Loggia, Marco L; Berna, Chantal; Kim, Jieun; Cahalan, Christine M; Martel, Marc-Olivier; Gollub, Randy L; Wasan, Ajay D; Napadow, Vitaly; Edwards, Robert R

2015-08-01

Although high levels of negative affect and cognitions have been associated with greater pain sensitivity in chronic pain conditions, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation and 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing in fibromyalgia (FM) patients. Using functional magnetic resonance imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex. A bootstrapped mediation analysis revealed that pain-anticipatory activity in the lateral prefrontal cortex mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of the lateral prefrontal cortex in the pathophysiology of FM-related hyperalgesia and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well-validated measure of negative cognitions and psychological distress. This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neurofeedback-based techniques aimed at modifying patients' negative affect and cognitions toward pain. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

The iconographic brain. A critical philosophical inquiry into (the resistance of) the image

PubMed Central

De Vos, Jan

2014-01-01

The brain image plays a central role in contemporary image culture and, in turn, (co)constructs contemporary forms of subjectivity. The central aim of this paper is to probe the unmistakably potent interpellative power of brain images by delving into the power of imaging and the power of the image itself. This is not without relevance for the neurosciences, inasmuch as these do not take place in a vacuum; hence the importance of inquiring into the status of the image within scientific culture and science itself. I will mount a critical philosophical investigation of the brain qua image, focusing on the issue of mapping the mental onto the brain and how, in turn, the brain image plays a pivotal role in processes of subjectivation. Hereto, I draw upon Science & Technology Studies, juxtaposed with culture and ideology critique and theories of image culture. The first section sets out from Althusser's concept of interpellation, linking ideology to subjectivity. Doing so allows to spell out the central question of the paper: what could serve as the basis for a critical approach, or, where can a locus of resistance be found? In the second section, drawing predominantly on Baudrillard, I delve into the dimension of virtuality as this is opened up by brain image culture. This leads to the question of whether the digital brain must be opposed to old analog psychology: is it the psyche which resists? This issue is taken up in the third section which, ultimately, concludes that the psychological is not the requisite locus of resistance. The fourth section proceeds to delineate how the brain image is constructed from what I call the data-gaze (the claim that brain data are always already visual). In the final section, I discuss how an engagement with theories of iconology affords a critical understanding of the interpellative force of the brain image, which culminates in the somewhat unexpected claim that the sought after resistance lies in the very status of the image itself. PMID:24860480

Leveraging Clinical Imaging Archives for Radiomics: Reliability of Automated Methods for Brain Volume Measurement.

PubMed

Adduru, Viraj R; Michael, Andrew M; Helguera, Maria; Baum, Stefi A; Moore, Gregory J

2017-09-01

Purpose To validate the use of thick-section clinically acquired magnetic resonance (MR) imaging data for estimating total brain volume (TBV), gray matter (GM) volume (GMV), and white matter (WM) volume (WMV) by using three widely used automated toolboxes: SPM ( www.fil.ion.ucl.ac.uk/spm/ ), FreeSurfer ( surfer.nmr.mgh.harvard.edu ), and FSL (FMRIB software library; Oxford Centre for Functional MR Imaging of the Brain, Oxford, England, https://fsl.fmrib.ox.ac.uk/fsl ). Materials and Methods MR images from a clinical archive were used and data were deidentified. The three methods were applied to estimate brain volumes from thin-section research-quality brain MR images and routine thick-section clinical MR images acquired from the same 38 patients (age range, 1-71 years; mean age, 22 years; 11 women). By using these automated methods, TBV, GMV, and WMV were estimated. Thin- versus thick-section volume comparisons were made for each method by using intraclass correlation coefficients (ICCs). Results SPM exhibited excellent ICCs (0.97, 0.85, and 0.83 for TBV, GMV, and WMV, respectively). FSL exhibited ICCs of 0.69, 0.51, and 0.60 for TBV, GMV, and WMV, respectively, but they were lower than with SPM. FreeSurfer exhibited excellent ICC of 0.63 only for TBV. Application of SPM's voxel-based morphometry on the modulated images of thin-section images and interpolated thick-section images showed fair to excellent ICCs (0.37-0.98) for the majority of brain regions (88.47% [306924 of 346916 voxels] of WM and 80.35% [377 282 of 469 502 voxels] of GM). Conclusion Thick-section clinical-quality MR images can be reliably used for computing quantitative brain metrics such as TBV, GMV, and WMV by using SPM. © RSNA, 2017 Online supplemental material is available for this article.

Brain electromagnetic activity and lightning: potentially congruent scale-invariant quantitative properties

PubMed Central

Persinger, Michael A.

2012-01-01

The space-time characteristics of the axonal action potential are remarkably similar to the scaled equivalents of lightning. The energy and current densities from these transients within their respective volumes or cross-sectional areas are the same order of magnitude. Length–velocity ratios and temporal durations are nearly identical. There are similar chemical consequences such as the production of nitric oxide. Careful, quantitative examination of the characteristics of lightning may reveal analogous features of the action potential that could lead to a more accurate understanding of these powerful correlates of neurocognitive processes. PMID:22615688

Three-dimensional atlas of iron, copper, and zinc in the mouse cerebrum and brainstem.

PubMed

Hare, Dominic J; Lee, Jason K; Beavis, Alison D; van Gramberg, Amanda; George, Jessica; Adlard, Paul A; Finkelstein, David I; Doble, Philip A

2012-05-01

Atlases depicting molecular and functional features of the brain are becoming an integral part of modern neuroscience. In this study we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantitatively measure iron (Fe), copper (Cu), and zinc (Zn) levels in a serially sectioned C57BL/6 mouse brain (cerebrum and brainstem). Forty-six sections were analyzed in a single experiment of approximately 158 h in duration. We constructed a 46-plate reference atlas by aligning quantified images of metal distribution with corresponding coronal sections from the Allen Mouse Brain Reference Atlas. The 46 plates were also used to construct three-dimensional models of Fe, Cu, and Zn distribution. This atlas represents the first reconstruction of quantitative trace metal distribution through the brain by LA-ICPMS and will facilitate the study of trace metals in the brain and help to elucidate their role in neurobiology.

Normal feline brain: clinical anatomy using magnetic resonance imaging.

PubMed

Mogicato, G; Conchou, F; Layssol-Lamour, C; Raharison, F; Sautet, J

2012-04-01

The purpose of this study was to provide a clinical anatomy atlas of the feline brain using magnetic resonance imaging (MRI). Brains of twelve normal cats were imaged using a 1.5 T magnetic resonance unit and an inversion/recovery sequence (T1). Fourteen relevant MRI sections were chosen in transverse, dorsal, median and sagittal planes. Anatomic structures were identified and labelled using anatomical texts and Nomina Anatomica Veterinaria, sectioned specimen heads, and previously published articles. The MRI sections were stained according to the major embryological and anatomical subdivisions of the brain. The relevant anatomical structures seen on MRI will assist clinicians to better understand MR images and to relate this neuro-anatomy to clinical signs. © 2011 Blackwell Verlag GmbH.

Neuroanatomy: The added value of the Klingler method.

PubMed

Silva, Susana M; Andrade, José Paulo

2016-11-01

Undergraduate neuroanatomy students are usually not able to achieve a clear comprehension of the spatial relationships existing between the white matter fiber tracts in spite of numerous neuroanatomy textbooks, atlases and multimedia tools. The objective of this paper is to show the educational value of the application of the Klingler fiber dissection technique and the use of these dissections in the understanding of the three-dimensional intrinsic anatomy of the brain white matter for medical students. Four formalin-fixed brains were dissected using the Klingler methodology in order to reveal the inner anatomical organization of the brain white matter. The most important fiber systems were dissected and their relationships to the cerebral and cerebellar gray matter structures visualized. These dissections were used as a learning tool in teaching the brain white matter structural and topographical connectivity. The white matter fiber systems were presented to undergraduate medical students during a neuroanatomy course. They observed and manipulated the dissected specimens leading to a thorough understanding of the configuration and location of the white matter fiber tracts, and their relationships to the ventricular system and gray matter structures. Subsequently, students were asked to answer a survey concerning the importance of the utilization of this material in their understanding of the three-dimensional intrinsic anatomy of the brain white matter. The knowledge acquired with this technique, complemented by conventional formalin-fixed sections may improve the neuroanatomical knowledge and future retention of medical students. Copyright © 2016 Elsevier GmbH. All rights reserved.

Brain BLAQ: Post-hoc thick-section histochemistry for localizing optogenetic constructs in neurons and their distal terminals

PubMed Central

Kupferschmidt, David A.; Cody, Patrick A.; Lovinger, David M.; Davis, Margaret I.

2015-01-01

Optogenetic constructs have revolutionized modern neuroscience, but the ability to accurately and efficiently assess their expression in the brain and associate it with prior functional measures remains a challenge. High-resolution imaging of thick, fixed brain sections would make such post-hoc assessment and association possible; however, thick sections often display autofluorescence that limits their compatibility with fluorescence microscopy. We describe and evaluate a method we call “Brain BLAQ” (Block Lipids and Aldehyde Quench) to rapidly reduce autofluorescence in thick brain sections, enabling efficient axon-level imaging of neurons and their processes in conventional tissue preparations using standard epifluorescence microscopy. Following viral-mediated transduction of optogenetic constructs and fluorescent proteins in mouse cortical pyramidal and dopaminergic neurons, we used BLAQ to assess innervation patterns in the striatum, a region in which autofluorescence often obscures the imaging of fine neural processes. After BLAQ treatment of 250–350 μm-thick brain sections, axons and puncta of labeled afferents were visible throughout the striatum using a standard epifluorescence stereomicroscope. BLAQ histochemistry confirmed that motor cortex (M1) projections preferentially innervated the matrix component of lateral striatum, whereas medial prefrontal cortex projections terminated largely in dorsal striosomes and distinct nucleus accumbens subregions. Ventral tegmental area dopaminergic projections terminated in a similarly heterogeneous pattern within nucleus accumbens and ventral striatum. Using a minimal number of easily manipulated and visualized sections, and microscopes available in most neuroscience laboratories, BLAQ enables simple, high-resolution assessment of virally transduced optogenetic construct expression, and post-hoc association of this expression with molecular markers, physiology and behavior. PMID:25698938

Brain-Wide Maps of "Fos" Expression during Fear Learning and Recall

ERIC Educational Resources Information Center

Cho, Jin-Hyung; Rendall, Sam D.; Gray, Jesse M.

2017-01-01

"Fos" induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which "Fos" induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide…

Comparing three-dimensional serial optical coherence tomography histology to MRI imaging in the entire mouse brain

NASA Astrophysics Data System (ADS)

Castonguay, Alexandre; Lefebvre, Joël; Pouliot, Philippe; Lesage, Frédéric

2018-01-01

An automated serial histology setup combining optical coherence tomography (OCT) imaging with vibratome sectioning was used to image eight wild type mouse brains. The datasets resulted in thousands of volumetric tiles resolved at a voxel size of (4.9×4.9×6.5) μm3 stitched back together to give a three-dimensional map of the brain from which a template OCT brain was obtained. To assess deformation caused by tissue sectioning, reconstruction algorithms, and fixation, OCT datasets were compared to both in vivo and ex vivo magnetic resonance imaging (MRI) imaging. The OCT brain template yielded a highly detailed map of the brain structure, with a high contrast in white matter fiber bundles and was highly resemblant to the in vivo MRI template. Brain labeling using the Allen brain framework showed little variation in regional brain volume among imaging modalities with no statistical differences. The high correspondence between the OCT template brain and its in vivo counterpart demonstrates the potential of whole brain histology to validate in vivo imaging.

Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1.

PubMed

Duarte, João V; Ribeiro, Maria J; Violante, Inês R; Cunha, Gil; Silva, Eduardo; Castelo-Branco, Miguel

2014-01-01

Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model-driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data-driven classification approach. We used support vector machines (SVM) to classify whole-brain GM and WM segments of structural T1 -weighted MRI scans from 39 participants with NF1 and 60 non-affected individuals, divided in children/adolescents and adults groups. We also employed voxel-based morphometry (VBM) as a univariate gold standard to study brain structural differences. SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%) revealing the existence of brain structural anomalies that discriminate NF1 individuals from controls. Accordingly, VBM analysis revealed structural differences in agreement with the SVM weight maps representing the most relevant brain regions for group discrimination. These included the hippocampus, basal ganglia, thalamus, and visual cortex. This multivariate data-driven analysis thus identified subtle anomalies in brain structure in the absence of visible pathology. Our results provide further insight into the neuroanatomical correlates of known features of the cognitive phenotype of NF1. Copyright © 2012 Wiley Periodicals, Inc.

Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke.

PubMed

Kim, Joonki; Kang, Sung-Wook; Mallilankaraman, Karthik; Baik, Sang-Ha; Lim, James C; Balaganapathy, Priyanka; She, David T; Lok, Ker-Zhing; Fann, David Y; Thambiayah, Uma; Tang, Sung-Chun; Stranahan, Alexis M; Dheen, S Thameem; Gelderblom, Mathias; Seet, Raymond C; Karamyan, Vardan T; Vemuganti, Raghu; Sobey, Christopher G; Mattson, Mark P; Jo, Dong-Gyu; Arumugam, Thiruma V

2018-05-01

Genetic changes due to dietary intervention in the form of either calorie restriction (CR) or intermittent fasting (IF) are not reported in detail until now. However, it is well established that both CR and IF extend the lifespan and protect against neurodegenerative diseases and stroke. The current research aims were first to describe the transcriptomic changes in brains of IF mice and, second, to determine whether IF induces extensive transcriptomic changes following ischemic stroke to protect the brain from injury. Mice were randomly assigned to ad libitum feeding (AL), 12 (IF12) or 16 (IF16) h daily fasting. Each diet group was then subjected to sham surgery or middle cerebral artery occlusion and consecutive reperfusion. Mid-coronal sections of ipsilateral cerebral tissue were harvested at the end of the 1 h ischemic period or at 3, 12, 24 or 72 h of reperfusion, and genome-wide mRNA expression was quantified by RNA sequencing. The cerebral transcriptome of mice in AL group exhibited robust, sustained up-regulation of detrimental genetic pathways under ischemic stroke, but activation of these pathways was suppressed in IF16 group. Interestingly, the cerebral transcriptome of AL mice was largely unchanged during the 1 h of ischemia, whereas mice in IF16 group exhibited extensive up-regulation of genetic pathways involved in neuroplasticity and down-regulation of protein synthesis. Our data provide a genetic molecular framework for understanding how IF protects brain cells against damage caused by ischemic stroke, and reveal cellular signaling and bioenergetic pathways to target in the development of clinical interventions.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate.

PubMed

Sharma, Suvasini; Sankhyan, Naveen; Kumar, Atin; Scheper, Gert C; van der Knaap, Marjo S; Gulati, Sheffali

2011-06-01

A 17-year-old Indian boy with gradually progressive ataxia with onset at 12 years of age is described. Magnetic resonance imaging (MRI) of the brain revealed extensive, inhomogeneous signal abnormalities in the cerebral white matter, with involvement of selected tracts in the brain stem and spinal cord. The imaging findings were characteristic of leukoencephalopathy with brain stem and spinal cord involvement and high lactate, a recently described leukodystrophy. Interestingly, magnetic resonance spectroscopy of the abnormal white matter did not reveal elevated lactate. The patient was compound heterozygous for 2 new mutations in DARS2, genetically confirming the diagnosis.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1992--December 31, 1992

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Brain Science of Ethics: Present Status and the Future

ERIC Educational Resources Information Center

Aoki, Ryuta; Funane, Tsukasa; Koizumi, Hideaki

2010-01-01

Recent advances in technologies for neuroscientific research enable us to investigate the neurobiological substrates of the human ethical sense. This article introduces several findings in "the brain science of ethics" obtained through "brain-observation" and "brain-manipulation" approaches. Studies over the past decade have revealed that several…

Resting state functional connectivity: its physiological basis and application in neuropharmacology.

PubMed

Lu, Hanbing; Stein, Elliot A

2014-09-01

Brain structures do not work in isolation; they work in concert to produce sensory perception, motivation and behavior. Systems-level network activity can be investigated by resting state magnetic resonance imaging (rsMRI), an emerging neuroimaging technique that assesses the synchrony of the brain's ongoing spontaneous activity. Converging evidence reveals that rsMRI is able to consistently identify distinct spatiotemporal patterns of large-scale brain networks. Dysregulation within and between these networks has been implicated in a number of neurodegenerative and neuropsychiatric disorders, including Alzheimer's disease and drug addiction. Despite wide application of this approach in systems neuroscience, the physiological basis of these fluctuations remains incompletely understood. Here we review physiological studies in electrical, metabolic and hemodynamic fluctuations that are most pertinent to the rsMRI signal. We also review recent applications to neuropharmacology - specifically drug effects on resting state fluctuations. We speculate that the mechanisms governing spontaneous fluctuations in regional oxygenation availability likely give rise to the observed rsMRI signal. We conclude by identifying several open questions surrounding this technique. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Published by Elsevier Ltd.

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

PubMed Central

Ross, Emily J; Graham, Devon L; Money, Kelli M; Stanwood, Gregg D

2015-01-01

Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose–response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures. PMID:24938210

Astrocytes refine cortical connectivity at dendritic spines

PubMed Central

Risher, W Christopher; Patel, Sagar; Kim, Il Hwan; Uezu, Akiyoshi; Bhagat, Srishti; Wilton, Daniel K; Pilaz, Louis-Jan; Singh Alvarado, Jonnathan; Calhan, Osman Y; Silver, Debra L; Stevens, Beth; Calakos, Nicole; Soderling, Scott H; Eroglu, Cagla

2014-01-01

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.04047.001 PMID:25517933

Structural Covariance of the Default Network in Healthy and Pathological Aging

PubMed Central

Turner, Gary R.

2013-01-01

Significant progress has been made uncovering functional brain networks, yet little is known about the corresponding structural covariance networks. The default network's functional architecture has been shown to change over the course of healthy and pathological aging. We examined cross-sectional and longitudinal datasets to reveal the structural covariance of the human default network across the adult lifespan and through the progression of Alzheimer's disease (AD). We used a novel approach to identify the structural covariance of the default network and derive individual participant scores that reflect the covariance pattern in each brain image. A seed-based multivariate analysis was conducted on structural images in the cross-sectional OASIS (N = 414) and longitudinal Alzheimer's Disease Neuroimaging Initiative (N = 434) datasets. We reproduced the distributed topology of the default network, based on a posterior cingulate cortex seed, consistent with prior reports of this intrinsic connectivity network. Structural covariance of the default network scores declined in healthy and pathological aging. Decline was greatest in the AD cohort and in those who progressed from mild cognitive impairment to AD. Structural covariance of the default network scores were positively associated with general cognitive status, reduced in APOEε4 carriers versus noncarriers, and associated with CSF biomarkers of AD. These findings identify the structural covariance of the default network and characterize changes to the network's gray matter integrity across the lifespan and through the progression of AD. The findings provide evidence for the large-scale network model of neurodegenerative disease, in which neurodegeneration spreads through intrinsically connected brain networks in a disease specific manner. PMID:24048852

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

PubMed

Sawicki, Marcin; Sołek-Pastuszka, Joanna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Bohatyrewicz, Romuald

2018-05-04

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Intersubject synchronization of cortical activity during natural vision.

PubMed

Hasson, Uri; Nir, Yuval; Levy, Ifat; Fuhrmann, Galit; Malach, Rafael

2004-03-12

To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to "model" activity in another brain, we found a striking level of voxel-by-voxel synchronization between individuals, not only in primary and secondary visual and auditory areas but also in association cortices. The results reveal a surprising tendency of individual brains to "tick collectively" during natural vision. The intersubject synchronization consisted of a widespread cortical activation pattern correlated with emotionally arousing scenes and regionally selective components. The characteristics of these activations were revealed with the use of an open-ended "reverse-correlation" approach, which inverts the conventional analysis by letting the brain signals themselves "pick up" the optimal stimuli for each specialized cortical area.

Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

NASA Astrophysics Data System (ADS)

Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

2017-10-01

Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

Educating the Other Half: Implications of Left/Right Brain Research.

ERIC Educational Resources Information Center

Rubenzer, Ronald L.

The document looks at left/right brain research as it relates to learning styles and teaching styles, particularly in special education. An initial section on brain basics covers the history of brain research, methods of investigation, cerebral dominance, divisions of labor of the bifunctional brain, language and related functions, bilingualism,…

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

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

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.

1984-08-01

(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturationmore » curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.« less

Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

PubMed Central

Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

2015-01-01

With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

Health assessment of gasoline and fuel oxygenate vapors: Neurotoxicity evaluation

PubMed Central

O’Callaghan, James P.; Daughtrey, Wayne C.; Clark, Charles R.; Schreiner, Ceinwen A.; White, Russell

2016-01-01

Sprague–Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from “baseline gasoline” (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000 mg/mg3 and exposures were for 6 h/day, 5 days/week for 13 weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiple brain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration. PMID:24879970

The brain in time: insights from neuromagnetic recordings.

PubMed

Hari, Riitta; Parkkonen, Lauri; Nangini, Cathy

2010-03-01

The millisecond time resolution of magnetoencephalography (MEG) is instrumental for investigating the brain basis of sensory processing, motor planning, cognition, and social interaction. We review the basic principles, recent progress, and future potential of MEG in noninvasive tracking of human brain activity. Cortical activation sequences from tens to hundreds of milliseconds can be followed during, e.g., perception, motor action, imitation, and language processing by recording both spontaneous and evoked brain signals. Moreover, tagging of sensory input can be used to reveal neuronal mechanisms of binaural interaction and perception of ambiguous images. The results support the emerging ideas of multiple, hierarchically organized temporal scales in human brain function. Instrumentation and data analysis methods are rapidly progressing, enabling attempts to decode the four-dimensional spatiotemporal signal patterns to reveal correlates of behavior and mental contents.

From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

PubMed

Naumann, Eva A; Fitzgerald, James E; Dunn, Timothy W; Rihel, Jason; Sompolinsky, Haim; Engert, Florian

2016-11-03

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data. Copyright © 2016 Elsevier Inc. All rights reserved.

High-resolution MRI of cranial nerves in posterior fossa at 3.0 T.

PubMed

Guo, Zi-Yi; Chen, Jing; Liang, Qi-Zhou; Liao, Hai-Yan; Cheng, Qiong-Yue; Fu, Shui-Xi; Chen, Cai-Xiang; Yu, Dan

2013-02-01

To evaluate the influence of high-resolution imaging obtainable with the higher field strength of 3.0 T on the visualization of the brain nerves in the posterior fossa. In total, 20 nerves were investigated on MRI of 12 volunteers each and selected for comparison, respectively, with the FSE sequences with 5 mm and 2 mm section thicknesses and gradient recalled echo (GRE) sequences acquired with a 3.0-T scanner. The MR images were evaluated by three independent readers who rated image quality according to depiction of anatomic detail and contrast with use of a rating scale. In general, decrease of the slice thickness showed a significant increase in the detection of nerves as well as in the image quality characteristics. Comparing FSE and GRE imaging, the course of brain nerves and brainstem vessels was visualized best with use of the three-dimensional (3D) pulse sequence. The comparison revealed the clear advantage of a thin section. The increased resolution enabled immediate identification of all brainstem nerves. GRE sequence most distinctly and confidently depicted pertinent structures and enables 3D reconstruction to illustrate complex relations of the brainstem. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

A radiologic correlation with the basic functional neuroanatomy of the brain.

PubMed

Bilicka, Z; Liska, M; Bluska, P; Bilicky, J

2014-01-01

Primary cortical areas for motor, sensory and sensitive functions are localized in certain areas of the brain cortex. In clinical practice, cross sectional imaging (computer tomography and magnetic resonance) is wildy used for diagnostics purpose, treatment planning and follow up of the patients. Accurate orientation in brain structures is necessary for the evaluation of radiological images. There are numerable landmark signs, which can be used for precise identification of important brain structures. In this review article, the mostly used anatomical landmarks are described and shown on the cross sectional images (magnetic resonance imaging) (Fig. 14, Ref. 25).

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy.

PubMed

Thien, Ady; Han, Julian Xinguang; Kumar, Krishan; Ng, Yew Poh; Rao, Jai Prashanth; Ng, Wai Hoe; King, Nicolas Kon Kam

2018-02-01

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis. Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%. Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

Dissociable brain biomarkers of fluid intelligence.

PubMed

Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

2016-08-15

Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Optimization of Glial Fibrillary Acidic Protein Immunoreactivity in Formalin-fixed, Paraffin-Embedded Guinea Pig Brain Sections

DTIC Science & Technology

2003-09-01

fixed, paraffin-embedded guinea pig brain sections using a variety of commercially available GFAP antibody clones. Of the 7 clones tested for cross...determining neuropathological consequences in the guinea pig following exposure to chemical warfare nerve agent.

Neuropathology of Cervical Dystonia

PubMed Central

Prudente, C.N.; Pardo, C.A.; Xiao, J.; Hanfelt, J.; Hess, E.J.; LeDoux, M.S.; Jinnah, H.A.

2012-01-01

The aim of this study was to search for neuropathological changes in postmortem brain tissue of individuals with cervical dystonia (CD). Multiple regions of formalin-preserved brains were collected from patients with CD and controls and examined with an extensive battery of histopathological stains in a two-stage study design. In stage one, 4 CD brains underwent a broad screening neuropathological examination. In stage two, these 4 CD brains were combined with 2 additional CD brains, and the subjective findings were quantified and compared to 16 age-matched controls. The initial subjective neuropathological assessment revealed only two regions with relatively consistent changes. The substantia nigra had frequent ubiquitin-positive intranuclear inclusions known as Marinesco bodies. Additionally, the cerebellum showed patchy loss of Purkinje cells, areas of focal gliosis and torpedo bodies. Other brain regions showed minor or inconsistent changes. In the second stage of the analysis, quantitative studies failed to reveal significant differences in the numbers of Marinesco bodies in CD versus controls, but confirmed a significantly lower Purkinje cell density in CD. Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD. The findings suggest that subtle neuropathological changes such as lower Purkinje cell density may be found in primary CD when relevant brain regions are investigated with appropriate methods. PMID:23195594

Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

PubMed

Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

2017-07-04

This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

Gender Differences of Brain Glucose Metabolic Networks Revealed by FDG-PET: Evidence from a Large Cohort of 400 Young Adults

PubMed Central

Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Background Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. Materials and Methods FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Results Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. Conclusion This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients. PMID:24358312

Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

PubMed

Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

Traumatic Brain Injury: An Educator's Manual. [Revised Edition.

ERIC Educational Resources Information Center

Fiegenbaum, Ed, Ed.; And Others

This manual for the Portland (Oregon) Public Schools presents basic information on providing educational services to children with traumatic brain injury (TBI). Individual sections cover the following topics: the brain, central nervous system and behavior; physical, psychological and emotional implication; traumatic brain injury in children versus…

Histopathologic and Molecular Characterization of Sarcocystis calchasi Encephalitis in White-winged Doves ( Zenaida asiatica ) and Eurasian Collared Doves ( Streptopelia decaocto ), East-central Texas, USA, 2010-13.

PubMed

Hodo, Carolyn L; Whitley, Derick B; Hamer, Sarah A; Corapi, Wayne V; Snowden, Karen; Heatley, J Jill; Hoffmann, Aline Rodrigues

2016-04-28

Sarcocystis calchasi is a recently described apicomplexan parasite that causes encephalitis in avian hosts. We diagnosed one White-winged Dove ( Zenaida asiatica ) and two Eurasian Collared Doves ( Streptopelia decaocto ) in Texas, US, with a history of neurologic signs with protozoal encephalitis. On histologic examination, all three doves had moderate to severe meningoencephalitis characterized by large numbers of plasma cells, lymphocytes, and macrophages with gliosis and astrocytosis. Brain sections from two doves also contained numerous Mott cells. Protozoal schizonts with rosettes or clusters of individual merozoites consistent with Sarcocystis spp. were seen within areas of inflammation. Sarcocysts were also identified in the skeletal muscle of one dove. The PCR and sequencing of brain and skeletal muscle from two doves revealed 99% identity with S. calchasi. The presence of S. calchasi in fatal cases of encephalitis in doves in Texas suggests that the geographic and host ranges of S. calchasi are broader than previously reported.

Connectivity patterns during music listening: Evidence for action-based processing in musicians.

PubMed

Alluri, Vinoo; Toiviainen, Petri; Burunat, Iballa; Kliuchko, Marina; Vuust, Peter; Brattico, Elvira

2017-06-01

Musical expertise is visible both in the morphology and functionality of the brain. Recent research indicates that functional integration between multi-sensory, somato-motor, default-mode (DMN), and salience (SN) networks of the brain differentiates musicians from non-musicians during resting state. Here, we aimed at determining whether brain networks differentially exchange information in musicians as opposed to non-musicians during naturalistic music listening. Whole-brain graph-theory analyses were performed on participants' fMRI responses. Group-level differences revealed that musicians' primary hubs comprised cerebral and cerebellar sensorimotor regions whereas non-musicians' dominant hubs encompassed DMN-related regions. Community structure analyses of the key hubs revealed greater integration of motor and somatosensory homunculi representing the upper limbs and torso in musicians. Furthermore, musicians who started training at an earlier age exhibited greater centrality in the auditory cortex, and areas related to top-down processes, attention, emotion, somatosensory processing, and non-verbal processing of speech. We here reveal how brain networks organize themselves in a naturalistic music listening situation wherein musicians automatically engage neural networks that are action-based while non-musicians use those that are perception-based to process an incoming auditory stream. Hum Brain Mapp 38:2955-2970, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Simultaneous measurement of cerebral blood flow and mRNA signals: pixel-based inter-modality correlational analysis.

PubMed

Zhao, W; Busto, R; Truettner, J; Ginsberg, M D

2001-07-30

The analysis of pixel-based relationships between local cerebral blood flow (LCBF) and mRNA expression can reveal important insights into brain function. Traditionally, LCBF and in situ hybridization studies for genes of interest have been analyzed in separate series. To overcome this limitation and to increase the power of statistical analysis, this study focused on developing a double-label method to measure local cerebral blood flow (LCBF) and gene expressions simultaneously by means of a dual-autoradiography procedure. A 14C-iodoantipyrine autoradiographic LCBF study was first performed. Serial brain sections (12 in this study) were obtained at multiple coronal levels and were processed in the conventional manner to yield quantitative LCBF images. Two replicate sections at each bregma level were then used for in situ hybridization. To eliminate the 14C-iodoantipyrine from these sections, a chloroform-washout procedure was first performed. The sections were then processed for in situ hybridization autoradiography for the probes of interest. This method was tested in Wistar rats subjected to 12 min of global forebrain ischemia by two-vessel occlusion plus hypotension, followed by 2 or 6 h of reperfusion (n=4-6 per group). LCBF and in situ hybridization images for heat shock protein 70 (HSP70) were generated for each rat, aligned by disparity analysis, and analyzed on a pixel-by-pixel basis. This method yielded detailed inter-modality correlation between LCBF and HSP70 mRNA expressions. The advantages of this method include reducing the number of experimental animals by one-half; and providing accurate pixel-based correlations between different modalities in the same animals, thus enabling paired statistical analyses. This method can be extended to permit correlation of LCBF with the expression of multiple genes of interest.

Chronic traumatic encephalopathy (CTE) in a National Football League Player: Case report and emerging medicolegal practice questions.

PubMed

Omalu, Bennet I; Hamilton, Ronald L; Kamboh, M Ilyas; DeKosky, Steven T; Bailes, Julian

2010-01-01

We present a case of chronic traumatic encephalopathy (CTE) in a retired National Football League (NFL) Player with autopsy findings, apolipoprotein E genotype, and brain tissue evidence of chronic brain damage. This 44-year-old retired NFL player manifested a premortem history of cognitive and neuropsychiatric impairment, which included in part, chronic depression, suicide attempts, insomnia, paranoia, and impaired memory before he finally committed suicide. A full autopsy was performed with Polymerase Chain Reaction-based analyses of his blood to determine the apolipoprotein genotype. Histochemical and immunohistochemical analyses were performed on topographical gross sections of the brain. Autopsy confirmed a fatal gunshot wound of the head. The apolipoprotein E genotype was E3/E3 and the brain tissue revealed diffuse cerebral taupathy (Neurofibrillary Tangles and Neuritic Threads). This will be the third case of CTE in a national football player, which has been reported in the medical literature. Omalu et al., reported the first two cases in 2005 and 2006. This case series manifested similar premortem history of neuropsychiatric impairment with autopsy evidence of cerebral taupathy without any neuritic amyloidopathy. For a definitive diagnosis of CTE to be made, and for medicolegal purposes, a full autopsy must be performed with histochemical and immunohistochemical analyses of the brain to identify the presence of Neurofibrillary Tangles (NFTs) and Neuritic Threads (NTs). Further longitudinal prospective studies are required to confirm the common denominators and epidemiology of CTE in professional American football players, which have been identified by this case series.

Mapping subcortical brain maturation during adolescence: evidence of hemisphere- and sex-specific longitudinal changes.

PubMed

Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B

2013-09-01

Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes. Automated segmentation techniques optimized for longitudinal measurement were used to delineate volumes of the caudate, putamen, nucleus accumbens, pallidum, hippocampus, thalamus and the whole brain. Amygdala volumes were described using manual tracing methods. The results revealed heterogeneous maturation across the regions of interest (ROIs), and change was differentially moderated by sex and hemisphere. The caudate, thalamus and putamen declined in volume, more for females relative to males, and decreases in the putamen and thalamus were greater in the left hemisphere. The pallidum increased in size, but more so in the left hemisphere. While the left nucleus accumbens increased in size, the right accumbens decreased in size over the follow-up period. Increases in hippocampal volume were greater in the right hemisphere. While amygdala volume did not change over time, the left hemisphere was consistently larger than the right. These results suggest that subcortical brain development from early to middle adolescence is characterized by striking hemispheric specialization and sexual dimorphisms, and provide a framework for interpreting normal and abnormal changes in cognition, affect and behavior. Moreover, the differences in findings compared to previous cross-sectional research emphasize the importance of within-subject assessment of brain development during adolescence. © 2013 John Wiley & Sons Ltd.

Multi-modal spectroscopic imaging with synchrotron light to study mechanisms of brain disease

NASA Astrophysics Data System (ADS)

Summers, Kelly L.; Fimognari, Nicholas; Hollings, Ashley; Kiernan, Mitchell; Lam, Virginie; Tidy, Rebecca J.; Takechi, Ryu; George, Graham N.; Pickering, Ingrid J.; Mamo, John C.; Harris, Hugh H.; Hackett, Mark J.

2017-04-01

The international health care costs associated with Alzheimer's disease (AD) and dementia have been predicted to reach $2 trillion USD by 2030. As such, there is urgent need to develop new treatments and diagnostic methods to stem an international health crisis. A major limitation to therapy and diagnostic development is the lack of complete understanding about the disease mechanisms. Spectroscopic methods at synchrotron light sources, such as FTIR, XRF, and XAS, offer a "multi-modal imaging platform" to reveal a wealth of important biochemical information in situ within ex vivo tissue sections, to increase our understanding of disease mechanisms.

Diffusion Tensor Imaging Tractography Detecting Isolated Oculomotor Nerve Damage After Traumatic Brain Injury.

PubMed

Jacquesson, Timothée; Frindel, Carole; Cotton, Francois

2017-04-01

A 24-year-old woman was hit by a bus and suffered an isolated complete oculomotor nerve palsy. Computed tomography scan did not show a skull base fracture. T2*-weighted magnetic resonance imaging revealed petechial cerebral hemorrhages sparing the brainstem. T2 constructive interference in steady state suggested a partial sectioning of the left oculomotor nerve just before entering the superior orbital fissure. Diffusion tensor imaging fiber tractography confirmed a sharp arrest of the left oculomotor nerve. This recent imaging technique could be of interest to assess white fiber damage and help make a diagnosis or prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Degenerative encephalopathy in a coastal mountain kingsnake (Lampropeltis zonata multifasciata) due to adenoviral-like infection.

PubMed

Raymond, James T; Lamm, Marnie; Nordhausen, Robert; Latimer, Ken; Garner, Michael M

2003-04-01

In March 2000, an approximately 30-yr-old, male coastal mountain kingsnake (Lampropeltis zonata multifasciata) presented with disequilibrium and unresponsiveness to stimuli that ultimately lead to euthanasia. Histologically, there were foci of gliosis primarily within the caudal cerebrum, brainstem, and cervical spinal cord. Several glial cells and endothelial cells contained magenta, intranuclear inclusion bodies. Electron microscopy of the inclusions revealed paracrystalline arrays of 79-82 nm, viral-like particles. DNA in situ hybridization of sections of formalin-fixed brain using a mixture of two digoxigenin-end-labeled, adenovirus specific, oligonucleotide probes at low and high stringency was positive for adenovirus.

Music Education and the Brain: What Does It Take to Make a Change?

ERIC Educational Resources Information Center

Collins, Anita

2014-01-01

Neuroscientists have worked for over two decades to understand how the brain processes music, affects emotions, and changes brain development. Much of this research has been based on a model that compares the brain function of participants classified as musicians and nonmusicians. This body of knowledge reveals a large number of benefits from…

Cognitive Development in Children with Brain Damage.

ERIC Educational Resources Information Center

Bortner, Morton

Presented is a report on a cross-sectional and longitudinal study concerned with the course of intellectual development in 210 children (6-12 years old) educationally designated as brain damaged (learning disabled and/or behavior problems) and assigned to special school placement. The report is divided into four sections which focus on…

Consecutive light microscopy, scanning-transmission electron microscopy and transmission electron microscopy of traumatic human brain oedema and ischaemic brain damage.

PubMed

Castejon, O J; Castejon, H V; Diaz, M; Castellano, A

2001-10-01

Cortical biopsies of 11 patients with traumatic brain oedema were consecutively studied by light microscopy (LM) using thick plastic sections, scanning-transmission electron microscopy ((S)TEM) using semithin plastic sections and transmission electron microscopy (TEM) using ultrathin sections. Samples were glutaraldehyde-osmium fixed and embedded in Araldite or Epon. Thick sections were stained with toluidine-blue for light microscopy. Semithin sections were examined unstained and uncoated for (S)TEM. Ultrathin sections were stained with uranyl and lead. Perivascular haemorrhages and perivascular extravasation of proteinaceous oedema fluid were observed in both moderate and severe oedema. Ischaemic pyramidal and non-pyramidal nerve cells appeared shrunken, electron dense and with enlargement of intracytoplasmic membrane compartment. Notably swollen astrocytes were observed in all samples examined. Glycogen-rich and glycogen-depleted astrocytes were identified in anoxic-ischaemic regions. Dark and hydropic satellite, interfascicular and perivascular oligodendrocytes were also found. The status spongiosus of severely oedematous brain parenchyma observed by LM and (S)TEM was correlated with the enlarged extracellular space and disrupted neuropil observed by TEM. The (S)TEM is recommended as a suitable technique for studying pathological processes in the central nervous system and as an informative adjunct to LM and TEM.

Spontaneous thrombosis of the main draining vein revealing an unruptured brain arteriovenous malformation

PubMed Central

Cao, Catherine; Sourour, Nader; Reina, Vincent; Nouet, Aurélien; Di Maria, Federico; Chiras, Jacques; Cornu, Philippe

2015-01-01

Haemorrhage is the most frequent revealing condition of brain arteriovenous malformations (bAVMs). We report a rare case of unruptured parietal bAVM revealed by spontaneous thrombosis of the main draining vein, responsible for a focal neurological deficit. The bAVM was embolized in emergency conditions; complete regression of the neurological symptoms was observed within five days after the embolization. Potential mechanisms of such spontaneous thrombosis of the bAVM’s main drainage pathway as well as an exhaustive review of the literature concerning this rare revealing condition are presented and discussed. PMID:25964440

G-protein-coupled estrogen receptor 1 is involved in brain development during zebrafish (Danio rerio) embryogenesis

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

Shi, Yanan; Liu, Xiaochun; Zhu, Pei

Highlights: •The Gper expression was detected in the developing brain of zebrafish. •Gper morpholino knockdown induced apoptosis of brain cells. •Gper morpholino knockdown reduced expression in neuron markers. •Zebrafish Gper may be involved in neuronal development. -- Abstract: G-protein-coupled estrogen receptor 1 (Gper, formerly known as GPR30) is found to be a trophic and protective factor in mediating action of estrogen in adult brain, while its role in developing brain remains to be elucidated. Here we present the expression pattern of Gper and its functions during embryogenesis in zebrafish. Both the mRNA and protein of Gper were detected throughout embryogenesis.more » Whole mount in situ hybridization (WISH) revealed a wide distribution of gper mRNAs in various regions of the developing brain. Gper knockdown by specific morpholinos resulted in growth retardation in embryos and morphological defects in the developing brain. In addition, induced apoptosis, decreased proliferation of the brain cells and maldevelopment of sensory and motor neurons were also found in the morphants. Our results provide novel insights into Gper functions in the developing brain, revealing that Gper can maintain the survival of the brain cells, and formation and/or differentiation of the sensory and motor neurons.« less

Anatomic brain disease in hemodialysis patients: a cross-sectional study

USDA-ARS?s Scientific Manuscript database

Although dialysis patients are at high risk of stroke and have a high burden of cognitive impairment, there are few reports of anatomic brain findings in the hemodialysis population. Using magnetic resonance imaging of the brain, we compared the prevalence of brain abnormalities in hemodialysis pati...

Perivascular Accumulation of β-Sheet-Rich Proteins in Offspring Brain following Maternal Exposure to Carbon Black Nanoparticles.

PubMed

Onoda, Atsuto; Kawasaki, Takayasu; Tsukiyama, Koichi; Takeda, Ken; Umezawa, Masakazu

2017-01-01

Environmental stimulation during brain development is an important risk factor for the development of neurodegenerative disease. Clinical evidence indicates that prenatal exposure to particulate air pollutants leads to diffuse damage to the neurovascular unit in the developing brain and accelerates neurodegeneration. Maternal exposure to carbon black nanoparticles (CB-NPs), used as a model for particulate air pollution, induces long-lasting diffuse perivascular abnormalities. We aimed to comprehensively characterize the perivascular abnormalities related to maternal NPs exposure using Fourier transform infrared microspectroscopy ( in situ FT-IR) and classical staining analysis. Pregnant ICR mice were intranasally treated with a CB-NPs suspension (95 μg/kg at a time) on gestational days 5 and 9. Brains were collected 6 weeks after birth and sliced to prepare 10-μm-thick serial sections. Reflective spectra of in situ FT-IR were acquired using lattice measurements ( x -axis: 7, y -axis: 7, 30-μm apertures) around a centered blood vessel. We also performed mapping analysis of protein secondary structures. Serial sections were stained with using periodic acid-Schiff or immunofluorescence to examine the phenotypes of the perivascular areas. Peaks of amide I bands in spectra from perivascular areas were shifted by maternal NPs exposure. However, there were two types of peak-shift in one mouse in the exposure group. Some vessels had a large peak-shift and others had a small peak-shift. In situ FT-IR combined with traditional staining revealed that the large peak-shift was induced around blood vessel adjacent to astrocytes with glial fibrillary acidic protein and aquaporin-4 over-expression and perivascular macrophages (PVMs) with enlarged lysosome granules. Furthermore, protein secondary structural analysis indicated that maternal NPs exposure led to increases in β-sheet content and decreases in α-helix content in areas that are mostly close to the centered blood vessel displaying histopathological changes. These results suggest that β-sheet-rich waste proteins, which are denatured by maternal NPs exposure, likely accumulate in the perivascular space as they are processed by the clearance systems in the brain. This may in turn lead the denaturation of PVMs and astrocyte activation. The risk of neurodegeneration may be enhanced by exposure to particulate air pollutants during brain development following the perivascular accumulation of β-sheet-rich waste proteins.

Reliability of a novel, semi-quantitative scale for classification of structural brain magnetic resonance imaging in children with cerebral palsy.

PubMed

Fiori, Simona; Cioni, Giovanni; Klingels, Katrjin; Ortibus, Els; Van Gestel, Leen; Rose, Stephen; Boyd, Roslyn N; Feys, Hilde; Guzzetta, Andrea

2014-09-01

To describe the development of a novel rating scale for classification of brain structural magnetic resonance imaging (MRI) in children with cerebral palsy (CP) and to assess its interrater and intrarater reliability. The scale consists of three sections. Section 1 contains descriptive information about the patient and MRI. Section 2 contains the graphical template of brain hemispheres onto which the lesion is transposed. Section 3 contains the scoring system for the quantitative analysis of the lesion characteristics, grouped into different global scores and subscores that assess separately side, regions, and depth. A larger interrater and intrarater reliability study was performed in 34 children with CP (22 males, 12 females; mean age at scan of 9 y 5 mo [SD 3 y 3 mo], range 4 y-16 y 11 mo; Gross Motor Function Classification System level I, [n=22], II [n=10], and level III [n=2]). Very high interrater and intrarater reliability of the total score was found with indices above 0.87. Reliability coefficients of the lobar and hemispheric subscores ranged between 0.53 and 0.95. Global scores for hemispheres, basal ganglia, brain stem, and corpus callosum showed reliability coefficients above 0.65. This study presents the first visual, semi-quantitative scale for classification of brain structural MRI in children with CP. The high degree of reliability of the scale supports its potential application for investigating the relationship between brain structure and function and examining treatment response according to brain lesion severity in children with CP. © 2014 Mac Keith Press.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

PubMed Central

2012-01-01

Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD. PMID:22889284

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

PubMed

Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Studying brain-regulation of immunity with optogenetics and chemogenetics; A new experimental platform.

PubMed

Ben-Shaanan, Tamar; Schiller, Maya; Rolls, Asya

2017-10-01

The interactions between the brain and the immune system are bidirectional. Nevertheless, we have far greater understanding of how the immune system affects the brain than how the brain affects immunity. New technological developments such as optogenetics and chemogenetics (using DREADDs; Designer Receptors Exclusively Activated by Designer Drugs) can bridge this gap in our understanding, as they enable an unprecedented mechanistic and systemic analysis of the communication between the brain and the immune system. In this review, we discuss new experimental approaches for revealing neuronal circuits that can participate in regulation of immunity. In addition, we discuss methods, specifically optogenetics and chemogenetics, that enable targeted neuronal manipulation to reveal how different brain regions affect immunity. We describe how these techniques can be used as an experimental platform to address fundamental questions in psychoneuroimmunology and to understand how neuronal circuits associate with different psychological states can affect physiology. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative analysis of A-to-I editing in human and non-human primate brains reveals conserved patterns and context-dependent regulation of RNA editing.

PubMed

O'Neil, Richard T; Wang, Xiaojing; Morabito, Michael V; Emeson, Ronald B

2017-04-06

A-to-I RNA editing is an important process for generating molecular diversity in the brain through modification of transcripts encoding several proteins important for neuronal signaling. We investigated the relationships between the extent of editing at multiple substrate transcripts (5HT2C, MGLUR4, CADPS, GLUR2, GLUR4, and GABRA3) in brain tissue obtained from adult humans and rhesus macaques. Several patterns emerged from these studies revealing conservation of editing across primate species. Additionally, variability in the human population allows us to make novel inferences about the co-regulation of editing at different editing sites and even across different brain regions.

Multidentate (18)F-polypegylated styrylpyridines as imaging agents for Aβ plaques in cerebral amyloid angiopathy (CAA).

PubMed

Zha, Zhihao; Choi, Seok Rye; Ploessl, Karl; Lieberman, Brian P; Qu, Wenchao; Hefti, Franz; Mintun, Mark; Skovronsky, Daniel; Kung, Hank F

2011-12-08

β-Amyloid plaques (Aβ plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the Aβ plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of (18)F styrylpyridine derivatives with high molecular weights for selectively targeting Aβ plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a-c, display high binding affinities and specificity to Aβ plaques (K(i) = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [(18)F]8a shows labeling of β-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [(18)F]8a may be a useful PET imaging agent for selectively detecting Aβ plaques associated with cerebral vessels in the living human brain.

Fast assembling of neuron fragments in serial 3D sections.

PubMed

Chen, Hanbo; Iascone, Daniel Maxim; da Costa, Nuno Maçarico; Lein, Ed S; Liu, Tianming; Peng, Hanchuan

2017-09-01

Reconstructing neurons from 3D image-stacks of serial sections of thick brain tissue is very time-consuming and often becomes a bottleneck in high-throughput brain mapping projects. We developed NeuronStitcher, a software suite for stitching non-overlapping neuron fragments reconstructed in serial 3D image sections. With its efficient algorithm and user-friendly interface, NeuronStitcher has been used successfully to reconstruct very large and complex human and mouse neurons.

Connecting Brain Research to Classroom Learning: A Mixed-Method Study on How Teachers Apply Brain Research to Their Instruction

ERIC Educational Resources Information Center

McAteer, Todd C.

2010-01-01

Purpose. The purpose of this study was to examine how knowledgeable teachers are in utilizing brain-researched instructional strategies. The research focused on determining which brain-researched strategies are implemented, the accuracy with which they are employed, and the degree to which they are utilized. A literature review revealed the most…

[A Case of Subcortical Intracerebral Hemorrhage Caused by Underlying Oligodendroglioma Diagnosed through Long-Term Follow-Up].

PubMed

Kidoguchi, Masamune; Isozaki, Makoto; Hirose, Satoshi; Kitai, Ryuhei; Kikuta, Ken-Ichiro

2017-03-01

We report on a case of an oligodendroglioma that caused intracerebral hemorrhage, which was diagnosed by long-term follow-up. An 82-year-old man with underlying hypertrophic cardiomyopathy presented with weakness in the right upper extremity. Computed tomography and magnetic resonance imaging(MRI)showed intracerebral hemorrhage and focal brain edema. Since there was a discrepancy between hematoma and focal brain edema, we first diagnosed cardiogenic cerebral embolism. Six months later, MRI results showed an improvement of the brain edema; however, the lesion developed after a year. We suspected that this lesion included a brain tumor and performed an open surgical biopsy. Pathological examination revealed that the tumor was an oligodendroglioma(World Health Organization grade 2). Because brain tumors that are complicated with intratumoral bleeding are often highly malignant and the lesions gradually increase in size, it is relatively easy to make a precise diagnosis. However, in low-grade gliomas, the intracerebral hemorrhage and brain edema may occasionally improve in the short term. We show that a case with a discrepancy between hematoma and brain edema should be followed up for at least more than a year, even when initial MRI does not reveal a brain tumor .

Fluorophilia: Fluorophore-containing compounds adhere non-specifically to injured neurons

PubMed Central

Hawkins, Bridget E.; Frederickson, Christopher J.; DeWitt, Douglas S.; Prough, Donald S.

2012-01-01

Ionic (free) zinc (Zn2+) is implicated in apoptotic neuronal degeneration and death. In our attempt to examine the effects of Zn2+ in neurodegeneration following brain injury, we serendipitously discovered that injured neurons bind fluorescein moieties, either alone or as part of an indicator dye, in histologic sections. This phenomenon, that we have termed “fluorophilia”, is analogous to the ability of degenerating neuronal somata and axons to bind silver ions (argyrophilia — the basis of silver degeneration stains). To provide evidence that fluorophilia occurs in sections of brain tissue, we used a wide variety of indicators such as Fluoro-Jade (FJ), a slightly modified fluorescein sold as a marker for degenerating neurons; Newport Green, a fluorescein-containing Zn2+ probe; Rhod-5N, a rhodamine-containing Ca2+ probe; and plain fluorescein. All yielded remarkably similar staining of degenerating neurons in the traumatic brain-injured tissue with the absence of staining in our sham-injured brains. Staining of presumptive injured neurons by these agents was not modified when Zn2+ in the brain section was removed by prior chelation with EDTA or TPEN, whereas staining by a non-fluorescein containing Zn2+ probe, N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ), was suppressed by prior chelation. Thus, certain fluorophore-containing compounds nonspecifically stain degenerating neuronal tissue in histologic sections and may not reflect the presence of Zn2+. This may be of concern to researchers using indicator dyes to detect metals in brain tissue sections. Further experiments may be advised to clarify whether Zn2+-binding dyes bind more specifically in intact neurons in culture or organotypic slices. PMID:22137653

A Primer on Brain Imaging in Developmental Psychopathology: What Is It Good For?

ERIC Educational Resources Information Center

Pine, Daniel S.

2006-01-01

This primer introduces a Special Section on brain imaging, which includes a commentary and 10 data papers presenting applications of brain imaging to questions on developmental psychopathology. This primer serves two purposes. First, the article summarizes the strength and weaknesses of various brain-imaging techniques typically employed in…

Best Practices for Young Children's Music Education: Guidance from Brain Research

ERIC Educational Resources Information Center

Flohr, John W.

2010-01-01

This article reviews best practices for young children's music experiences in light of developments in brain research. The first section reviews research music and brain topics including neuromyths, effect of music on structural brain changes and general intelligence, plasticity, critical and optimal periods, and at-risk student populations. The…

Cloning the Antibody Response in Humans with Chronic Inflammatory Disease: Immunopanning of Subacute Sclerosing Panencephalitis (SSPE) Brain Sections with Antibody Phage Libraries Prepared from SSPE Brain Enriches for Antibody Recognizing Measles Virus Antigens In Situ

PubMed Central

Owens, Gregory P.; Williamson, R. Anthony; Burgoon, Mark P.; Ghausi, Omar; Burton, Dennis R.; Gilden, Donald H.

2000-01-01

In central nervous system (CNS) infectious and inflammatory diseases of known cause, oligoclonal bands represent antibody directed against the causative agent. To determine whether disease-relevant antibodies can be cloned from diseased brain, we prepared an antibody phage display library from the brain of a human with subacute sclerosing panencephalitis (SSPE), a chronic encephalitis caused by measles virus, and selected the library against SSPE brain sections. Antibodies that were retrieved reacted strongly with measles virus cell extracts by enzyme-linked immunosorbent assay and were specific for the measles virus nucleocapsid protein. These antibodies immunostained cells in different SSPE brains but not in control brain. Our data provide the first demonstration that diseased brain can be used to select in situ for antibodies directed against the causative agent of disease and point to the potential usefulness of this approach in identifying relevant antibodies in chronic CNS or systemic inflammatory diseases of unknown cause. PMID:10627565

Teaching Both Sides of the Brain: Book II: Reading.

ERIC Educational Resources Information Center

Dombrower, Jule; And Others

Part of a program to increase the academic growth of preschool and primary grade students through the utilization of brain hemisphere research, this volume contains lessons designed to improve basic reading skills. Material is divided into two sections. Section 1 contains 17 activities to develop letter and word recognition. In activities 1-12,…

Slice-to-Volume Nonrigid Registration of Histological Sections to MR Images of the Human Brain

PubMed Central

Osechinskiy, Sergey; Kruggel, Frithjof

2011-01-01

Registration of histological images to three-dimensional imaging modalities is an important step in quantitative analysis of brain structure, in architectonic mapping of the brain, and in investigation of the pathology of a brain disease. Reconstruction of histology volume from serial sections is a well-established procedure, but it does not address registration of individual slices from sparse sections, which is the aim of the slice-to-volume approach. This study presents a flexible framework for intensity-based slice-to-volume nonrigid registration algorithms with a geometric transformation deformation field parametrized by various classes of spline functions: thin-plate splines (TPS), Gaussian elastic body splines (GEBS), or cubic B-splines. Algorithms are applied to cross-modality registration of histological and magnetic resonance images of the human brain. Registration performance is evaluated across a range of optimization algorithms and intensity-based cost functions. For a particular case of histological data, best results are obtained with a TPS three-dimensional (3D) warp, a new unconstrained optimization algorithm (NEWUOA), and a correlation-coefficient-based cost function. PMID:22567290

An atlas of the prenatal mouse brain: gestational day 14.

PubMed

Schambra, U B; Silver, J; Lauder, J M

1991-11-01

A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer.

Experimental methods for testing the effects of neurotrophic peptide, ADNF-9, against alcohol-induced apoptosis during pregnancy in c57bl/6 mice.

PubMed

Sari, Youssef

2013-04-24

Experimental designs for investigating the effects of prenatal alcohol exposure during early embryonic stages in fetal brain growth are challenging. This is mostly due to the difficulty of microdissection of fetal brains and their sectioning for determination of apoptotic cells caused by prenatal exposure to alcohol. The experiments described here provide visualized techniques from mice breeding to the identification of cell death in fetal brain tissue. This study used C57BL/6 mice as the animal model for studying fetal alcohol exposure and the role of trophic peptide against alcohol-induced apoptosis. The breeding consists of a 2-hr matting window to determine the exact stage of embryonic age. An established fetal alcohol exposure model has been used in this study to determine the effects of prenatal alcohol exposure in fetal brains. This involves free access to alcohol or pair-fed liquid diets as the sole source of nutrients for the pregnant mice. The techniques involving dissection of fetuses and microdissection of fetal brains are described carefully, since the latter can be challenging. Microdissection requires a stereomicroscope and ultra-fine forceps. Step-by-step procedures for dissecting the fetal brains are provided visually. The fetal brains are dissected from the base of the primordium olfactory bulb to the base of the metencephalon. For investigating apoptosis, fetal brains are first embedded in gelatin using a peel-away mold to facilitate their sectioning with a vibratome apparatus. Fetal brains embedded and fixed in paraformaldehyde are easily sectioned, and the free floating sections can be mounted in superfrost plus slides for determination of apoptosis or cell death. TUNEL (TdT-mediated dUTP Nick End Labeling; TdT: terminal deoxynucleotidyl transferase) assay has been used to identify cell death or apoptotic cells. It is noteworthy that apoptosis and cell-mediated cytotoxicity are characterized by DNA fragmentation. Thus, the visualized TUNEL-positive cells are indicative of cell death or apoptotic cells. The experimental designs here provide information about the use of an established liquid diet for studying the effects of alcohol and the role of neurotrophic peptides during pregnancy in fetal brains. This involves breeding and feeding pregnant mice, microdissecting fetal brains, and determining apoptosis. Together, these visual and textual techniques might be a source for investigating prenatal exposure of harmful agents in fetal brains.

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology.

PubMed

Macdonald, Ian R; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2016-02-01

Acetylcholinesterase and butyrylcholinesterase accumulate with brain β-amyloid (Aβ) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Aβ plaques within the brain, cholinesterase-associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Aβ plaques has the potential to distinguish AD from cognitively normal older adults, with or without Aβ accumulation, during life. Current Aβ imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I-PIP), is described. Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Aβ imaging agent, 2-(4'-dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Aβ and cholinesterase activity to visualize Aβ plaque load for comparison with radioligand uptake. Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Aβ plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Aβ plaques from both AD and cognitively normal individuals. Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I-PIP, can detect cholinesterases associated with Aβ plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Aβ plaques. Imaging cholinesterase activity associated with Aβ plaques in the living brain may contribute to the definitive diagnosis of AD during life. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults

PubMed Central

Flodin, Pär; Jonasson, Lars S.; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C. J.

2017-01-01

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas. PMID:28848424

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults.

PubMed

Flodin, Pär; Jonasson, Lars S; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C J

2017-01-01

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO 2 -peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO 2 -peak was negativly related to BOLD-signal fluctuations (BOLD STD ) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO 2 -related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO 2 -peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

Oxytocin enhances inter-brain synchrony during social coordination in male adults

PubMed Central

Mu, Yan; Guo, Chunyan

2016-01-01

Recent brain imaging research has revealed oxytocin (OT) effects on an individual's brain activity during social interaction but tells little about whether and how OT modulates the coherence of inter-brain activity related to two individuals' coordination behavior. We developed a new real-time coordination game that required two individuals of a dyad to synchronize with a partner (coordination task) or with a computer (control task) by counting in mind rhythmically. Electroencephalography (EEG) was recorded simultaneously from a dyad to examine OT effects on inter-brain synchrony of neural activity during interpersonal coordination. Experiment 1 found that dyads showed smaller interpersonal time lags of counting and greater inter-brain synchrony of alpha-band neural oscillations during the coordination (vs control) task and these effects were reliably observed in female but not male dyads. Moreover, the increased alpha-band inter-brain synchrony predicted better interpersonal behavioral synchrony across all participants. Experiment 2, using a double blind, placebo-controlled between-subjects design, revealed that intranasal OT vs placebo administration in male dyads improved interpersonal behavioral synchrony in both the coordination and control tasks but specifically enhanced alpha-band inter-brain neural oscillations during the coordination task. Our findings provide first evidence that OT enhances inter-brain synchrony in male adults to facilitate social coordination. PMID:27510498

Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

PubMed

Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

2018-03-12

Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels.

PubMed

Hupe, Mike; Li, Minerva Xueting; Kneitz, Susanne; Davydova, Daria; Yokota, Chika; Kele-Olovsson, Julianna; Hot, Belma; Stenman, Jan M; Gessler, Manfred

2017-07-11

The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier, we also compared the brain endothelial translatome of wild-type mice with that of mice lacking the transcriptional cofactor β-catenin ( Ctnnb1 ). Our analysis revealed extensive molecular changes during the embryonic development of the brain endothelium. We identified genes encoding brain endothelium-specific transcription factors ( Foxf2 , Foxl2 , Foxq1 , Lef1 , Ppard , Zfp551 , and Zic3 ) that are associated with maturation of the blood-brain barrier and act downstream of the Wnt-β-catenin signaling pathway. Profiling of individual brain endothelial cells revealed substantial heterogeneity in the population. Nevertheless, the high abundance of Foxf2 , Foxq1 , Ppard , or Zic3 transcripts correlated with the increased expression of genes encoding markers of brain endothelial cell differentiation. Expression of Foxf2 and Zic3 in human umbilical vein endothelial cells induced the production of blood-brain barrier differentiation markers. This comprehensive data set may help to improve the engineering of in vitro blood-brain barrier models. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Enhanced Antigen Retrieval of Amyloid β Immunohistochemistry

PubMed Central

Kai, Hideaki; Ogino, Koichi; Hatsuta, Hiroyuki; Murayama, Shigeo; Kitamoto, Tetsuyuki

2012-01-01

Senile plaques, extracellular deposits of amyloid β peptide (Aβ), are one of the pathological hallmarks of Alzheimer disease (AD). As the standard immunohistochemical detection method for Aβ deposits, anti-Aβ immunohistochemistry combined with antigen retrieval (AR) by formic acid (FA) has been generally used. Here, we present a more efficient AR for Aβ antigen. On brain sections of AD and its mouse model, a double combination of either autoclave heating in EDTA buffer or digestion with proteinase K plus FA treatment reinforced Aβ immunoreactivity. A further triple combination of digestion with proteinase K (P), autoclave heating in EDTA buffer (A), and FA treatment (F), when employed in this order, gave a more enhanced immunoreactivity. Our PAF method prominently visualized various forms of Aβ deposits in AD that have not been clearly detected previously and revealed numerous minute-sized plaques both in AD and the mouse model. Quantification of Aβ loads showed that the AR effect by the PAF method was 1.86-fold (in the aged human brain) and 4.64-fold (in the mouse brain) higher than that by the FA method. Thus, the PAF method could have the potential to be the most sensitive tool so far to study Aβ pathology in AD and its mouse model. PMID:22821668

Insomnia symptoms and behavioural health symptoms in veterans 1 year after traumatic brain injury.

PubMed

Farrell-Carnahan, Leah; Barnett, Scott; Lamberty, Gregory; Hammond, Flora M; Kretzmer, Tracy S; Franke, Laura M; Geiss, Meghan; Howe, Laura; Nakase-Richardson, Risa

2015-01-01

Insomnia and behavioural health symptoms 1 year after traumatic brain injury (TBI) were examined in a clinical sample representative of veterans who received inpatient treatment for TBI-related issues within the Veterans Health Administration. This was a cross-sectional sub-study (n = 112) of the Polytrauma Rehabilitation Centres' traumatic brain injury model system programme. Prevalence estimates of insomnia, depression, general anxiety, nightmares, headache and substance use, stratified by injury severity, were derived. Univariate logistic regression was used to examine unadjusted effects for each behavioural health problem and insomnia by injury severity. Participants were primarily male, < 30 years old and high school educated. Twenty-nine per cent met study criteria for insomnia; those with mild TBI were significantly more likely to meet criteria (43%) than those with moderate/severe TBI (22%), χ(2)(1, n = 112) = 5.088, p ≤ 0.05. Univariable logistic regression analyses revealed depressive symptoms and general anxiety were significantly associated with insomnia symptoms after TBI of any severity. Headache and binge drinking were significantly inversely related to insomnia symptoms after moderate/severe TBI, but not MTBI. Veterans with history of TBI, of any severity, and current insomnia symptoms may be at increased risk for depression and anxiety 1 year after TBI.

5-Aminolevulinic Acid Accumulation in a Cerebral Infarction Mimicking High-Grade Glioma.

PubMed

Behling, Felix; Hennersdorf, Florian; Bornemann, Antje; Tatagiba, Marcos; Skardelly, Marco

2016-08-01

5-Aminolevulinic acid (5-ALA) has become an integral part in the neurosurgical treatment of malignant glioma. Over time, several other tumor entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection. This case report is the first description of 5-ALA accumulation in postischemic cerebral tissue. This evidence questions the assumption that 5-ALA accumulation in glioma is exclusively attributed to tumor infiltration. Instead, 5-ALA accumulation can also occur beyond the tumor borders and may be partially ascribed to inflammatory changes in the surrounding brain tissue. A 64-year old woman presented with episodes of apraxia and a ring-enhancing lesion in postcontrast T1-weighted magnetic resonance sequences suggestive of high grade glioma. Strong fluorescence was observed during 5-ALA-guided resection. However, although the frozen section was inconclusive, the final histopathologic examination revealed a stage II cerebral infarction. 5-ALA accumulation in postischemic cerebral tissue should be considered for intended supramarginal resections near eloquent brain regions. Therefore, sufficient preoperative imaging should regularly include magnetic resonance imaging spectroscopy and perfusion sequences to ascertain the proper diagnosis. Moreover, further research is warranted to determine the role of 5-ALA accumulation in postischemic and inflammatory brain tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

Spontaneous thrombosis of the main draining vein revealing an unruptured brain arteriovenous malformation.

PubMed

Cao, Catherine; Sourour, Nader; Reina, Vincent; Nouet, Aurélien; Di Maria, Federico; Chiras, Jacques; Cornu, Philippe; Clarençon, Frédéric

2015-04-01

Haemorrhage is the most frequent revealing condition of brain arteriovenous malformations (bAVMs). We report a rare case of unruptured parietal bAVM revealed by spontaneous thrombosis of the main draining vein, responsible for a focal neurological deficit. The bAVM was embolized in emergency conditions; complete regression of the neurological symptoms was observed within five days after the embolization. Potential mechanisms of such spontaneous thrombosis of the bAVM's main drainage pathway as well as an exhaustive review of the literature concerning this rare revealing condition are presented and discussed. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Diffusion and related transport mechanisms in brain tissue

NASA Astrophysics Data System (ADS)

Nicholson, Charles

2001-07-01

Diffusion plays a crucial role in brain function. The spaces between cells can be likened to the water phase of a foam and many substances move within this complicated region. Diffusion in this interstitial space can be accurately modelled with appropriate modifications of classical equations and quantified from measurements based on novel micro-techniques. Besides delivering glucose and oxygen from the vascular system to brain cells, diffusion also moves informational substances between cells, a process known as volume transmission. Deviations from expected results reveal how local uptake, degradation or bulk flow may modify the transport of molecules. Diffusion is also essential to many therapies that deliver drugs to the brain. The diffusion-generated concentration distributions of well-chosen molecules also reveal the structure of brain tissue. This structure is represented by the volume fraction (void space) and the tortuosity (hindrance to diffusion imposed by local boundaries or local viscosity). Analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. Theoretical and experimental approaches borrow from classical diffusion theory and from porous media concepts. Earlier studies were based on radiotracers but the recent methods use a point-source paradigm coupled with micro-sensors or optical imaging of macromolecules labelled with fluorescent tags. These concepts and methods are likely to be applicable elsewhere to measure diffusion properties in very small volumes of highly structured but delicate material.

Chronic caffeine ingestion causes microglia activation, but not proliferation in the healthy brain

PubMed Central

Steger, Rob; Kamal, Arifa; Lutchman, Sara; Intrabartolo, Liliana; Sohail, Rabia; Brumberg, Joshua C.

2014-01-01

Caffeine is the most popular psychoactive drug in the world which contributes to behavioral and metabolic changes when ingested. Within the central nervous system (CNS), caffeine has a high affinity for A1 and A2a adenosine receptors. Serving as an antagonist, caffeine affects the ability for adenosine to bind to these receptors. Caffeine has been shown to alter neuronal functioning through increasing spontaneous firing. However, the effects of caffeine on non-neuronal cells in the CNS has been not been studied extensively. Microglia are one phenotype of non-neuronal glia within the CNS. Acting as phagocytes, they contribute to the immune defense system of the brain and express A1 and A2a adenosine receptors. Caffeine, therefore, may affect microglia. In order to test this hypothesis, CD-1 mice were randomly placed into one of three groups: control, low caffeine (0.3g/L water) and high caffeine (1.0g/L water) and were allowed to drink freely for 30 days. Following 30 days, brain sections were stained to reveal microglia. Morphological reconstructions and density measurements were examined in cortical and subcortical areas including the primary sensory cortex, primary motor cortex and striatum. Results indicate that microglial density throughout the brain is decreased in the caffeine groups as compared to the control. Caffeine also impacted microglia morphology shortening process length and decreasing branching. These results suggest that chronic caffeine ingestion has a systemic impact on microglia density and their activation. PMID:24881873

Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies.

PubMed

Sakowski, Stacey A; Geddes, Timothy J; Thomas, David M; Levi, Edi; Hatfield, James S; Kuhn, Donald M

2006-04-26

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of the neurotransmitter serotonin. Once thought to be a single-gene product, TPH is now known to exist in two isoforms-TPH1 is found in the pineal and gut, and TPH2 is selectively expressed in brain. Heretofore, probes used for localization of TPH protein or mRNA could not distinguish between the TPH isoforms because of extensive homology shared by them at the nucleotide and amino acid level. We have produced monospecific polyclonal antibodies against TPH1 and TPH2 using peptide antigens from nonoverlapping sequences in the respective proteins. These antibodies allow the differentiation of TPH1 and TPH2 upon immunoblotting, immunoprecipitation, and immunocytochemical staining of tissue sections from brain and gut. TPH1 and TPH2 antibodies do not cross-react with either tyrosine hydroxylase or phenylalanine hydroxylase. Analysis of mouse tissues confirms that TPH1 is the predominant form expressed in pineal gland and in P815 mastocytoma cells with a molecular weight of 51 kDa. TPH2 is the predominant enzyme form expressed in brain extracts from mesencephalic tegmentum, striatum, and hippocampus with a molecular weight of 56 kDa. Antibody specificity against TPH1 and TPH2 is retained across mouse, rat, rabbit, primate, and human tissues. Antibodies that distinguish between the isoforms of TPH will allow studies of the differential regulation of their expression in brain and periphery.

Hypertensive brain stem encephalopathy.

PubMed

Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

2015-01-01

A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.

Music for Their Minds

ERIC Educational Resources Information Center

Shore, Rebecca; Strasser, Janis

2006-01-01

Hearing causes brain cells (neurons) to connect and neural networks to form. Advanced brain-scan technology and neuroscience research reveal that when children participate in music, the brain "light[s] up like a Christmas tree" in many different areas (Parr, Radford, & Snyder 1998, cited in Isenberg & Jalongo 2001, 159). The growing neural…

Automated Transmission-Mode Scanning Electron Microscopy (tSEM) for Large Volume Analysis at Nanoscale Resolution

PubMed Central

Kuwajima, Masaaki; Mendenhall, John M.; Lindsey, Laurence F.; Harris, Kristen M.

2013-01-01

Transmission-mode scanning electron microscopy (tSEM) on a field emission SEM platform was developed for efficient and cost-effective imaging of circuit-scale volumes from brain at nanoscale resolution. Image area was maximized while optimizing the resolution and dynamic range necessary for discriminating key subcellular structures, such as small axonal, dendritic and glial processes, synapses, smooth endoplasmic reticulum, vesicles, microtubules, polyribosomes, and endosomes which are critical for neuronal function. Individual image fields from the tSEM system were up to 4,295 µm2 (65.54 µm per side) at 2 nm pixel size, contrasting with image fields from a modern transmission electron microscope (TEM) system, which were only 66.59 µm2 (8.160 µm per side) at the same pixel size. The tSEM produced outstanding images and had reduced distortion and drift relative to TEM. Automated stage and scan control in tSEM easily provided unattended serial section imaging and montaging. Lens and scan properties on both TEM and SEM platforms revealed no significant nonlinear distortions within a central field of ∼100 µm2 and produced near-perfect image registration across serial sections using the computational elastic alignment tool in Fiji/TrakEM2 software, and reliable geometric measurements from RECONSTRUCT™ or Fiji/TrakEM2 software. Axial resolution limits the analysis of small structures contained within a section (∼45 nm). Since this new tSEM is non-destructive, objects within a section can be explored at finer axial resolution in TEM tomography with current methods. Future development of tSEM tomography promises thinner axial resolution producing nearly isotropic voxels and should provide within-section analyses of structures without changing platforms. Brain was the test system given our interest in synaptic connectivity and plasticity; however, the new tSEM system is readily applicable to other biological systems. PMID:23555711

Human brains found in a fire-affected 4000-years old Bronze Age tumulus layer rich in soil alkalines and boron in Kutahya, Western Anatolia.

PubMed

Altinoz, M A; Ince, B; Sav, A; Dincer, A; Cengiz, S; Mercan, S; Yazici, Z; Bilgen, M N

2014-02-01

Undecomposed human bodies and organs always attracted interest in terms of understanding biological tissue stability and immortality. Amongst these, cases of natural mummification found in glaciers, bog sediments and deserts caused even more attention. In 2010, an archeological excavation of a Bronze Age layer in a tumulus near the Western Anatolia city Kütahya revealed fire affected regions with burnt human skeletons and charred wooden objects. Inside of the cracked skulls, undecomposed brains were discernible. To analyze the burial taphonomy of the rare phenomenon of brain preservation, we analyzed brains, bone, teeth and surrounding soils elements using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Adipocere formation or saponification of postmortem tissue fat requires high levels of alkalinity and especially potassium. Indeed, ICP-MS analysis of the brain, teeth and bone and also of the surrounding soil revealed high levels of potassium, magnesium, aluminum and boron, which are compatible with the famous role of Kütahya in tile production with its soil containing high level of alkalines and tile-glazing boron. Fatty acid chromatography revealed simultaneous saturation of fats and protection of fragile unsaturated fatty acids consistent with soil-presence of both pro-oxidant and anti-oxidant trace metals. Computerized tomography revealed protection of diencephalic, metencephalic and occipital tissue in one of the best-preserved specimens. Boron was previously found as an intentional preservative of Tutankhamen and Deir el Bahari mummies. Here, in natural soil with its insect-repellant, anti-bacterial and fire-resistance qualities it may be a factor to preserve heat-affected brains as almost bioporcellain specimens. Copyright © 2013 Elsevier GmbH. All rights reserved.

77 FR 50508 - Brain-Pad, Inc; Analysis of Proposed Consent Order To Aid Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... FEDERAL TRADE COMMISSION [File No. 122 3073] Brain-Pad, Inc; Analysis of Proposed Consent Order To... instructions in the Request for Comment part of the SUPPLEMENTARY INFORMATION section below. Write ``Brain-Pad... September 17, 2012. Write ``Brain-Pad, File No. 122 3073'' on your comment. Your comment--including your...

Which brain networks related to art perception are we talking about?. Comment on "Move me, astonish me…" delight my eyes and brain: The Vienna Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates; by Matthew Pelowski et al.

NASA Astrophysics Data System (ADS)

Ayala, Francisco J.; Cela-Conde, Camilo J.

2017-07-01

The proposal by the Vienna Integrated Model of Art Perception (Pelowski et al., [4]; VIMAP, hereafter) is a valuable and much needed attempt to summarize and understand the cognitive processes underlying art perception. Very important in their model is, as expected, to ascertain the psychological and brain processes correlated with the perception of beauty in art works. In this commentary we'll focus exclusively on the consideration of VIMAP's section 5, ;Model stages and corresponding areas of the brain.; We'll examine the evidence advanced by VIMAP in the section about brain networks related to the perception of art.

Dual Sarcocystis neurona and Toxoplasma gondii infection in a northern sea otter from Washington state, USA

USGS Publications Warehouse

Lindsay, D.S.; Thomas, N.J.; Rosypal, A.C.; Dubey, J.P.

2001-01-01

Dual Sarcocystis neurona and Toxoplasma gondii infection was observed in a Northern sea otter from Washington, USA. The animal was found stranded, convulsed, and died shortly thereafter. Encephalitis caused by both S. neurona and T. gondii was demonstrated in histological sections of brain. Immunohistochemical examination of sections with S. neurona specific antisera demonstrated developmental stages that divided by endopolygeny and produced numerous merozoites. PCR of brain tissue from the sea otter using primer pairs JNB33/JNB54 resulted in amplification of a 1100 bp product. This PCR product was cut in to 884 and 216 bp products by Dra I but was not cut by Hinf I indicating that it was S. neurona [J. Parasitol. 85 (1999) 221]. No PCR product was detected in the brain of a sea otter which had no lesions of encephalitis. Examination of brain sections using T. gondii specific antisera demonstrated tachyzoites and tissue cysts of T. gondii. The lesions induced by T. gondii suggested that the sea otter was suffering from reactivated toxoplasmosis. T. gondii was isolated in mice inoculated with brain tissue. A cat that was fed infected mouse brain tissue excreted T. gondii oocysts which were infective for mice. This is apparently the first report of dual S. neurona and T. gondii in a marine mammal.

EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands

PubMed Central

Dai, Zhongxiang; de Souza, Joshua; Lim, Julian; Ho, Paul M.; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2017-01-01

Numerous studies have revealed various working memory (WM)-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n-back tasks at two difficulty levels, i.e., 0-back (control task) and 2-back (WM task). After preprocessing, Electroencephalogram (EEG) signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session) of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks. PMID:28553215

EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands.

PubMed

Dai, Zhongxiang; de Souza, Joshua; Lim, Julian; Ho, Paul M; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2017-01-01

Numerous studies have revealed various working memory (WM)-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n -back tasks at two difficulty levels, i.e., 0-back (control task) and 2-back (WM task). After preprocessing, Electroencephalogram (EEG) signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session) of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks.

Following the crowd: Brain Substrates of Long-Term Memory Conformity

PubMed Central

Edelson, Micah; Sharot, Tali; Dolan, Raymond J; Dudai, Yadin

2012-01-01

Human memory is strikingly susceptible to social influences, yet we know little about the underlying mechanisms. We examined how socially induced memory errors are generated in the brain by studying the memory of individuals exposed to recollections of others. Participants exhibited a strong tendency to conform to erroneous recollections of the group, producing both long-lasting and temporary errors, even when their initial memory was strong and accurate. Functional brain imaging revealed that social influence modified the neuronal representation of memory. Specifically, a particular brain signature of enhanced amygdala activity and enhanced amygdala-hippocampus connectivity predicted long-lasting, but not temporary memory alterations. Our findings reveal how social manipulation can alter memory and extend the known functions of the amygdala to encompass socially-mediated memory distortions. PMID:21719681

Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

ERIC Educational Resources Information Center

Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

2012-01-01

Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

Cerebro, lenguaje y comunicacion (Brain, Language, and Communication).

ERIC Educational Resources Information Center

Strejilevich, Leonardo

1978-01-01

Discusses the relationship between the brain, language, and communication in the following sections: (1) combining words, (2) language as a system, (3) language as a function of the brain, (4) the science of communication, and (5) language as a social institution. (NCR)

TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics

PubMed Central

Loziuk, Philip; Meier, Florian; Johnson, Caroline

2016-01-01

Quantitative methods for detection of biological molecules are needed more than ever before in the emerging age of “omics” and “big data.” Here, we provide an integrated approach for systematic analysis of the “lipidome” in tissue. To test our approach in a biological context, we utilized brain tissue selectively deficient for the transcription factor Specificity Protein 2 (Sp2). Conditional deletion of Sp2 in the mouse cerebral cortex results in developmental deficiencies including disruption of lipid metabolism. Silver (Ag) cationization was implemented for infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) to enhance the ion abundances for olefinic lipids, as these have been linked to regulation by Sp2. Combining Ag-doped and conventional IR-MALDESI imaging, this approach was extended to IR-MALDESI imaging of embryonic mouse brains. Further, our imaging technique was combined with bottom-up shotgun proteomic LC-MS/MS analysis and western blot for comparing Sp2 conditional knockout (Sp2-cKO) and wild-type (WT) cortices of tissue sections. This provided an integrated omics dataset which revealed many specific changes to fundamental cellular processes and biosynthetic pathways. In particular, step-specific altered abundances of nucleotides, lipids, and associated proteins were observed in the cerebral cortices of Sp2-cKO embryos. PMID:26942738

In Situ Detection of Autoreactive CD4 T Cells in Brain and Heart Using Major Histocompatibility Complex Class II Dextramers

PubMed Central

Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Jia, Ting; Elowsky, Christian; Li, Qingsheng; Zhou, You; Reddy, Jay

2014-01-01

This report demonstrates the use of major histocompatibility complex (MHC) class II dextramers for detection of autoreactive CD4 T cells in situ in myelin proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) in SJL mice and cardiac myosin heavy chain-α (Myhc) 334-352-induced experimental autoimmune myocarditis (EAM) in A/J mice. Two sets of cocktails of dextramer reagents were used, where dextramers+ cells were analyzed by laser scanning confocal microscope (LSCM): EAE, IAs/PLP 139-151 dextramers (specific)/anti-CD4 and IAs/Theiler’s murine encephalomyelitis virus (TMEV) 70-86 dextramers (control)/anti-CD4; and EAM, IAk/Myhc 334-352 dextramers/anti-CD4 and IAk/bovine ribonuclease (RNase) 43-56 dextramers (control)/anti-CD4. LSCM analysis of brain sections obtained from EAE mice showed the presence of cells positive for CD4 and PLP 139-151 dextramers, but not TMEV 70-86 dextramers suggesting that the staining obtained with PLP 139-151 dextramers was specific. Likewise, heart sections prepared from EAM mice also revealed the presence of Myhc 334-352, but not RNase 43-56-dextramer+ cells as expected. Further, a comprehensive method has also been devised to quantitatively analyze the frequencies of antigen-specific CD4 T cells in the ‘Z’ serial images. PMID:25145797

Decreased Callosal Thickness in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Luders, Eileen; Narr, Katherine L.; Hamilton, Liberty S.; Phillips, Owen R.; Thompson, Paul M.; Valle, Jessica S.; Del'Homme, Melissa; Strickland, Tony; McCracken, James T.; Toga, Arthur W.; Levitt, Jennifer G.

2009-01-01

Background Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed structural abnormalities in the brains of affected individuals. One of the most replicated alterations is a significantly smaller corpus callosum (CC), for which conflicting reports exist with respect to the affected callosal segments. Methods We applied novel surface-based geometrical modeling methods to establish the presence, direction, and exact location of callosal alterations in ADHD at high spatial resolution. For this purpose, we calculated the thickness of the CC at 100 equidistant midsagittal points in an age-matched male sample of 19 individuals with ADHD and 19 typically developing control subjects. Results In close agreement with many prior observations, the CC was shown to be significantly thinner in ADHD subjects in anterior and, particularly, posterior callosal sections. Covarying for intelligence did not significantly alter the observed ADHD effects. However, group differences were no longer present in anterior sections when covarying for brain volume and after excluding ADHD subjects comorbid for oppositional defiant disorder. Conclusions Decreased callosal thickness may be associated with fewer fibers or a decrease in the myelination of fibers connecting the parietal and prefrontal cortices. This might affect interhemispheric communication channels that are necessary to sustain attention or motor control, thus contributing to symptoms of hyperactivity and impulsivity, or inattention, observed in ADHD. Future studies are necessary to determine whether callosal abnormalities reflect maturational delays or persist into adulthood. PMID:18842255

Phylostratigraphic Profiles in Zebrafish Uncover Chordate Origins of the Vertebrate Brain

PubMed Central

Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

2015-01-01

An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan–eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. PMID:25415965

Detrended fluctuation analysis of human brain electroencephalogram

NASA Astrophysics Data System (ADS)

Pan, C. P.; Zheng, B.; Wu, Y. Z.; Wang, Y.; Tang, X. W.

2004-08-01

With the detrended fluctuation analysis, we investigate dynamics of human brain electroencephalogram. Long-range temporal correlation and scaling behavior are observed, and certain characteristic of the Alzheimer's disease is revealed.

Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

NASA Technical Reports Server (NTRS)

Schmidt, M. A.; Goodwin, T. J.

2014-01-01

Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus

PubMed Central

Hagan, Cindy C.; Graham, Julia M.E.; Tait, Roger; Widmer, Barry; van Nieuwenhuizen, Adrienne O.; Ooi, Cinly; Whitaker, Kirstie J.; Simas, Tiago; Bullmore, Edward T.; Lennox, Belinda R.; Sahakian, Barbara J.; Goodyer, Ian M.; Suckling, John

2015-01-01

Objective There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Method Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Results Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. Conclusions The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain. PMID:25685707

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

PubMed

Hagan, Cindy C; Graham, Julia M E; Tait, Roger; Widmer, Barry; van Nieuwenhuizen, Adrienne O; Ooi, Cinly; Whitaker, Kirstie J; Simas, Tiago; Bullmore, Edward T; Lennox, Belinda R; Sahakian, Barbara J; Goodyer, Ian M; Suckling, John

2015-01-01

There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Imaging mass spectrometry detection of gangliosides species in the mouse brain following transient focal cerebral ischemia and long-term recovery.

PubMed

Whitehead, Shawn N; Chan, Kenneth H N; Gangaraju, Sandhya; Slinn, Jacqueline; Li, Jianjun; Hou, Sheng T

2011-01-01

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18:1, d20:1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury.

Nuclear microscopy in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Makjanic, Jagoda; Watt, Frank

1999-04-01

The elemental composition of the two types of brain lesions which characterise Alzheimer's disease (AD) has been the subject of intense scrutiny over the last decade, ever since it was proposed that inorganic trace elements, particularly aluminium, might be implicated in the pathogenesis of the disease. The major evidence for this involvement was the detection of aluminium in the characteristic lesions of the AD brain; neuritic plaques and neurofibrillary tangles (NFTs). Using the powerful combination of Particle-Induced X-ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS) and Scanning Transmission Ion Microscopy (STIM), it is possible to image and analyse structures in brain sections without recourse to chemical staining. Previous results on elemental composition of senile plaques indicated the absence of aluminium at the 15 parts per million level. We have more recently focused on the analysis of neurofibrillary tangles (NFTs), destructive structural defects within neurons. Imaging and analysis of neurons in brain tissue presented a greater challenge due to the small dimensional size compared with the plaques. We describe the methodology and the results of imaging and analysing neurons in brain tissue sections using Nuclear Microscopy. Our results show that aluminium is not present in either neurons or surrounding tissue in unstained sections at the 20 ppm level, but can be observed in stained sections. We also report elemental concentrations showing significant elevations of phosphorus, sulphur, chlorine, iron and zinc.

Digital tissue and what it may reveal about the brain.

PubMed

Morgan, Josh L; Lichtman, Jeff W

2017-10-30

Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

Brain-wide maps of Fos expression during fear learning and recall.

PubMed

Cho, Jin-Hyung; Rendall, Sam D; Gray, Jesse M

2017-04-01

Fos induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which Fos induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide maps of Fos mRNA expression during auditory fear conditioning and recall in the setting of the home cage. These maps reveal a brain-wide pattern of Fos induction that is remarkably similar among fear conditioning, shock-only, tone-only, and fear recall conditions, casting doubt on the idea that Fos reveals auditory-specific sensory representations. Indeed, novel auditory tones lead to as much gene induction in visual as in auditory cortex, while familiar (nonconditioned) tones do not appreciably induce Fos anywhere in the brain. Fos expression levels do not correlate with physical activity, suggesting that they are not determined by behavioral activity-driven alterations in sensory experience. In the thalamus, Fos is induced more prominently in limbic than in sensory relay nuclei, suggesting that Fos may be most sensitive to emotional state. Thus, our data suggest that Fos expression during simple associative learning labels ensembles activated generally by arousal rather than specifically by a particular sensory cue. © 2017 Cho et al.; Published by Cold Spring Harbor Laboratory Press.

Brain-wide maps of Fos expression during fear learning and recall

PubMed Central

Cho, Jin-Hyung; Rendall, Sam D.; Gray, Jesse M.

2017-01-01

Fos induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which Fos induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide maps of Fos mRNA expression during auditory fear conditioning and recall in the setting of the home cage. These maps reveal a brain-wide pattern of Fos induction that is remarkably similar among fear conditioning, shock-only, tone-only, and fear recall conditions, casting doubt on the idea that Fos reveals auditory-specific sensory representations. Indeed, novel auditory tones lead to as much gene induction in visual as in auditory cortex, while familiar (nonconditioned) tones do not appreciably induce Fos anywhere in the brain. Fos expression levels do not correlate with physical activity, suggesting that they are not determined by behavioral activity-driven alterations in sensory experience. In the thalamus, Fos is induced more prominently in limbic than in sensory relay nuclei, suggesting that Fos may be most sensitive to emotional state. Thus, our data suggest that Fos expression during simple associative learning labels ensembles activated generally by arousal rather than specifically by a particular sensory cue. PMID:28331016

Wired for Mathematics: A Conversation with Brian Butterworth.

ERIC Educational Resources Information Center

D'Arcangelo, Marcia

2001-01-01

Interview with neuropsychologist Brain Butterworth about what research has revealed about how the brain learns abstract concepts such as mathematics and the implications of these findings for teaching mathematics. (PKP)

Human Behavior, Learning, and the Developing Brain: Typical Development

ERIC Educational Resources Information Center

Coch, Donna, Ed.; Fischer, Kurt W., Ed.; Dawson, Geraldine, Ed.

2010-01-01

This volume brings together leading authorities from multiple disciplines to examine the relationship between brain development and behavior in typically developing children. Presented are innovative cross-sectional and longitudinal studies that shed light on brain-behavior connections in infancy and toddlerhood through adolescence. Chapters…

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

PubMed

Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

2017-10-13

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

PubMed

Ngô, Huân M; Zhou, Ying; Lorenzi, Hernan; Wang, Kai; Kim, Taek-Kyun; Zhou, Yong; El Bissati, Kamal; Mui, Ernest; Fraczek, Laura; Rajagopala, Seesandra V; Roberts, Craig W; Henriquez, Fiona L; Montpetit, Alexandre; Blackwell, Jenefer M; Jamieson, Sarra E; Wheeler, Kelsey; Begeman, Ian J; Naranjo-Galvis, Carlos; Alliey-Rodriguez, Ney; Davis, Roderick G; Soroceanu, Liliana; Cobbs, Charles; Steindler, Dennis A; Boyer, Kenneth; Noble, A Gwendolyn; Swisher, Charles N; Heydemann, Peter T; Rabiah, Peter; Withers, Shawn; Soteropoulos, Patricia; Hood, Leroy; McLeod, Rima

2017-09-13

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PubMed

Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

2017-05-01

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.

PubMed

Li, Yuxin; Tafti, Bashir A; Shaba, Wisam; Berenji, Gholam R

2011-07-01

A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study.

Do the Brain Networks of Scientists Account for Their Superiority in Hypothesis-Generating?

ERIC Educational Resources Information Center

Lee, Jun-Ki

2012-01-01

Where do scientists' superior abilities originate from when generating a creative idea? What different brain functions are activated between scientists and i) general academic high school students and ii) science high school students when generating a biological hypothesis? To reveal brain level explanations for these questions, this paper…

From Neurons to Brainpower: Cognitive Neuroscience and Brain-Based Learning

ERIC Educational Resources Information Center

Phillips, Janet M.

2005-01-01

We have learned more about the brain in the past five years than the previous 100. Neuroimaging, lesion studies, and animal studies have revealed the intricate inner workings of the brain and learning. Synaptogenesis, pruning, sensitive periods, and plasticity have all become accepted concepts of cognitive neuroscience that are now being applied…

Enriching the Brain: How to Maximize Every Learner's Potential

ERIC Educational Resources Information Center

Jensen, Eric

2006-01-01

Eric Jensen, a leading expert in the translation of brain research into education, argues that students' achievement capacity is greatly underappreciated. Drawing from a wide range of neuroscience research as well as related studies, the author reveals that the human brain is far more dynamic and malleable than earlier believed. He offers a…

Brain abscess mimicking brain metastasis in breast cancer.

PubMed

Khullar, Pooja; Datta, Niloy R; Wahi, Inderjeet Kaur; Kataria, Sabeena

2016-03-01

61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acetylaspartate) ratios of ∼1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient's previous history. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

PubMed

Li, Wan; Yang, Chunlan; Shi, Feng; Wang, Qun; Wu, Shuicai; Lu, Wangsheng; Li, Shaowu; Nie, Yingnan; Zhang, Xin

2018-04-16

Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.

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.

A cytoarchitecture-driven myelin model reveals area-specific signatures in human primary and secondary areas using ultra-high resolution in-vivo brain MRI.

PubMed

Dinse, J; Härtwich, N; Waehnert, M D; Tardif, C L; Schäfer, A; Geyer, S; Preim, B; Turner, R; Bazin, P-L

2015-07-01

This work presents a novel approach for modelling laminar myelin patterns in the human cortex in brain MR images on the basis of known cytoarchitecture. For the first time, it is possible to estimate intracortical contrast visible in quantitative ultra-high resolution MR images in specific primary and secondary cytoarchitectonic areas. The presented technique reveals different area-specific signatures which may help to study the spatial distribution of cortical T1 values and the distribution of cortical myelin in general. It may lead to a new discussion on the concordance of cyto- and myeloarchitectonic boundaries, given the absence of such concordance atlases. The modelled myelin patterns are quantitatively compared with data from human ultra-high resolution in-vivo 7T brain MR images (9 subjects). In the validation, the results are compared to one post-mortem brain sample and its ex-vivo MRI and histological data. Details of the analysis pipeline are provided. In the context of the increasing interest in advanced methods in brain segmentation and cortical architectural studies, the presented model helps to bridge the gap between the microanatomy revealed by classical histology and the macroanatomy visible in MRI. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Biomechanical Analysis of Normal Brain Development during the First Year of Life Using Finite Strain Theory.

PubMed

Kim, Jeong Chul; Wang, Li; Shen, Dinggang; Lin, Weili

2016-12-02

The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.

Semilobar holoprosencephaly in a 12-month-old baby boy born to a primigravida patient with type 1 diabetes mellitus: a case report.

PubMed

Pallangyo, Pedro; Lyimo, Frederick; Nicholaus, Paulina; Makungu, Hilda; Mtolera, Maria; Mawenya, Isaac

2016-12-20

Holoprosencephaly is a rare spectrum of cephalic disorders resulting from a failure or incomplete division of the embryonic forebrain into distinct cerebral hemispheres. It is the most common brain malformation with an incidence of 1:250 during embryogenesis; however, owing to the associated high rates of spontaneous abortion the incidence is 1:16,000 among live deliveries. Pathogenesis of holoprosencephaly is complex and heterogeneous involving genetic abnormalities, teratogenic exposures, and syndromic associations. Among the teratogenic exposures, maternal diabetes is a well-established risk factor associated with a 200-fold increased incidence of holoprosencephaly. We report a case of a delayed diagnosis of semilobar holoprosencephaly in a 12-month-old baby boy of African descent who presented to us with a history of global developmental delay, erratic sleep patterns, and poor weight gain. He was born to a type 1 diabetes mellitus mother at 39+ weeks by emergency cesarean section due to fetal distress and breech presentation. The baby weighed 2315 g and had Apgar scores of 6/10 and 8/10 at 1 and 5 minutes respectively. A physical examination done at 12 months of age revealed a small-for-age child with a developmental age of 2 months. He had normal facies but a neurological examination revealed hypotonia in all four limbs. The rest of systemic examination was unremarkable. Hematological and biochemical investigations revealed normal findings except for iron deficiency anemia. The child also underwent magnetic resonance imaging of his brain which revealed distinctive features of semilobar holoprosencephaly. He was treated for iron deficiency anemia with Hemovit syrup (ferric ammonium citrate, folic acid, pyridoxine hydrochloride, cyanocobalamin, and zinc sulfate) 10 ml thrice daily, ferrous sulfate 10 mg once daily, folic acid 1 mg once daily, and multivitamin syrup 5 ml once daily. Furthermore, nutritional and genetic counseling was offered to his parents. In conclusion, although rare, holoprosencephaly is the commonest structural anomaly of the brain with a complex and multifactorial etiopathogenesis. It is prudent to diagnose it prenatally, classify its severity, and forge its prognosis so that parents are counseled early enough to make informed decisions especially where termination of pregnancy may be implicated.

Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

PubMed

Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J; Kertesz, Vilmos; Gan, Jinping

2016-03-25

Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites were studied. Major organs (brain, lung, liver, kidney and muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. In addition, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

DOE PAGES

Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.; ...

2015-11-03

Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed themore » same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.« less

Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

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

Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.

Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed themore » same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.« less

Development of large-scale functional brain networks in children.

PubMed

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-07-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

Brain bioavailability of human intravenous immunoglobulin and its transport through the murine blood–brain barrier

PubMed Central

St-Amour, Isabelle; Paré, Isabelle; Alata, Wael; Coulombe, Katherine; Ringuette-Goulet, Cassandra; Drouin-Ouellet, Janelle; Vandal, Milène; Soulet, Denis; Bazin, Renée; Calon, Frédéric

2013-01-01

Intravenous immunoglobulin (IVIg) is currently evaluated in clinical trials for the treatment of various disorders of the central nervous system. To assess its capacity to reach central therapeutic targets, the brain bioavailability of IVIg must be determined. We thus quantified the passage of IVIg through the blood–brain barrier (BBB) of C57Bl/6 mice using complementary quantitative and qualitative methodologies. As determined by enzyme-linked immunosorbent assay, a small proportion of systemically injected IVIg was detected in the brain of mice (0.009±0.001% of injected dose in the cortex) whereas immunostaining revealed localization mainly within microvessels and less frequently in neurons. Pharmacokinetic analyses evidenced a low elimination rate constant (0.0053  per hour) in the cortex, consistent with accumulation within cerebral tissue. In situ cerebral perfusion experiments revealed that a fraction of IVIg crossed the BBB without causing leakage. A dose-dependent decrease of brain uptake was consistent with a saturable blood-to-brain transport mechanism. Finally, brain uptake of IVIg after a subchronic treatment was similar in the 3xTg-AD mouse model of Alzheimer disease compared with nontransgenic controls. In summary, our results provide evidence of BBB passage and bioavailability of IVIg into the brain in the absence of BBB leakage and in sufficient concentration to interact with the therapeutic targets. PMID:24045402

Oxytocin enhances inter-brain synchrony during social coordination in male adults.

PubMed

Mu, Yan; Guo, Chunyan; Han, Shihui

2016-12-01

Recent brain imaging research has revealed oxytocin (OT) effects on an individual's brain activity during social interaction but tells little about whether and how OT modulates the coherence of inter-brain activity related to two individuals' coordination behavior. We developed a new real-time coordination game that required two individuals of a dyad to synchronize with a partner (coordination task) or with a computer (control task) by counting in mind rhythmically. Electroencephalography (EEG) was recorded simultaneously from a dyad to examine OT effects on inter-brain synchrony of neural activity during interpersonal coordination. Experiment 1 found that dyads showed smaller interpersonal time lags of counting and greater inter-brain synchrony of alpha-band neural oscillations during the coordination (vs control) task and these effects were reliably observed in female but not male dyads. Moreover, the increased alpha-band inter-brain synchrony predicted better interpersonal behavioral synchrony across all participants. Experiment 2, using a double blind, placebo-controlled between-subjects design, revealed that intranasal OT vs placebo administration in male dyads improved interpersonal behavioral synchrony in both the coordination and control tasks but specifically enhanced alpha-band inter-brain neural oscillations during the coordination task. Our findings provide first evidence that OT enhances inter-brain synchrony in male adults to facilitate social coordination. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Development of Large-Scale Functional Brain Networks in Children

PubMed Central

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-01-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

Environment and brain plasticity: towards an endogenous pharmacotherapy.

PubMed

Sale, Alessandro; Berardi, Nicoletta; Maffei, Lamberto

2014-01-01

Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.

Researching the Practice, Practicing the Research, and Promoting Responsible Policy: Usable Knowledge in Mind, Brain, and Education

ERIC Educational Resources Information Center

Christodoulou, Joanna A.; Daley, Samantha G.; Katzir, Tami

2009-01-01

The theme of Usable Knowledge in Mind, Brain, and Education will be a special section that will appear regularly in the journal. The section will focus on the synergistic connections between biology, cognitive science, and human development on the one hand and educational thought, policy, and practice on the other. Efforts to create usable…

Visuospatial asymmetries and interocular transfer in the split-brain rat.

PubMed

Adelstein, A; Crowne, D P

1991-06-01

Interocular transfer (IOT), hemispheric superiority, and cerebral dominance were examined in split-brain female albino rats. Callosum-sectioned and intact animals were monocularly trained in the Morris water maze and tested in IOT and reversal phases. In the IOT phase, split-brain rats entered more nontarget quadrants and headed less accurately toward the platform than did controls. For both split-brain animals and controls, right-eye training resulted in shorter latencies and fewer nontarget entries than did left-eye training. Analyses of cerebral dominance showed shorter latencies and smaller heading errors over all 3 phases in rats that were trained with the nondominant eye. Right-eye dominant controls were less affected by platform reversal. Split-brain rats were inferior to controls in latency to find the platform and in target quadrant entries. This finding establishes a spatial cognitive deficit from callosum section.

Effect of vitro preservation on mechanical properties of brain tissue

NASA Astrophysics Data System (ADS)

Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

2017-05-01

To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels.

PubMed

Schedin-Weiss, Sophia; Inoue, Mitsuhiro; Hromadkova, Lenka; Teranishi, Yasuhiro; Yamamoto, Natsuko Goto; Wiehager, Birgitta; Bogdanovic, Nenad; Winblad, Bengt; Sandebring-Matton, Anna; Frykman, Susanne; Tjernberg, Lars O

2017-08-01

Increased levels of the pathogenic amyloid β-peptide (Aβ), released from its precursor by the transmembrane protease γ-secretase, are found in Alzheimer disease (AD) brains. Interestingly, monoamine oxidase B (MAO-B) activity is also increased in AD brain, but its role in AD pathogenesis is not known. Recent neuroimaging studies have shown that the increased MAO-B expression in AD brain starts several years before the onset of the disease. Here, we show a potential connection between MAO-B, γ-secretase and Aβ in neurons. MAO-B immunohistochemistry was performed on postmortem human brain. Affinity purification of γ-secretase followed by mass spectrometry was used for unbiased identification of γ-secretase-associated proteins. The association of MAO-B with γ-secretase was studied by coimmunoprecipitation from brain homogenate, and by in-situ proximity ligation assay (PLA) in neurons as well as mouse and human brain sections. The effect of MAO-B on Aβ production and Notch processing in cell cultures was analyzed by siRNA silencing or overexpression experiments followed by ELISA, western blot or FRET analysis. Methodology for measuring relative intraneuronal MAO-B and Aβ42 levels in single cells was developed by combining immunocytochemistry and confocal microscopy with quantitative image analysis. Immunohistochemistry revealed MAO-B staining in neurons in the frontal cortex, hippocampus CA1 and entorhinal cortex in postmortem human brain. Interestingly, the neuronal staining intensity was higher in AD brain than in control brain in these regions. Mass spectrometric data from affinity purified γ-secretase suggested that MAO-B is a γ-secretase-associated protein, which was confirmed by immunoprecipitation and PLA, and a neuronal location of the interaction was shown. Strikingly, intraneuronal Aβ42 levels correlated with MAO-B levels, and siRNA silencing of MAO-B resulted in significantly reduced levels of intraneuronal Aβ42. Furthermore, overexpression of MAO-B enhanced Aβ production. This study shows that MAO-B levels are increased not only in astrocytes but also in pyramidal neurons in AD brain. The study also suggests that MAO-B regulates Aβ production in neurons via γ-secretase and thereby provides a key to understanding the relationship between MAO-B and AD pathogenesis. Potentially, the γ-secretase/MAO-B association may be a target for reducing Aβ levels using protein-protein interaction breakers.

GDNF family receptor α-1 in the catfish: Possible implication to brain dopaminergic activity.

PubMed

Mamta, Sajwan-Khatri; Senthilkumaran, Balasubramanian

2018-05-31

Glial cell line-derived neurotrophic factor (GDNF)is a potent trophic factor that preferentially binds to GDNF family receptor α-1 (GFRα-1)by regulating dopaminergic (DA-ergic) neuronsin brain. Present study aimed to evaluate the significance of GFRα-1 expression during early brain development in catfish. Initially, the full-length cDNA of GFRα-1 was cloned from adult brain which showed high homology with other vertebrate counterparts. Quantitative PCR analysis of tissue distribution revealed ubiquitous expression of GFRα-1 in the tissues analyzed with high levels in female brain and ovary. Significant high expression was evident in brain at 75 and 100 days post hatch females than the respective age-match males. Expression of GFRα-1 was high in brain during the spawning phase when compared to other reproductive phases. Localization of GFRα-1 revealed its presence in preoptic area-hypothalamus which correlated well with the expression profile in discrete areas of brain in adult catfish. Transient silencing of GFRα-1through siRNA lowered expression levels of GFRα-1, which further down regulated the expression of certain brain-specific genes. Expression of GFRα-1 in brain declined significantly upon treatment with the 1-methyl-1,2,3,6-tetrahydropyridinecausing neurodegeneration which further correlated with catecholamines (CA), L-3,4-dihydroxyphenylalanine, DA and norepinephrine levels. Taken together, GFRα-1 plausibly entrains gonadotropin-releasing hormone and gonadotropin axiseither directly or indirectly, at least by partially targeting CA-ergic activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional network organization of the human brain

PubMed Central

Power, Jonathan D; Cohen, Alexander L; Nelson, Steven M; Wig, Gagan S; Barnes, Kelly Anne; Church, Jessica A; Vogel, Alecia C; Laumann, Timothy O; Miezin, Fran M; Schlaggar, Bradley L; Petersen, Steven E

2011-01-01

Summary Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a “processing” system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex. PMID:22099467

Structure and function of complex brain networks

PubMed Central

Sporns, Olaf

2013-01-01

An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed. PMID:24174898

A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus.

PubMed

Newman, John D; Kenkel, William M; Aronoff, Emily C; Bock, Nicholas A; Zametkin, Molly R; Silva, Afonso C

2009-12-11

The common marmoset, Callithrix jacchus, is of growing importance for research in neuroscience and related fields. In the present work, we describe a combined histological and magnetic resonance imaging (MRI) atlas constructed from the brains of two adult female marmosets. Histological sections were processed from Nissl staining and digitized to produce an atlas in a large format that facilitates visualization of structures with significant detail. Naming of identifiable brain structures was performed utilizing current terminology. The histological sections and a simplified schematic atlas are available online at http://udn.nichd.nih.gov/brainatlas_home.html.

47-year-old man with left leg numbness.

PubMed

Mahta, Ali; Kim, Ryan Y; Saad, Ali G; Kesari, Santosh

2013-03-01

A 47-year-old white male with a history of uveitis, hypercalcemia and nephrolithiasis presented with acute onset partial seizure. On exam he had decreased sensation to light touch on his left lower extremity. A Brain MRI revealed a right frontal mass, which was initially thought to be a metastatic lesion or a primary brain tumor. However, biopsy of the lesion revealed it to be a non-caseating granulomatous lesion consistent with neurosarcoidosis.

Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

PubMed Central

Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

2012-01-01

Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

Evidence of native α-synuclein conformers in the human brain.

PubMed

Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry

2014-03-14

α-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of α-synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.

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

Phylostratigraphic profiles in zebrafish uncover chordate origins of the vertebrate brain.

PubMed

Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

2015-02-01

An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan-eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Aging, Brain Size, and IQ.

ERIC Educational Resources Information Center

Bigler, Erin D.; And Others

1995-01-01

Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

Predicting age from cortical structure across the lifespan.

PubMed

Madan, Christopher R; Kensinger, Elizabeth A

2018-03-01

Despite interindividual differences in cortical structure, cross-sectional and longitudinal studies have demonstrated a large degree of population-level consistency in age-related differences in brain morphology. This study assessed how accurately an individual's age could be predicted by estimates of cortical morphology, comparing a variety of structural measures, including thickness, gyrification and fractal dimensionality. Structural measures were calculated across up to seven different parcellation approaches, ranging from one region to 1000 regions. The age prediction framework was trained using morphological measures obtained from T1-weighted MRI volumes collected from multiple sites, yielding a training dataset of 1056 healthy adults, aged 18-97. Age predictions were calculated using a machine-learning approach that incorporated nonlinear differences over the lifespan. In two independent, held-out test samples, age predictions had a median error of 6-7 years. Age predictions were best when using a combination of cortical metrics, both thickness and fractal dimensionality. Overall, the results reveal that age-related differences in brain structure are systematic enough to enable reliable age prediction based on metrics of cortical morphology. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The hyperforin derivative IDN5706 occludes spatial memory impairments and neuropathological changes in a double transgenic Alzheimer's mouse model.

PubMed

Cerpa, W; Hancke, J L; Morazzoni, P; Bombardelli, E; Riva, Antonella; Marin, P P; Inestrosa, Nibaldo C

2010-03-01

The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropathology, learning and memory in a double transgenic (APPswe, PS-1dE9) mouse model of AD. Results indicate that, IDN5706 alleviates memory decline induced by amyloid-beta (Abeta) deposits as indicated by the Morris water maze paradigm. Moreover, the analysis of Abeta deposits by immunodetection and thioflavin-S staining of brain sections, only reveals a decrease in the frequency of the larger-size Abeta deposits, suggesting that IDN5706 affected the turnover of amyloid plaques. Immunohistochemical analysis, using GFAP and n-Tyrosine indicated that the hyperforin derivative prevents the inflammatory astrocytic reaction and the oxidative damage triggered by high Abeta deposit levels. We conclude that the hyperforin derivative, IDN5706, has therapeutic potential for prevention and treatment of AD.

Optical mapping of brain activation in gambling disorders

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lin, Xiaohong

2018-02-01

In this study, fNIRS was utilized to identify the brain activation difference between pathological gamblers (PGs) and heathy controls (HCs). We inspected the hemodynamic changes in the prefrontal cortex using fNIRS recordings during the completion of executive function and decision making tasks. Our finding revealed that the PG and HC groups exhibited significant differences in brain activation.

Dual Language Use in Sign-Speech Bimodal Bilinguals: fNIRS Brain-Imaging Evidence

ERIC Educational Resources Information Center

Kovelman, Ioulia; Shalinsky, Mark H.; White, Katherine S.; Schmitt, Shawn N.; Berens, Melody S.; Paymer, Nora; Petitto, Laura-Ann

2009-01-01

The brain basis of bilinguals' ability to use two languages at the same time has been a hotly debated topic. On the one hand, behavioral research has suggested that bilingual dual language use involves complex and highly principled linguistic processes. On the other hand, brain-imaging research has revealed that bilingual language switching…

Brain Research, Learning and Emotions: Implications for Education Research, Policy and Practice

ERIC Educational Resources Information Center

Hinton, Christina; Miyamoto, Koji; Della-Chiesa, Bruno

2008-01-01

Recent advancements in neuroscience heighten its relevance to education. Newly developed imaging technologies enable scientists to peer into the working brain for the first time, providing powerful insights into how we learn. Research reveals that the brain is not a stable and isolated entity, but a dynamic system that is keenly responsive to…

Different Brain Wave Patterns and Cortical Control Abilities in Relation to Different Creative Potentials

ERIC Educational Resources Information Center

Li, Ying-Han; Tseng, Chao-Yuan; Tsai, Arthur Chih-Hsin; Huang, Andrew Chih-Wei; Lin, Wei-Lun

2016-01-01

Contemporary understanding of brain functions provides a way to probe into the mystery of creativity. However, the prior evidence regarding the relationship between creativity and brain wave patterns reveals inconsistent conclusions. One possible reason might be that the means of selecting creative individuals in the past has varied in each study.…

Structural, Functional, and Metabolic Brain Markers Differentiate Collision versus Contact and Non-Contact Athletes

PubMed Central

Churchill, Nathan W.; Hutchison, Michael G.; Di Battista, Alex P.; Graham, Simon J.; Schweizer, Tom A.

2017-01-01

There is growing concern about how participation in contact sports affects the brain. Retrospective evidence suggests that contact sports are associated with long-term negative health outcomes. However, much of the research to date has focused on former athletes with significant health problems. Less is known about the health of current athletes in contact and collision sports who have not reported significant medical issues. In this cross-sectional study, advanced magnetic resonance imaging (MRI) was used to evaluate multiple aspects of brain physiology in three groups of athletes participating in non-contact sports (N = 20), contact sports (N = 22), and collision sports (N = 23). Diffusion tensor imaging was used to assess white matter microstructure based on measures of fractional anisotropy (FA) and mean diffusivity (MD); resting-state functional MRI was used to evaluate global functional connectivity; single-voxel spectroscopy was used to compare ratios of neural metabolites, including N-acetyl aspartate (NAA), creatine (Cr), choline, and myo-inositol. Multivariate analysis revealed structural, functional, and metabolic measures that reliably differentiated between sport groups. The collision group had significantly elevated FA and reduced MD in white matter, compared to both contact and non-contact groups. In contrast, the collision group showed significant reductions in functional connectivity and the NAA/Cr metabolite ratio, relative to only the non-contact group, while the contact group overlapped with both non-contact and collision groups. For brain regions associated with contact sport participation, athletes with a history of concussion also showed greater alterations in FA and functional connectivity, indicating a potential cumulative effect of both contact exposure and concussion history on brain physiology. These findings indicate persistent differences in brain physiology for athletes participating in contact and collision sports, which should be considered in future studies of concussion and subconcussive impacts. PMID:28878729

Cross sectional imaging of post partum headache and seizures.

PubMed

Hiremath, Rudresh; Mundaganur, Praveen; Sonwalkar, Pradeep; N S, Vishal; G S, Narendra; P, Sanjay

2014-12-01

To evaluate spectrum of causes & their characteristic findings in peripartum head ache and seizures on computed tomography & magnetic resonance imaging. Forty patients with complaints of peripartum headache and seizures underwent cross sectional imaging with computed tomography and magnetic resonance imaging during period of June 2011 to May 2012. Age group of subjects in this study was 18 to 38 y. Out of 40 patients 15 had history of eclampsia and remaining 25 patients were normotensive. Subjects with complaints of headache and seizures after six weeks of delivery were excluded from the study. Intravenous contrast was administered in cases with diagnostic dilemma. All results were reported and informed to the referring physicians on priority bases. Nine patients with peripartum headache and seizures revealed no brain parenchymal or cerebral vascular abnormalities on imaging. Eleven patients with a history of eclampsia showed features of eclamptic encephalopathy. Out 40 patients, 17 patients revealed cortical venous thrombosis with 14 patients showing parenchymal changes. One patient each showed features of meningoencephalitis, ischemic watershed territory infarct & region of gliosis. All results were analysed & tabulated. Eclamptic encephalopathy and cortical venous thrombosis are the major causes for post partum headache and seizures. Rational use of CT & MRI in the early course of the disease helps in characterizing the lesion and providing the appropriate treatment.

Trisomy 13

MedlinePlus

... the head may reveal a problem with the structure of the brain. The problem is called holoprosencephaly. It is the joining together of the 2 sides of the brain. Chromosome studies show trisomy 13, trisomy 13 mosaicism, or partial trisomy.

Complex Networks - A Key to Understanding Brain Function

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

Sporns, Olaf

2008-01-23

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

Brain abscess mimicking lung cancer metastases; a case report.

PubMed

Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

2013-01-01

A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

Complex Networks - A Key to Understanding Brain Function

ScienceCinema

Sporns, Olaf

2017-12-22

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

IMPY: an improved thioflavin-T derivative for in vivo labeling of beta-amyloid plaques.

PubMed

Kung, Mei-Ping; Hou, Catherine; Zhuang, Zhi-Ping; Zhang, Bin; Skovronsky, Daniel; Trojanowski, John Q; Lee, Virginia M-Y; Kung, Hank F

2002-11-29

Development of small molecular probes for in vivo labeling and detection of beta-amyloid (Abeta) plaques in patients of Alzheimer's disease (AD) is of significant scientific interest, and it may also assist the development of drugs targeting Abeta plaques for treatment of AD. A novel probe, [123I/(125)I]IMPY, 6-iodo-2-(4'-dimethylamino-)phenyl-imidazo[1,2-a]pyridine, was successfully prepared with an iododestannylation reaction catalyzed by hydrogen peroxide. The modified thioflavin-T derivative displayed a good binding affinity for preformed synthetic Abeta40 aggregates in solution (K(i)=15+/-5 nM) and showed selective plaque labeling on postmortem AD brain sections. Biodistribution study in normal mice after an iv injection of [125I]IMPY exhibited excellent brain uptake (2.9% initial dose/brain at 2 min) and fast washout (0.2% initial dose/brain at 60 min). These properties are highly desirable for amyloid plaque imaging agents. In vivo plaque labeling was evaluated in a transgenic mouse model (Tg2576) engineered to produce excess amyloid plaques in the brain. Ex vivo autoradiograms of brain sections of the Tg 2576 mouse obtained at 4 h after an i.v. injection of [125I]IMPY clearly displayed a distinct plaque labeling with a low background activity. When the same brain section was stained with a fluorescent dye, thioflavin-S, the same Abeta plaques showed prominent fluorescent labeling consistent with the results of the autoradiogram. In conclusion, these findings clearly suggest that radioiodinated IMPY demonstrates desirable characteristics for in vivo labeling of Abeta plaques and it may be useful as a molecular imaging agent to study amyloidogenesis in the brain of living AD patients. Copyright 2002 Elsevier Science B.V.

Microglia Morphological Categorization in a Rat Model of Neuroinflammation by Hierarchical Cluster and Principal Components Analysis.

PubMed

Fernández-Arjona, María Del Mar; Grondona, Jesús M; Granados-Durán, Pablo; Fernández-Llebrez, Pedro; López-Ávalos, María D

2017-01-01

It is known that microglia morphology and function are closely related, but only few studies have objectively described different morphological subtypes. To address this issue, morphological parameters of microglial cells were analyzed in a rat model of aseptic neuroinflammation. After the injection of a single dose of the enzyme neuraminidase (NA) within the lateral ventricle (LV) an acute inflammatory process occurs. Sections from NA-injected animals and sham controls were immunolabeled with the microglial marker IBA1, which highlights ramifications and features of the cell shape. Using images obtained by section scanning, individual microglial cells were sampled from various regions (septofimbrial nucleus, hippocampus and hypothalamus) at different times post-injection (2, 4 and 12 h). Each cell yielded a set of 15 morphological parameters by means of image analysis software. Five initial parameters (including fractal measures) were statistically different in cells from NA-injected rats (most of them IL-1β positive, i.e., M1-state) compared to those from control animals (none of them IL-1β positive, i.e., surveillant state). However, additional multimodal parameters were revealed more suitable for hierarchical cluster analysis (HCA). This method pointed out the classification of microglia population in four clusters. Furthermore, a linear discriminant analysis (LDA) suggested three specific parameters to objectively classify any microglia by a decision tree. In addition, a principal components analysis (PCA) revealed two extra valuable variables that allowed to further classifying microglia in a total of eight sub-clusters or types. The spatio-temporal distribution of these different morphotypes in our rat inflammation model allowed to relate specific morphotypes with microglial activation status and brain location. An objective method for microglia classification based on morphological parameters is proposed. Main points Microglia undergo a quantifiable morphological change upon neuraminidase induced inflammation.Hierarchical cluster and principal components analysis allow morphological classification of microglia.Brain location of microglia is a relevant factor.

Microglia Morphological Categorization in a Rat Model of Neuroinflammation by Hierarchical Cluster and Principal Components Analysis

PubMed Central

Fernández-Arjona, María del Mar; Grondona, Jesús M.; Granados-Durán, Pablo; Fernández-Llebrez, Pedro; López-Ávalos, María D.

2017-01-01

It is known that microglia morphology and function are closely related, but only few studies have objectively described different morphological subtypes. To address this issue, morphological parameters of microglial cells were analyzed in a rat model of aseptic neuroinflammation. After the injection of a single dose of the enzyme neuraminidase (NA) within the lateral ventricle (LV) an acute inflammatory process occurs. Sections from NA-injected animals and sham controls were immunolabeled with the microglial marker IBA1, which highlights ramifications and features of the cell shape. Using images obtained by section scanning, individual microglial cells were sampled from various regions (septofimbrial nucleus, hippocampus and hypothalamus) at different times post-injection (2, 4 and 12 h). Each cell yielded a set of 15 morphological parameters by means of image analysis software. Five initial parameters (including fractal measures) were statistically different in cells from NA-injected rats (most of them IL-1β positive, i.e., M1-state) compared to those from control animals (none of them IL-1β positive, i.e., surveillant state). However, additional multimodal parameters were revealed more suitable for hierarchical cluster analysis (HCA). This method pointed out the classification of microglia population in four clusters. Furthermore, a linear discriminant analysis (LDA) suggested three specific parameters to objectively classify any microglia by a decision tree. In addition, a principal components analysis (PCA) revealed two extra valuable variables that allowed to further classifying microglia in a total of eight sub-clusters or types. The spatio-temporal distribution of these different morphotypes in our rat inflammation model allowed to relate specific morphotypes with microglial activation status and brain location. An objective method for microglia classification based on morphological parameters is proposed. Main points Microglia undergo a quantifiable morphological change upon neuraminidase induced inflammation.Hierarchical cluster and principal components analysis allow morphological classification of microglia.Brain location of microglia is a relevant factor. PMID:28848398

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

A new rabbit model for the study of early brain injury after subarachnoid hemorrhage.

PubMed

Marbacher, Serge; Andereggen, Lukas; Neuschmelting, Volker; Widmer, Hans Rudolf; von Gunten, Michael; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2012-07-15

Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells. SAH was performed using an extra-intracranial blood shunt. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional cerebral blood flow (rCBF) were continuously measured. Apoptosis and neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively. ICP increase caused a CPP decrease to almost zero (8±5mmHg) and decreases in left and right rCBF to 23±8% and 19±9% of their baseline values. TUNEL- and FJB-stained sections revealed significant apoptosis and neurodegeneration in both basal cortex and hippocampal regions compared to sham-operated animals. The apoptotic index in basilar artery endothelial cells was 74%±11%. The blood shunt rabbit SAH model elicits acute physiological dearrangements and provokes marked and consistent early damage to the hippocampus, basal cortex, and cerebral vasculature 24h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Cytosolic labile zinc: a marker for apoptosis in the developing rat brain.

PubMed

Lee, Joo-Yong; Hwang, Jung Jin; Park, Mi-Ha; Koh, Jae-Young

2006-01-01

Cytosolic zinc accumulation was thought to occur specifically in neuronal death (necrosis) following acute injury. However, a recent study demonstrated that zinc accumulation also occurs in adult rat neurons undergoing apoptosis following target ablation, and in vitro experiments have shown that zinc accumulation may play a causal role in various forms of apoptosis. Here, we examined whether intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis during development. Embryonic and newborn Sprague-Dawley rat brains were double-stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) detection of apoptosis and immunohistochemical detection of stage-specific neuronal markers, such as nestin, proliferating cell nuclear antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results revealed that apoptotic cell death occurred in neurons of diverse stages (neural stem cells, and dividing, young and adult neurons) throughout the brain during the embryonic and early postnatal periods. Further staining of brain sections with acid fuchsin or zinc-specific fluorescent dyes showed that all of the apoptotic neurons were acidophilic and contained labile zinc in their cell bodies. Cytosolic zinc accumulation was also observed in cultured cortical neurons undergoing staurosporine- or sodium nitroprusside (SNP)-induced apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) reduced SNP-induced apoptosis but not staurosporine-induced apoptosis, indicating that cytosolic zinc accumulation does not play a causal role in all forms of apoptosis. Finally, the specific cytosolic zinc accumulation may have a practical application as a relatively simple marker for neurons undergoing developmental apoptosis.

Preliminary report on macroscopic age changes in the human prosencephalon. A stereologic investigation.

PubMed

Eggers, R; Haug, H; Fischer, D

1984-01-01

The studies here reported were performed on the prosencephalons of 12 human brains between 37 and 86 years of age having no signs of neuropathological alteration. The evaluation was carried out on serial frontal sections with a mean thickness of 5 mm with stereological point counting procedures for volume and surface area. The results were mainly given in relative values since the range of variation is very high and the sample small. The aging process was evaluated with the aid of a linear regression function. The stereological investigation regarding the absolute values of volume and surface area (border face) of the macroscopical brain parts show a high interindividual variability. However, the relative volume of brain parts shows only small variations. Changes during aging could consequently only be revealed with the help of the relative values. The relative volumes and surface areas of the frontal lobe and the prosencephalic ganglia decrease with aging, while the parieto-occipital lobe and the striate cortex increase. However, if we refer these relative increases to the absolute decrease of brain volume, corresponding changes cannot be found in the parieto-occipital lobe until old age. The shrinkage of the frontal lobe, of the centrum semiovale and of the prosencephalic ganglia exceeds 10%. In the grays it is probably accompanied by a loss of neurons. The relative sizes of the surface area do not change significantly during aging with exception of the frontal cortex. The thickness of the cortex remains probably constant. The size of lateral ventricles increases with aging.

Detection of a Novel Bovine Astrovirus in a Cow with Encephalitis.

PubMed

Schlottau, K; Schulze, C; Bilk, S; Hanke, D; Höper, D; Beer, M; Hoffmann, B

2016-06-01

Encephalitis can be caused by several infectious agents, including bacteria, fungi, parasites and viruses. In many cases, the causative agent cannot be identified, because the pathogens are unknown or detection methods are not routinely available. In our case, a 15-month-old cow developed central nervous disorders and died within 6 days after the onset of clinical signs. The histopathology revealed an acute encephalitis, predominantly in the brain stem, and a ganglionitis of the trigeminal ganglion with massive neuronal necroses in both the brain and the ganglion. However, a relevant panel of bacterial and viral infections of cattle could be routinely excluded. Therefore, a brain sample from the cow was analysed using a metagenomics approach with next-generation sequencing. A novel bovine astrovirus (BoAstV-BH89/14) could be identified using the analysis pipeline RIEMS, and the finding could be confirmed with a specific BoAstV RT-qPCR. The genome of the bovine astrovirus (BoAstV), belonging to the family Astroviridae in the genus Mamastrovirus, has a length of 6478 bp. Sequence identities between 71% to a sheep astrovirus and 69% to two recently described bovine astroviruses from the USA and Switzerland were ascertained. The latter were also connected to encephalitis cases in cattle. Like these, the new virus described here was detected in different brain sections using the specific BoAstV RT-qPCR and fluorescent in situ hybridization. In conclusion, while astroviruses so far were mainly found in relation to gastroenteritis in animals and humans, recently detected astrovirus infections were also related to encephalitis. © 2016 Blackwell Verlag GmbH.

Increased gray matter density in the parietal cortex of mathematicians: a voxel-based morphometry study.

PubMed

Aydin, K; Ucar, A; Oguz, K K; Okur, O O; Agayev, A; Unal, Z; Yilmaz, S; Ozturk, C

2007-01-01

The training to acquire or practicing to perform a skill, which may lead to structural changes in the brain, is called experience-dependent structural plasticity. The main purpose of this cross-sectional study was to investigate the presence of experience-dependent structural plasticity in mathematicians' brains, which may develop after long-term practice of mathematic thinking. Twenty-six volunteer mathematicians, who have been working as academicians, were enrolled in the study. We applied an optimized method of voxel-based morphometry in the mathematicians and the age- and sex-matched control subjects. We assessed the gray and white matter density differences in mathematicians and the control subjects. Moreover, the correlation between the cortical density and the time spent as an academician was investigated. We found that cortical gray matter density in the left inferior frontal and bilateral inferior parietal lobules of the mathematicians were significantly increased compared with the control subjects. Furthermore, increase in gray matter density in the right inferior parietal lobule of the mathematicians was strongly correlated with the time spent as an academician (r = 0.84; P < .01). Left-inferior frontal and bilateral parietal regions are involved in arithmetic processing. Inferior parietal regions are also involved in high-level mathematic thinking, which requires visuospatial imagery, such as mental creation and manipulation of 3D objects. The voxel-based morphometric analysis of mathematicians' brains revealed increased gray matter density in the cortical regions related to mathematic thinking. The correlation between cortical density increase and the time spent as an academician suggests experience-dependent structural plasticity in mathematicians' brains.

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents

PubMed Central

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A.; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-01-01

Objectives Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Materials and Methods Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. Results No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis–like skin lesions. The Gd concentrations observed in the skin/brain samples (in nanomole Gd per gram of tissue) for each agent were as follows: gadodiamide: 1472 ± 115/11.1 ± 5.1, gadopentetate dimeglumine: 80.8 ± 6.2/13.1 ± 7.3, gadobutrol: 1.1 ± 0.5/0.7 ± 0.4, and gadoteridol: 1.7 ± 0.8/0.5 ± 0.2. The average detected residual Gd concentration in the brain was approximately 15-fold higher for linear than for macrocyclic GBCAs. The highest amounts of Gd found in brain corresponded to less than 0.0002% of the injected dose per gram of tissue. Using LA-ICP-MS, high Gd concentrations in the deep cerebellar nuclei and in the granular layer of the cerebellar cortex were detected only for linear gadodiamide and gadopentetate dimeglumine but not for gadoteridol or gadobutrol. The energy dispersive x-ray spectroscopy analysis revealed Gd-containing spots in the skin of animals administered gadodiamide and gadopentetate dimeglumine. Transmission electron microscopy revealed several Gd-containing spots in the region of the dentate nuclei in the brain of 1 animal injected with gadodiamide. Conclusions After repeated high dosing, nephrogenic systemic fibrosis–like macroscopic and histopathological lesions of the skin were observed only in some of the gadodiamide-treated animals. No histopathological findings were detected in the rodent brain. The administration of linear GBCAs was associated with significantly higher Gd concentrations in the brain and skin compared with macrocyclic GBCA administration. The results of LA-ICP-MS demonstrated local accumulation of Gd within the deep cerebellar nuclei and the granular layer only after the administration of linear agents. In summary, the detected low Gd concentrations in the skin and brain were well correlated with the higher kinetic stability of macrocyclic GBCA. PMID:28323657

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-06-01

Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis-like skin lesions. The Gd concentrations observed in the skin/brain samples (in nanomole Gd per gram of tissue) for each agent were as follows: gadodiamide: 1472 ± 115/11.1 ± 5.1, gadopentetate dimeglumine: 80.8 ± 6.2/13.1 ± 7.3, gadobutrol: 1.1 ± 0.5/0.7 ± 0.4, and gadoteridol: 1.7 ± 0.8/0.5 ± 0.2. The average detected residual Gd concentration in the brain was approximately 15-fold higher for linear than for macrocyclic GBCAs. The highest amounts of Gd found in brain corresponded to less than 0.0002% of the injected dose per gram of tissue. Using LA-ICP-MS, high Gd concentrations in the deep cerebellar nuclei and in the granular layer of the cerebellar cortex were detected only for linear gadodiamide and gadopentetate dimeglumine but not for gadoteridol or gadobutrol. The energy dispersive x-ray spectroscopy analysis revealed Gd-containing spots in the skin of animals administered gadodiamide and gadopentetate dimeglumine. Transmission electron microscopy revealed several Gd-containing spots in the region of the dentate nuclei in the brain of 1 animal injected with gadodiamide. After repeated high dosing, nephrogenic systemic fibrosis-like macroscopic and histopathological lesions of the skin were observed only in some of the gadodiamide-treated animals. No histopathological findings were detected in the rodent brain. The administration of linear GBCAs was associated with significantly higher Gd concentrations in the brain and skin compared with macrocyclic GBCA administration. The results of LA-ICP-MS demonstrated local accumulation of Gd within the deep cerebellar nuclei and the granular layer only after the administration of linear agents. In summary, the detected low Gd concentrations in the skin and brain were well correlated with the higher kinetic stability of macrocyclic GBCA.

Functional magnetic resonance imaging reflects changes in brain functioning with sedation.

PubMed

Starbuck, Victoria N; Kay, Gary G; Platenberg, R. Craig; Lin, Chin-Shoou; Zielinski, Brandon A

2000-12-01

Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd.

[A Case of Transorbital Penetrating Brain Injury Caused by a Steel Wire Entirely Embedded in the Brain Parenchyma].

PubMed

Kin, Kyohei; Ono, Yasuhiro; Fujimori, Takeshi; Kuramoto, Satoshi; Katsumata, Atsushi; Goda, Yuji; Kawauchi, Masamitsu

2015-10-01

Penetrating brain injury(PBI)is very rare in Japan. Because there is a very wide variety of pathological condition of PBI, the guideline for the treatment of PBI has not been established yet. We report the unique case of PBI caused by a steel wire piece completely embedded in the brain parenchyma. A 75-year-old man was brought to the emergency department due to ocular injury caused by a steel wire piece. Neurological examination revealed only left visual disturbance. CT scan revealed a steel wire piece located intraparenchymally between the left frontal lobe and the ventricles, but digital subtraction angiography showed no significant vascular injury in the surrounding structures. We performed an open surgery and removed the steel wire piece. Because the steel wire piece was completely embedded in the brain, we used intraoperative X-ray fluoroscopy to choose a less invasive approach for the brain. The patient suffered no additional neurological deficit and no sign of cerebral infection or seizure after surgery. He was discharged after a 4-week administration of antibiotics. In most cases of PBI caused by low velocity injury, foreign bodies are not completely embedded in the brain except for remnants after surgical removal. This is the first report of low velocity PBI caused by a foreign body completely embedded in the brain.

Time-Frequency Cross Mutual Information Analysis of the Brain Functional Networks Underlying Multiclass Motor Imagery.

PubMed

Gong, Anmin; Liu, Jianping; Chen, Si; Fu, Yunfa

2018-01-01

To study the physiologic mechanism of the brain during different motor imagery (MI) tasks, the authors employed a method of brain-network modeling based on time-frequency cross mutual information obtained from 4-class (left hand, right hand, feet, and tongue) MI tasks recorded as brain-computer interface (BCI) electroencephalography data. The authors explored the brain network revealed by these MI tasks using statistical analysis and the analysis of topologic characteristics, and observed significant differences in the reaction level, reaction time, and activated target during 4-class MI tasks. There was a great difference in the reaction level between the execution and resting states during different tasks: the reaction level of the left-hand MI task was the greatest, followed by that of the right-hand, feet, and tongue MI tasks. The reaction time required to perform the tasks also differed: during the left-hand and right-hand MI tasks, the brain networks of subjects reacted promptly and strongly, but there was a delay during the feet and tongue MI task. Statistical analysis and the analysis of network topology revealed the target regions of the brain network during different MI processes. In conclusion, our findings suggest a new way to explain the neural mechanism behind MI.

The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea.

PubMed

Sasidharan, Vidyanand; Marepally, Srujan; Elliott, Sarah A; Baid, Srishti; Lakshmanan, Vairavan; Nayyar, Nishtha; Bansal, Dhiru; Sánchez Alvarado, Alejandro; Vemula, Praveen Kumar; Palakodeti, Dasaradhi

2017-09-15

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is crucial for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family ( miR-124 ) is highly conserved in animals and regulates neurogenesis by facilitating neural differentiation, yet its role in neural wiring and brain organization is not known. We developed a novel method for delivering anti-miRs using liposomes for the functional knockdown of microRNAs. Smed-miR-124 knockdown revealed a key role for these microRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1 , which encodes an axon guidance protein, either by targeting slit-1 mRNA or, potentially, by modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system. © 2017. Published by The Company of Biologists Ltd.

The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea

PubMed Central

Sasidharan, Vidyanand; Marepally, Srujan; Elliott, Sarah A.; Baid, Srishti; Lakshmanan, Vairavan; Nayyar, Nishtha; Bansal, Dhiru; Sánchez Alvarado, Alejandro; Vemula, Praveen Kumar

2017-01-01

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is crucial for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family (miR-124) is highly conserved in animals and regulates neurogenesis by facilitating neural differentiation, yet its role in neural wiring and brain organization is not known. We developed a novel method for delivering anti-miRs using liposomes for the functional knockdown of microRNAs. Smed-miR-124 knockdown revealed a key role for these microRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1, which encodes an axon guidance protein, either by targeting slit-1 mRNA or, potentially, by modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system. PMID:28807895

Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

PubMed Central

Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

2016-01-01

Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

Scedosporium apiospermum causing brain abscess in a renal allograft recipient.

PubMed

Sharma, Amit; Singh, Divya

2015-11-01

Scedosporium apiospermum is the asexual form of a rare fungus Pseudallescheria boydii that is usually present in the soil, sewage and dirty water. In immunocompromised patients, it is a rare infection involving multiple organs. We present a case of renal allograft recipient who developed fever two weeks post renal transplant. He was initially found to have dengue fever. After five days, he became drowsy and developed right-sided hemiparesis. Magnetic resonance imaging of the brain revealed multiple irregular masses with associated edema consistent with fungal brain abscesses. Left parietal abscess was drained and he was started on voriconazole. His cyclosporine was stopped. Drained pus revealed fungal hyphae on potassium hydroxide stain and Scedosporium apiospermum on culture. Unfortunately, the patient died after five days. Scedosporium infections should be kept as a possibility in transplant recipients with disseminated infections, especially with a brain abscess. Despite antifungal therapy and surgical drainage, mortality rates are high.

Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior.

PubMed

Portugues, Ruben; Feierstein, Claudia E; Engert, Florian; Orger, Michael B

2014-03-19

Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate but ordered pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments systematically reveal the functional architecture of neural circuits underlying a sensorimotor behavior in a vertebrate brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Complexity of EEG-signal in Time Domain - Possible Biomedical Application

NASA Astrophysics Data System (ADS)

Klonowski, Wlodzimierz; Olejarczyk, Elzbieta; Stepien, Robert

2002-07-01

Human brain is a highly complex nonlinear system. So it is not surprising that in analysis of EEG-signal, which represents overall activity of the brain, the methods of Nonlinear Dynamics (or Chaos Theory as it is commonly called) can be used. Even if the signal is not chaotic these methods are a motivating tool to explore changes in brain activity due to different functional activation states, e.g. different sleep stages, or to applied therapy, e.g. exposure to chemical agents (drugs) and physical factors (light, magnetic field). The methods supplied by Nonlinear Dynamics reveal signal characteristics that are not revealed by linear methods like FFT. Better understanding of principles that govern dynamics and complexity of EEG-signal can help to find `the signatures' of different physiological and pathological states of human brain, quantitative characteristics that may find applications in medical diagnostics.

Analysis of microdissected neurons by 18O mass spectrometry reveals altered protein expression in Alzheimer's disease

PubMed Central

Hashimoto, Masakazu; Bogdanovic, Nenad; Nakagawa, Hiroyuki; Volkmann, Inga; Aoki, Mikio; Winblad, Bengt; Sakai, Jun; Tjernberg, Lars O

2012-01-01

Abstract It is evident that the symptoms of Alzheimer's disease (AD) are derived from severe neuronal damage, and especially pyramidal neurons in the hippocampus are affected pathologically. Here, we analysed the proteome of hippocampal neurons, isolated from post-mortem brains by laser capture microdissection. By using 18O labelling and mass spectrometry, the relative expression levels of 150 proteins in AD and controls were estimated. Many of the identified proteins are involved in transcription and nucleotide binding, glycolysis, heat-shock response, microtubule stabilization, axonal transport or inflammation. The proteins showing the most altered expression in AD were selected for immunohistochemical analysis. These analyses confirmed the altered expression levels, and showed in many AD cases a pathological pattern. For comparison, we also analysed hippocampal sections by Western blot. The expression levels found by this method showed poor correlation with the neuron-specific analysis. Hence, we conclude that cell-specific proteome analysis reveals differences in the proteome that cannot be detected by bulk analysis. PMID:21883897

Social risky decision-making reveals gender differences in the TPJ: A hyperscanning study using functional near-infrared spectroscopy.

PubMed

Zhang, Mingming; Liu, Tao; Pelowski, Matthew; Jia, Huibin; Yu, Dongchuan

2017-12-01

Previous neuroscience studies have investigated neural correlates of risky decision-making in a single-brain frame during pseudo social (predominantly non face-to-face) contexts. To fully understand the risky decision-making behavior in more natural social interactions, the present study employed a functional near-infrared spectroscopy (fNIRS) hyperscanning technique to simultaneously measure pairs of participants' fronto-temporal activations in a face-to-face gambling card-game. The intra-brain results revealed that both those who identified as males and as females showed higher activations in their mPFC and in the inferior parts of the frontopolar area, as well as in the tempo-parietal junction (TPJ) in cases involving higher versus lower risk. This is consistent with previous findings suggesting importance of the mentalizing network in decision tasks. The fNIRS results of inter-brain neural synchronization (INS) also revealed that males and females showed increased inter-brain coherence in the mPFC and dlPFC. Females, however, uniquely showed increased inter-brain coherence in the left TPJ. This INS result suggests that males may primarily depend on non-social cognitive ability to make a risky decision in a social interaction, while females may use both social and non-social cognitive abilities. The implications are also discussed for general topics of human interaction and two-person neuroscience. Copyright © 2017 Elsevier Inc. All rights reserved.

Students with Acquired Brain Injury. The School's Response.

ERIC Educational Resources Information Center

Glang, Ann, Ed.; Singer, George H. S., Ed.; Todis, Bonnie, Ed.

Designed for educators, this book focuses on educational issues relating to students with acquired brain injury (ABI), and describes approaches that have been effective in improving the school experiences of students with brain injury. Section 1 provides an introduction to issues related to ABI in children and youth and includes: "An Overview of…

A Novel Application for the Cavalieri Principle: A Stereological and Methodological Study

PubMed Central

Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin

2009-01-01

Objective The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. Materials and Methods In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. Results There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). Conclusion This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method. PMID:25610077

A novel application for the cavalieri principle: a stereological and methodological study.

PubMed

Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin

2009-08-01

The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method.

Combining Fiber Dissection, Plastination, and Tractography for Neuroanatomical Education: Revealing the Cerebellar Nuclei and Their White Matter Connections

ERIC Educational Resources Information Center

Arnts, Hisse; Kleinnijenhuis, Michiel; Kooloos, Jan G. M.; Schepens-Franke, Annelieke N.; van Cappellen van Walsum, Anne-Marie

2014-01-01

In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpretation of clinical and imaging data on white…

Annual Research Review: The Promise of Stem Cell Research for Neuropsychiatric Disorders

ERIC Educational Resources Information Center

Vaccarino, Flora M.; Urban, Alexander Eckehart; Stevens, Hanna E.; Szekely, Anna; Abyzov, Alexej; Grigorenko, Elena L.; Gerstein, Mark; Weissman, Sherman

2011-01-01

The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders,…

If You Had My Brain, Where Would I Be? Children's Understanding of the Brain and Identity.

ERIC Educational Resources Information Center

Johnson, Carl Nils

1990-01-01

Reveals that during the elementary school years, children acquire a firm understanding of the brain as the primary locus of psychological attributes and identity. The early school years, when children are five to seven years old, appear to be a transitional phase, when performance is variable and subject to task conditions. (RH)

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

2012-01-01

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

Voxel-based morphometry and fMRI revealed differences in brain gray matter in breastfed and milk formula–fed children

USDA-ARS?s Scientific Manuscript database

Background and Purpose: Infant diets may have significant impact on brain development in children. The aim of this study was to evaluate brain grey matter structure and function in 8-year-old children who were predominantly breastfed (BF) or fed cow’s milk formula (MF) as infants. Materials and Me...

Survivors of a Silent Epidemic: The Learning Experience of College Students with a History of Traumatic Brain Injury

ERIC Educational Resources Information Center

Schlessman, Heather A.

2010-01-01

A significant proportion of young adults experience a traumatic brain injury (TBI) every year, and students with this history are becoming a growing presence on college campuses. A review of the literature revealed very little research exploring the learning experiences of college students with a history of traumatic brain injury. The purpose of…

Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in Functional Patterns during Spoken Communications

PubMed Central

Tadić, Bosiljka; Andjelković, Miroslav; Boshkoska, Biljana Mileva; Levnajić, Zoran

2016-01-01

Human behaviour in various circumstances mirrors the corresponding brain connectivity patterns, which are suitably represented by functional brain networks. While the objective analysis of these networks by graph theory tools deepened our understanding of brain functions, the multi-brain structures and connections underlying human social behaviour remain largely unexplored. In this study, we analyse the aggregate graph that maps coordination of EEG signals previously recorded during spoken communications in two groups of six listeners and two speakers. Applying an innovative approach based on the algebraic topology of graphs, we analyse higher-order topological complexes consisting of mutually interwoven cliques of a high order to which the identified functional connections organise. Our results reveal that the topological quantifiers provide new suitable measures for differences in the brain activity patterns and inter-brain synchronisation between speakers and listeners. Moreover, the higher topological complexity correlates with the listener’s concentration to the story, confirmed by self-rating, and closeness to the speaker’s brain activity pattern, which is measured by network-to-network distance. The connectivity structures of the frontal and parietal lobe consistently constitute distinct clusters, which extend across the listener’s group. Formally, the topology quantifiers of the multi-brain communities exceed the sum of those of the participating individuals and also reflect the listener’s rated attributes of the speaker and the narrated subject. In the broader context, the presented study exposes the relevance of higher topological structures (besides standard graph measures) for characterising functional brain networks under different stimuli. PMID:27880802

Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity evaluation.

PubMed

O'Callaghan, James P; Daughtrey, Wayne C; Clark, Charles R; Schreiner, Ceinwen A; White, Russell

2014-11-01

Sprague-Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) and exposures were for 6h/day, 5days/week for 13weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiplebrain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration. Copyright © 2014 Elsevier Inc. All rights reserved.

Focal attenuation of specific electroencephalographic power over the right parahippocampal region during transcerebral copper screening in living subjects and hemispheric asymmetric voltages in fixed brain tissue.

PubMed

Rouleau, Nicolas; Lehman, Brendan; Persinger, Michael A

2016-08-01

Covering the heads of human volunteers with a toque lined with copper mesh compared to no mesh resulted in significant diminishments in quantitative electroencephalographic power within theta and beta-gamma bands over the right caudal hemisphere. The effect was most evident in women compared to men. The significant attenuation of power was verified by LORETA (low resolution electromagnetic tomography) within the parahippocampal region of the right hemisphere. Direct measurements of frequency-dependent voltages of coronal section preserved in ethanol-formalin-acetic acid from our human brain collection revealed consistently elevated power (0.2μV(2)Hz(-1)) in right hemispheric structures compared to left. The discrepancy was most pronounced in the grey (cortical) matter of the right parahippocampal region. Probing the superficial convexities of the cerebrum in an unsectioned human brain demonstrated rostrocaudal differences in hemispheric spectral power density asymmetries, particularly over caudal and parahippocampal regions, which were altered as a function of the chemical and spatial contexts imposed upon the tissue. These results indicate that the heterogeneous response of the human cerebrum to covering of the head by a thin conductor could reflect an intrinsic structure and unique electrical property of the (entorhinal) cortices of the right caudal hemisphere that persists in fixed tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

Correlation Between Extravasation and Alterations of Cerebrovascular Laminin and β-Dystroglycan Immunoreactivity Following Cryogenic Lesions in Rats.

PubMed

Kálmán, Mihály; Tóth, László; Szöllosi, Dávid; Oszwald, Erzsébet; Mahalek, Judit; Sadeghian, Sam

2017-11-01

The blood-brain barrier becomes "leaky" following lesions. Former studies revealed that following lesions the immunoreactivity of cerebrovascular laminin becomes detectable whereas that of β-dystroglycan disappears. These alterations may be indicators of glio-vascular decoupling that may result in the impairment of the blood-brain-barrier. This study investigates correlation between the post-lesion extravasation and the above-mentioned immunohistochemical alterations. Following cryogenic lesions, the survival periods lasted 5, 10, 30 minutes, 1 or 12 hours, or 1 day. Some brains were fixed immediately post-lesion. Immunofluorescent reactions were performed in floating sections. The extravasation was detected with immunostaining for plasma fibronectin and rat immunoglobulins. When the survival period was 30 minutes or longer, the area of extravasation corresponded to the area of altered laminin and β-dystroglycan immunoreactivities. Following immediate fixation some laminin immunoreactivity was already detected. The extravasation seemed to precede this early appearance of laminin immunoreactivity. The β-dystroglycan immunoreactivity disappeared later. When the extravasation spread into the corpus callosum, vascular laminin immunoreactivity appeared but the β-dystroglycan immunoreactivity persisted. It seems that extravasation separates the glial and vascular basal laminae, which results in the appearance of laminin immunoreactivity. The disappearance of β-dystroglycan immunoreactivity is neither a condition nor an inevitable consequence of the 2 other phenomena. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Positron emission tomography reveals correlations between brain metabolism and mood changes in hyperthyroidism.

PubMed

Schreckenberger, M F; Egle, U T; Drecker, S; Buchholz, H G; Weber, M M; Bartenstein, P; Kahaly, G J

2006-12-01

Hyperthyroidism is frequently associated with emotional distress. The underlying cerebral processes of the endocrine-induced mood changes are unclear. The objective of this study was to investigate, for the first time, the neuronal correlates of thyrotoxicosis-associated psychic symptoms using positron emission tomography (PET). The study was designed as a cross-sectional trial. The study was performed at joint nuclear medicine and thyroid clinics. Twelve patients with untreated Graves' hyperthyroidism were evaluated. Levels of emotional distress were self-rated by means of the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender-matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan. Subsequently, the functional relationship between brain metabolism and the psychometric scores was analyzed. Compared with controls and visualized by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001) glucose metabolism in the limbic system (uncus and inferior temporal gyrus). Activation foci in the posterior cingulate and in the inferior parietal lobe were correlated with both anxiety and depression scales (P < 0.001). Compared with patients with normal anxiety levels, those with increased anxiety yielded an enhanced glucose metabolism (P < 0.001) in the bilateral sensory association cortex. Serum free T3/free T4 levels negatively correlated with regional glucose metabolism in the medial posterior cingulate. Thyrotoxicosis and associated psychic symptoms are correlated to regional metabolic changes in the main structures of the limbic/paralimbic system.

Nuclear organisation of some immunohistochemically identifiable neural systems in five species of insectivore-Crocidura cyanea, Crocidura olivieri, Sylvisorex ollula, Paraechinus aethiopicus and Atelerix frontalis.

PubMed

Calvey, Tanya; Patzke, Nina; Bennett, Nigel C; Consolate, Kaswera-Kyamakya; Gilissen, Emmanuel; Alagaili, Abdulaziz N; Mohammed, Osama B; Pettigrew, John D; Manger, Paul R

2016-03-01

The organization of the cholinergic, catecholaminergic, and serotonergic neurons in the brains of five species of insectivores and the orexinergic (hypocretinergic) system in four insectivore species is presented. We aimed to investigate the nuclear complement of these neural systems in comparison to those of other mammalian species. Brains of insectivores were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei were similar among the species investigated and to mammals in general, but certain differences in the nuclear complement highlighted potential phylogenetic interrelationships. In the cholinergic system, the three shrew species lacked parabigeminal and Edinger-Westphal nuclei. In addition, the appearance of the laterodorsal tegmental nucleus in all insectivores revealed a mediodorsal arch. All three of these features are the same as those present in microchiropterans. The catecholaminergic system of the three shrew species lacked the A4 and A15d nuclei, as well as having an incipient A9v nucleus, again features found in microchiropteran brains. The serotonergic and orexinergic systems of the insectivores are similar to those seen across most eutherian mammals. The analysis of similarities and differences across mammalian species indicates a potential phylogenetic relationship between the Soricidae (shrews) and the microchiropterans. Copyright © 2015 Elsevier B.V. All rights reserved.

Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity

PubMed Central

Giles, James A; Greenhalgh, Andrew D; Davies, Claire L; Denes, Adam; Shaw, Tovah; Coutts, Graham; Rothwell, Nancy J; McColl, Barry W; Allan, Stuart M

2015-01-01

The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders. PMID:25367678

Optical mapping of brain activation during the English to Chinese and Chinese to English sight translation

PubMed Central

He, Yan; Wang, Meng-Yun; Li, Defeng; Yuan, Zhen

2017-01-01

Translating from Chinese into another language or vice versa is becoming a widespread phenomenon. However, current neuroimaging studies are insufficient to reveal the neural mechanism underlying translation asymmetry during Chinese/English sight translation. In this study, functional near infrared spectroscopy (fNIRS) was used to extract the brain activation patterns associated with Chinese/English sight translation. Eleven unbalanced Chinese (L1)/English (L2) bilinguals participated in this study based on an intra-group experimental design, in which two translation and two reading aloud tasks were administered: forward translation (from L1 to L2), backward translation (from L2 to L1), L1 reading, and L2 reading. As predicted, our findings revealed that forward translation elicited more pronounced brain activation in Broca’s area, suggesting that neural correlates of translation vary according to the direction of translation. Additionally, significant brain activation in the left PFC was involved in backward translation, indicating the importance of this brain region during the translation process. The identical activation patterns could not be discovered in forward translation, indicating the cognitive processing of reading logographic languages (i.e. Chinese) might recruit incongruent brain regions. PMID:29296476

Leaping from brain to mind: a critique of mirror neuron explanations of countertransference.

PubMed

Vivona, Jeanine M

2009-06-01

In the current vigorous debate over the value of neuroscience to psychoanalysis, the epistemological status of the links between the data of brain research and the constructs of interest to psychoanalysts has rarely been examined. An inspection of recent discussions of mirror neuron research, particularly regarding countertransference, reveals gaps between psychoanalytic processes and the available brain activation data, and allows the evaluation of evidence for three implicit assumptions frequently made to bridge these gaps: (1) there is a straightforward correspondence between observed brain activity and mental activity; (2) similarity of localized brain activity across individuals signifies a shared interpersonal experience; (3) an automatic brain mechanism enables direct interpersonal sharing of experiences in the absence of inference and language. Examination of mirror neuron research findings reveals that these assumptions are either untested or questionable. Moreover, within neuroscience there are competing interpretations of mirror neuron findings, with diverse implications for psychoanalysis. The present state of mirror neuron research may offer us new hypotheses or metaphors, but does not provide empirical validation of the proposed models. More generally, as we attempt to learn from research findings generated outside psychoanalysis, we must strive to think scientifically, by minding the difference between data and interpretation.

Detailed longitudinal sampling of glioma stem cells in situ reveals Chr7 gain and Chr10 loss as repeated events in primary tumor formation and recurrence.

PubMed

Baysan, Mehmet; Woolard, Kevin; Cam, Margaret C; Zhang, Wei; Song, Hua; Kotliarova, Svetlana; Balamatsias, Demosthenes; Linkous, Amanda; Ahn, Susie; Walling, Jennifer; Belova, Galina I; Fine, Howard A

2017-11-15

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. © 2017 UICC.

Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

PubMed Central

Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed cell proliferation may evolve into more severe neurodegenerative diseases and psychiatric disorders currently being recognized in traumatized TBI patients. PMID:24349091

Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics.

PubMed

Becker, J Sabine; Matusch, Andreas; Palm, Christoph; Salber, Dagmar; Morton, Kathryn A; Becker, J Susanne

2010-02-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.

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

PubMed Central

2014-01-01

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

75 FR 51081 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

...- 0684, [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Brain Injury and Neurovascular Pathologies Study Section. Date: September 27-28, 2010. Time...

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

PubMed

Nishiyama, Yuichi; Kanayama, Hidekazu; Mori, Hiroshi; Tada, Keiji; Yamamoto, Yasushi; Katsube, Takashi; Takeshita, Haruo; Kawakami, Kazunori; Kitagaki, Hajime

2017-06-01

This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

Meningoencephalitis due to the amoeboflagellate Naegleria fowleri in ruminants in Algeria.

PubMed

Benterki, Mohamed Seghir; Ayachi, Ammar; Bennoune, Omar; Régoudis, Estelle; Pélandakis, Michel

2016-01-01

Primary amoebic meningoencephalitis (PAM) is a fatal infection in most cases, caused by the amoeba flagellate Naegleria fowleri. This report describes the first cases of PAM in Algeria, in a cow and a ewe from Batna, north-eastern Algeria. The death of both ruminants occurred a week after the first clinical manifestations. The cerebrospinal fluid, after staining with May-Grünwald-Giemsa, showed the presence of amoebae cells. Histological sections revealed numerous amoebae in all parts of the brain. The presence of N. fowleri was confirmed using a species-specific real-time PCR in histological tissue sections. The two PAM cases were reported during the hot season, and the source of infection is very likely the water where the cattle came to drink. Particular attention should be focused on this type of infection in aquatic environments when the temperature is high and preventive measures must be taken to avoid the proliferation of N. fowleri. © M. Benterki et al., published by EDP Sciences, 2016.

Meningoencephalitis due to the amoeboflagellate Naegleria fowleri in ruminants in Algeria

PubMed Central

Benterki, Mohamed Seghir; Ayachi, Ammar; Bennoune, Omar; Régoudis, Estelle; Pélandakis, Michel

2016-01-01

Primary amoebic meningoencephalitis (PAM) is a fatal infection in most cases, caused by the amoeba flagellate Naegleria fowleri. This report describes the first cases of PAM in Algeria, in a cow and a ewe from Batna, north-eastern Algeria. The death of both ruminants occurred a week after the first clinical manifestations. The cerebrospinal fluid, after staining with May-Grünwald-Giemsa, showed the presence of amoebae cells. Histological sections revealed numerous amoebae in all parts of the brain. The presence of N. fowleri was confirmed using a species-specific real-time PCR in histological tissue sections. The two PAM cases were reported during the hot season, and the source of infection is very likely the water where the cattle came to drink. Particular attention should be focused on this type of infection in aquatic environments when the temperature is high and preventive measures must be taken to avoid the proliferation of N. fowleri. PMID:26979770

Maternal Pseudo-Bartter Syndrome Associated with Severe Perinatal Brain Injury.

PubMed

Vora, Shrenik; Ibrahim, Thowfique; Rajadurai, Victor Samuel

2017-09-15

Maternal electrolyte imbalance is rarely reported as causative factor of severe perinatal brain injury. This case outlines a unique maternal and neonatal pseudo-Bartter syndrome presented with metabolic alkalosis and hypochloremia due to maternal severe vomiting. Neonatal MRI brain revealed extensive brain hemorrhages with porencephalic cysts. Subsequent investigation workup points towards maternal severe metabolic alkalosis as its cause. Careful medical attention should be paid to pregnant women with excessive vomiting to ensure a healthy outcome for both the mother and the baby.

[Factor structure of regional CBF and CMRglu values as a tool for the study of default mode of the brain].

PubMed

Kataev, G V; Korotkov, A D; Kireev, M V; Medvedev, S V

2013-01-01

In the present article it was shown that the functional connectivity of brain structures, revealed by factor analysis of resting PET CBF and rCMRglu data, is an adequate tool to study the default mode of the human brain. The identification of neuroanatomic systems of default mode (default mode network) during routine clinical PET investigations is important for further studying the functional organization of the normal brain and its reorganizations in pathological conditions.

Heavy Drinking in College Students Is Associated with Accelerated Gray Matter Volumetric Decline over a 2 Year Period

PubMed Central

Meda, Shashwath A.; Dager, Alecia D.; Hawkins, Keith A.; Tennen, Howard; Raskin, Sarah; Wood, Rebecca M.; Austad, Carol S.; Fallahi, Carolyn R.; Pearlson, Godfrey D.

2017-01-01

Background: Heavy and/or harmful alcohol use while in college is a perennial and significant public health issue. Despite the plethora of cross-sectional research suggesting deleterious effects of alcohol on the brain, there is a lack of literature investigating the longitudinal effects of alcohol consumption on the adolescent brain. We aim to probe the longitudinal effects of college drinking on gray matter change in students during this crucial neurodevelopmental period. Methods: Data were derived from the longitudinal Brain and Alcohol Research in College Students (BARCS) study of whom a subset underwent brain MRI scans at two time points 24 months apart. Students were young adults with a mean age at baseline of about 18.5 years. Based on drinking metrics assessed at both baseline and followup, subjects were classified as sustained abstainers/light drinkers (N = 45) or sustained heavy drinkers (N = 84) based on criteria established in prior literature. Gray matter volumetric change (GMV-c) maps were derived using the longitudinal DARTEL pipeline as implemented in SPM12. GMV-c maps were then subjected to a 1-sample and 2-sample t-test in SPM12 to determine within- and between-group GMV-c differences in drinking groups. Supplementary between-group differences were also computed at baseline only. Results: Within-group analysis revealed significant decline in GMV in both groups across the 2 year followup period. However, tissue loss in the sustained heavy drinking group was more significant, larger per region, and more widespread across regions compared to abstainers/light drinkers. Between-group analysis confirmed the above and showed a greater rate of GMV-c in the heavy drinking group in several brain regions encompassing inferior/medial frontal gyrus, parahippocampus, and anterior cingulate. Supplementary analyses suggest that some of the frontal differences existed at baseline and progressively worsened. Conclusion: Sustained heavy drinking while in college was associated with accelerated GMV decline in brain regions involved with executive functioning, emotional regulation, and memory, which are critical to everyday life functioning. Areas of significant GMV decreases also overlapped largely with brain reward and stress systems implicated in addictive behavior. PMID:29033801

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

PubMed Central

Luo, Wenjie; Liu, Wencheng; Hu, Xiaoyan; Hanna, Mary; Caravaca, April; Paul, Steven M.

2015-01-01

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies. PMID:26057852

Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging for selective visualization of tau protein fibrils in the Alzheimer's disease brain.

PubMed

Harada, Ryuichi; Okamura, Nobuyuki; Furumoto, Shozo; Yoshikawa, Takeo; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka

2014-02-01

Selective visualization of amyloid-β and tau protein deposits will help to understand the pathophysiology of Alzheimer's disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique. Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [(3)H]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-β (Aβ) and tau fibrils. In AD brain sections, BF-188 clearly stained Aβ and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-β and tau fibrils with high affinity (K i  < 10 nM). In addition, BF-188 showed an excellent blood-brain barrier permeability in mice. Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-β in the brain.

Clinical applications of modern imaging technology: stereo image formation and location of brain cancer

NASA Astrophysics Data System (ADS)

Wang, Dezong; Wang, Jinxiang

1994-05-01

It is very important to locate the tumor for a patient, who has cancer in his brain. If he only gets X-CT or MRI pictures, the doctor does not know the size, shape location of the tumor and the relation between the tumor and other organs. This paper presents the formation of stereo images of cancer. On the basis of color code and color 3D reconstruction. The stereo images of tumor, brain and encephalic truncus are formed. The stereo image of cancer can be round on X, Y, Z-coordinates to show the shape from different directions. In order to show the location of tumor, stereo image of tumor and encephalic truncus are provided on different angles. The cross section pictures are also offered to indicate the relation of brain, tumor and encephalic truncus on cross sections. In this paper the calculating of areas, volume and the space between cancer and the side of the brain are also described.

High-resolution digital brain atlases: a Hubble telescope for the brain.

PubMed

Jones, Edward G; Stone, James M; Karten, Harvey J

2011-05-01

We describe implementation of a method for digitizing at microscopic resolution brain tissue sections containing normal and experimental data and for making the content readily accessible online. Web-accessible brain atlases and virtual microscopes for online examination can be developed using existing computer and internet technologies. Resulting databases, made up of hierarchically organized, multiresolution images, enable rapid, seamless navigation through the vast image datasets generated by high-resolution scanning. Tools for visualization and annotation of virtual microscope slides enable remote and universal data sharing. Interactive visualization of a complete series of brain sections digitized at subneuronal levels of resolution offers fine grain and large-scale localization and quantification of many aspects of neural organization and structure. The method is straightforward and replicable; it can increase accessibility and facilitate sharing of neuroanatomical data. It provides an opportunity for capturing and preserving irreplaceable, archival neurohistological collections and making them available to all scientists in perpetuity, if resources could be obtained from hitherto uninterested agencies of scientific support. © 2011 New York Academy of Sciences.

Structural study of Purkinje cell axonal torpedoes in essential tremor.

PubMed

Louis, Elan D; Yi, Hong; Erickson-Davis, Cordelia; Vonsattel, Jean-Paul G; Faust, Phyllis L

2009-02-06

Essential tremor (ET) is one of the most common neurological diseases. A basic understanding of its neuropathology is now emerging. Aside from Purkinje cell loss, a prominent finding is an abundance of torpedoes (rounded swellings of Purkinje cell axons). Such swellings often result from the mis-accumulation of cell constituents. Identifying the basic nature of these accumulations is an important step in understanding the underlying disease process. Torpedoes, only recently identified in ET, have not yet been characterized ultrastructurally. Light and electron microscopy were used to characterize the structural constituents of torpedoes in ET. Formalin-fixed cerebellar cortical tissue from four prospectively collected ET brains was sectioned and immunostained with a monoclonal phosphorylated neurofilament antibody (SMI-31, Covance, Emeryville, CA). Using additional sections from three ET brains, torpedoes were assessed using electron microscopy. Immunoreactivity for phosphorylated neurofilament protein revealed clear labeling of torpedoes in each case. Torpedoes were strongly immunoreactive; in many instances, two or more torpedoes were noted in close proximity to one another. On electron microscopy, torpedoes were packed with randomly arranged 10-12nm neurofilaments. Mitochondria and smooth endoplasmic reticulum were abundant as well, particularly at the periphery of the torpedo. We demonstrated that the torpedoes in ET represent the mis-accumulation of disorganized neurofilaments and other organelles. It is not known where in the pathogenic cascade these accumulations occur (i.e., whether these accumulations are the primary event or a secondary/downstream event) and this deserves further study.

Is performance on the Wechsler test of adult reading affected by traumatic brain injury?

PubMed

Mathias, J L; Bowden, S C; Bigler, E D; Rosenfeld, J V

2007-11-01

The validity of the National Adult Reading Test (NART) as a predictor of premorbid IQ when used with patients who have sustained a traumatic brain injury (TBI) has been questioned in recent years. This study examined whether performance on the Wechsler Test of Adult Reading (WTAR) is similarly affected by TBI in the first year after an injury. The WTAR scores of participants who had sustained a mild TBI (N=82), moderate TBI (N=73), severe TBI (N=61) or an orthopaedic injury (N=95) were compared (cross-sectional study). A subset of 21 mild TBI, 31 moderate TBI, 26 severe TBI and 21 control group participants were additionally reassessed 6 months later to assess the impact of recovery on WTAR scores (longitudinal study). The severe TBI group had significantly lower scores on the WTAR than the mild TBI, moderate TBI and control groups in the cross-sectional study, despite being matched demographically. The findings from the longitudinal study revealed a significant group difference and a small improvement in performance over time but the interaction between group and time was not significant, suggesting that the improvements in WTAR performance over time were not restricted to more severely injured individuals whose performance was temporarily suppressed. These findings suggest that reading performance may be affected by severe TBI and that the WTAR may underestimate premorbid IQ when used in this context, which may cause clinicians to underestimate the cognitive deficits experienced by these patients.

Neurochemistry of olivocochlear neurons in the hamster.

PubMed

Reuss, Stefan; Disque-Kaiser, Ursula; Antoniou-Lipfert, Patricia; Gholi, Maryam Najaf; Riemann, Elke; Riemann, Randolf

2009-04-01

The present study was conducted to characterize the superior olivary complex (SOC) of the lower brain stem in the pigmented Djungarian hamster Phodopus sungorus. Using Nissl-stained serial cryostat sections from fresh-frozen brains, we determined the borders of the SOC nuclei. We also identified olivocochlear (OC) neurons by retrograde neuronal tracing upon injection of Fluoro-Gold into the scala tympani. To evaluate the SOC as a putative source of neuronal nitric oxide synthase (nNOS), arginine-vasopressin (AVP), oxytocin (OT), vasoactive intestinal polypeptide (VIP), or pituitary adenylate cyclase-activating polypeptide (PACAP) that were all found in the cochlea, we conducted immunohistochemistry on sections exhibiting retrogradely labeled neurons. We did not observe AVP-, OT-, or VIP-immunoreactivity, neither in OC neurons nor in the SOC at all, revealing that cochlear AVP, OT, and VIP are of nonolivary origin. However, we found nNOS, the enzyme responsible for nitric oxide synthesis in neurons, and PACAP in neuronal perikarya of the SOC. Retrogradely labeled neurons of the lateral olivocochlear (LOC) system in the lateral superior olive did not contain PACAP and were only infrequently nNOS-immunoreactive. In contrast, some shell neurons and some of the medial OC (MOC) system exhibited immunofluorescence for either substance. Our data obtained from the dwarf hamster Phodopus sungorus confirm previous observations that a part of the LOC system is nitrergic. They further demonstrate that the medial olivocochlear system is partly nitrergic and use PACAP as neurotransmitter or modulator.

An in vivo model of functional and vascularized human brain organoids.

PubMed

Mansour, Abed AlFatah; Gonçalves, J Tiago; Bloyd, Cooper W; Li, Hao; Fernandes, Sarah; Quang, Daphne; Johnston, Stephen; Parylak, Sarah L; Jin, Xin; Gage, Fred H

2018-06-01

Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

Human-specific features of spatial gene expression and regulation in eight brain regions.

PubMed

Xu, Chuan; Li, Qian; Efimova, Olga; He, Liu; Tatsumoto, Shoji; Stepanova, Vita; Oishi, Takao; Udono, Toshifumi; Yamaguchi, Katsushi; Shigenobu, Shuji; Kakita, Akiyoshi; Nawa, Hiroyuki; Khaitovich, Philipp; Go, Yasuhiro

2018-06-13

Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1,851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, while the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species. Published by Cold Spring Harbor Laboratory Press.

Alterations in brain cerebral cortex proteome of rabies-infected cat.

PubMed

Kasempimolporn, Songsri; Lumlertdacha, Boonlert; Chulasugandha, Pannipa; Boonchang, Supatsorn; Sitprija, Visith

2014-07-01

Comparative proteome analysis using brain cerebral cortex tissues from cats and dogs infected with/without rabies virus were conducted using both two-dimensional gel-electrophoresis (2-DE) and 2-D fluorescence difference gel- electrophoresis (2D-DIGE) methods. The 2-DE gel images of all samples revealed >1,000 protein spots in each gel. Quantitative intensity analysis revealed the same overall protein pattern in certain regions of the gel, but the rabies-infected brains exhibited more protein spots than the non-infected controls. From approximately 880 protein spots detected by 2D-DIGE, 65 protein spots were increased and 46 were decreased. Eight of these protein spots were randomly selected and annotated by reference to previous known proteome data of rabid dog brains. They were similarly altered in both of the rabies-infected cats and dogs. A more detailed comparison of changes in proteomic profiles of brains between rabid cats and dogs should shed some light on the pathophysiological mechanism of rabies in domestic animals, as most rabies cases have been traceable to or believed to have originated from rabid dogs.

The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.

PubMed

Zelikowsky, Moriel; Hui, May; Karigo, Tomomi; Choe, Andrea; Yang, Bin; Blanco, Mario R; Beadle, Keith; Gradinaru, Viviana; Deverman, Benjamin E; Anderson, David J

2018-05-17

Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses. Multiplexed analysis of Tac2/NkB function in multiple brain areas revealed dissociable, region-specific requirements for both the peptide and its receptor in different SIS-induced behavioral changes. Thus, Tac2 coordinates a pleiotropic brain state caused by SIS via a distributed mode of action. These data reveal the profound effects of prolonged social isolation on brain chemistry and function and suggest potential new therapeutic applications for Nk3R antagonists. Copyright © 2018 Elsevier Inc. All rights reserved.

In situ hybridization and immunofluorescence on resin-embedded tissue to identify the components of Nissl substance.

PubMed

Singhrao, Sim K; Nair-Roberts, Radha G

2010-05-01

It is not clear whether the Nissl substance is present at the axon hillock. To clarify this gap in knowledge, we conducted in situ hybridization (ISH) on mouse brain tissue using 30-microm cryostat and 1-3-microm acrylic resin sections. Cryostat and rehydrated resin sections were exposed to digoxygenin-labeled glutamic acid decarboxylase 1 sense and antisense riboprobes. Consecutive sections from tissue embedded in resin were subjected to the ribosomal protein L26 primary antibody to determine the distribution of the ribo/polysomes. ISH results from the antisense riboprobe in both cryostat and resin-embedded tissue sections demonstrated an abundance of message in the neurons from the substantia nigra pars reticulate. In addition, the resin sections demonstrated hybridization signal in the axon hillock of some neurons. Immunofluorescence labeling of consecutive sections using an antibody to the most abundant ribosomal protein L26 confirmed their distribution in the cell body and the axon hillock of similar neurons. Compared with the 30-microm cryostat sections, the most striking feature of ISH in the thinner resin (2-3 microm) sections was that there was a phenomenal improvement in the overall clarity and spatial resolution. Reexamination of the axon hillock when continuous with the cell body in cryostat sections revealed that the same message was also present, except it was overlooked initially because of overlapping cell populations in thick tissue slices. As ribosomes are a component of Nissl substance, we propose that the axon hillock, like other parts of the neuron, does contain Nissl substance. (c) 2009 Wiley-Liss, Inc.

Brain CT image similarity retrieval method based on uncertain location graph.

PubMed

Pan, Haiwei; Li, Pengyuan; Li, Qing; Han, Qilong; Feng, Xiaoning; Gao, Linlin

2014-03-01

A number of brain computed tomography (CT) images stored in hospitals that contain valuable information should be shared to support computer-aided diagnosis systems. Finding the similar brain CT images from the brain CT image database can effectively help doctors diagnose based on the earlier cases. However, the similarity retrieval for brain CT images requires much higher accuracy than the general images. In this paper, a new model of uncertain location graph (ULG) is presented for brain CT image modeling and similarity retrieval. According to the characteristics of brain CT image, we propose a novel method to model brain CT image to ULG based on brain CT image texture. Then, a scheme for ULG similarity retrieval is introduced. Furthermore, an effective index structure is applied to reduce the searching time. Experimental results reveal that our method functions well on brain CT images similarity retrieval with higher accuracy and efficiency.

Penetration of immunoreagents in Vibratome-sectioned brain: a light and electron microscopic study.

PubMed

Piekut, D T; Casey, S M

1983-05-01

Immunocytochemical studies on the localization of peptides at the ultrastructural level have most frequently involved the application of the peroxidase--antiperoxidase (PAP) method of immunocytochemistry and the use of the preembedding or postembedding staining procedures. The present study was designed to determine the depth of penetration of Vibratome tissue sections by immunoreagents used in the preembedding method in which immunostaining of unembedded fixed tissue sections is accomplished prior to tissue dehydration and embedment. Our data indicate that penetration of immunoreagents is restricted to the superficial 8-9 micrometers of a 80-micrometers thick Vibratome tissue section of hypothalamus of brain using antisera generated against arginine vasopressin. The final immunoreaction product visualized in a Vibratome tissue section may reflect only a fraction of the amount of hormone contained within the thickness of the tissue section.

Social Workers' Perceived Role Clarity as Members of an Interdisciplinary Team in Brain Injury Settings.

PubMed

Vungkhanching, Martha; Tonsing, Kareen N

2016-08-11

This study investigated social workers' role clarity as members of an interdisciplinary team in traumatic and acquired brain injury treatment settings. A total of 37 social workers from 7 Western countries completed an anonymous online survey questionnaire. The majority of participants have more than 10 years of experience working in brain injury treatment settings (59.5%), and about 54% have been in their current employment for more than 10 years. Findings revealed that there were significant positive correlations between perceived respect, team collaboration, and perceived value of self for team with role clarity. Multiple regression analysis revealed that perceived value of self for team was a significant predictor of role clarity (p < .05).

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed

Ng, S C; Lee, M K; Teh, A

1989-11-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome.

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed Central

Ng, S. C.; Lee, M. K.; Teh, A.

1989-01-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome. PMID:2616421

The Theory of Localist Representation and of a Purely Abstract Cognitive System: The Evidence from Cortical Columns, Category Cells, and Multisensory Neurons.

PubMed

Roy, Asim

2017-01-01

The debate about representation in the brain and the nature of the cognitive system has been going on for decades now. This paper examines the neurophysiological evidence, primarily from single cell recordings, to get a better perspective on both the issues. After an initial review of some basic concepts, the paper reviews the data from single cell recordings - in cortical columns and of category-selective and multisensory neurons. In neuroscience, columns in the neocortex (cortical columns) are understood to be a basic functional/computational unit. The paper reviews the fundamental discoveries about the columnar organization and finds that it reveals a massively parallel search mechanism. This columnar organization could be the most extensive neurophysiological evidence for the widespread use of localist representation in the brain. The paper also reviews studies of category-selective cells. The evidence for category-selective cells reveals that localist representation is also used to encode complex abstract concepts at the highest levels of processing in the brain. A third major issue is the nature of the cognitive system in the brain and whether there is a form that is purely abstract and encoded by single cells. To provide evidence for a single-cell based purely abstract cognitive system, the paper reviews some of the findings related to multisensory cells. It appears that there is widespread usage of multisensory cells in the brain in the same areas where sensory processing takes place. Plus there is evidence for abstract modality invariant cells at higher levels of cortical processing. Overall, that reveals the existence of a purely abstract cognitive system in the brain. The paper also argues that since there is no evidence for dense distributed representation and since sparse representation is actually used to encode memories, there is actually no evidence for distributed representation in the brain. Overall, it appears that, at an abstract level, the brain is a massively parallel, distributed computing system that is symbolic. The paper also explains how grounded cognition and other theories of the brain are fully compatible with localist representation and a purely abstract cognitive system.

The Theory of Localist Representation and of a Purely Abstract Cognitive System: The Evidence from Cortical Columns, Category Cells, and Multisensory Neurons

PubMed Central

Roy, Asim

2017-01-01

The debate about representation in the brain and the nature of the cognitive system has been going on for decades now. This paper examines the neurophysiological evidence, primarily from single cell recordings, to get a better perspective on both the issues. After an initial review of some basic concepts, the paper reviews the data from single cell recordings – in cortical columns and of category-selective and multisensory neurons. In neuroscience, columns in the neocortex (cortical columns) are understood to be a basic functional/computational unit. The paper reviews the fundamental discoveries about the columnar organization and finds that it reveals a massively parallel search mechanism. This columnar organization could be the most extensive neurophysiological evidence for the widespread use of localist representation in the brain. The paper also reviews studies of category-selective cells. The evidence for category-selective cells reveals that localist representation is also used to encode complex abstract concepts at the highest levels of processing in the brain. A third major issue is the nature of the cognitive system in the brain and whether there is a form that is purely abstract and encoded by single cells. To provide evidence for a single-cell based purely abstract cognitive system, the paper reviews some of the findings related to multisensory cells. It appears that there is widespread usage of multisensory cells in the brain in the same areas where sensory processing takes place. Plus there is evidence for abstract modality invariant cells at higher levels of cortical processing. Overall, that reveals the existence of a purely abstract cognitive system in the brain. The paper also argues that since there is no evidence for dense distributed representation and since sparse representation is actually used to encode memories, there is actually no evidence for distributed representation in the brain. Overall, it appears that, at an abstract level, the brain is a massively parallel, distributed computing system that is symbolic. The paper also explains how grounded cognition and other theories of the brain are fully compatible with localist representation and a purely abstract cognitive system. PMID:28261127

Live imaging of the innate immune response in neonates reveals differential TLR2 dependent activation patterns in sterile inflammation and infection.

PubMed

Lalancette-Hébert, Melanie; Faustino, Joel; Thammisetty, Sai Sampath; Chip, Sophorn; Vexler, Zinaida S; Kriz, Jasna

2017-10-01

Activation of microglial cells in response to brain injury and/or immune stimuli is associated with a marked induction of Toll-like receptors (TLRs). While in adult brain, the contribution of individual TLRs, including TLR2, in pathophysiological cascades has been well established, their role and spatial and temporal induction patterns in immature brain are far less understood. To examine whether infectious stimuli and sterile inflammatory stimuli trigger distinct TLR2-mediated innate immune responses, we used three models in postnatal day 9 (P9) mice, a model of infection induced by systemic endotoxin injection and two models of sterile inflammation, intra-cortical IL-1β injection and transient middle cerebral artery occlusion (tMCAO). We took advantage of a transgenic mouse model bearing the dual reporter system luciferase/GFP under transcriptional control of a murine TLR2 promoter (TLR2-luc-GFP) to visualize the TLR2 response in the living neonatal brain and then determined neuroinflammation, microglial activation and leukocyte infiltration. We show that in physiological postnatal brain development the in vivo TLR2-luc signal undergoes a marked ∼30-fold decline and temporal-spatial changes during the second and third postnatal weeks. We then show that while endotoxin robustly induces the in vivo TLR2-luc signal in the living brain and increases levels of several inflammatory cytokines and chemokines, the in vivo TLR2-luc signal is reduced after both IL-1β and tMCAO and the inflammatory response is muted. Immunofluorescence revealed that microglial cells are the predominant source of TLR2 production during postnatal brain development and in all three neonatal models studied. Flow cytometry revealed developmental changes in CD11b + /CD45 + and CD11b + /Ly6C + cell populations, involvement of cells of the monocyte lineage, but lack of Ly6G + neutrophils or CD3 + cells in acutely injured neonatal brains. Cumulatively, our results suggest distinct TLR2 induction patterns following PAMP and DAMP - mediated inflammation in immature brain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Vision's Brain.

ERIC Educational Resources Information Center

Miller, Julie Ann

1978-01-01

The functional architecture of the primary visual cortex has been explored by monitoring the responses of individual brain cells to visual stimuli. A combination of anatomical and physiological techniques reveals groups of functionally related cells, juxtaposed and superimposed, in a sometimes complex, but presumably efficient, structure. (BB)

Magnetic resonance imaging of the pediatric brain

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

Salamon, G.; Raynaud, C.; Regis, J.

1990-01-01

The atlas presents sequences of MRI sections parallel to the orbito-meatal plane in children from birth through the age of sixteen years. Each child was studied horizontally and sagitally and three-dimensional brain images were reconstructed to facilitate accurate identification of sulci and gyri. The images show crucial aspects of brain development such as the constancy of the brain stem and primitive brain from birth onward; the development of the telencephalon, characterized by deepening of sulci and growth of the cerebral cortex surface; and the different stages of white matter myelinization.

[Regularities of fixation of brain serum antibodies from patients with lateral amyotrophic sclerosis in rabbit CNS].

PubMed

Musaeva, L S; Gannyshkina, I V; Zavalishin, I A; Markova, E D; Ivanova-Smolenskaia, I A

2002-01-01

Kuhns' indirect immunofluorescent test was used to study fixation of serum brain antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is characterized by formation of brain Ab complementary to various structures of nervous and glial cells, myelin of fibers from different conducting systems, vessels which exhibit both common and individual antigenic properties. It was found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar, cervicothoracic and lumbosacral LAS in different CNS structures varies.

Cocaine, Appetitive Memory and Neural Connectivity

PubMed Central

Ray, Suchismita

2013-01-01

This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested. PMID:25009766

Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain.

PubMed

Canis, Martin; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

2009-02-27

The brain is capable of taking up monocarboxylates as energy substrates. Under physiological conditions, plasma levels of monocarboxylates are very low and glucose is the primary energy substrate in brain metabolism. However, given conditions such as hyperglycemia and ketosis, levels of circulating monocarboxylates such as lactate and pyruvate are elevated. Previous studies reported an increased expression of monocarboxylate transporter MCT1 in brain following ketotic diet. The major aim of the present study was to answer the question whether chronic hyperglycemia is likewise sufficient to change local densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby enters the brain parenchyma via glucose transporters and is partially metabolised by astrocytes, which then release lactate to meet the energetic demands of surrounding neurons. Streptozotocin was given intravenously to induce chronic hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. The density of monocarboxylate transporter MCT1 was significantly increased in 10 of 24 brain structures investigated (median increase 11.7+/-3.4 %). Immunocytochemical stainings of these substructures revealed an expression of MCT1 within endothelial cells and astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study under normo- and hyperglycemic conditions revealed a partial correlation between both parameters and under both conditions. Four out of 10 brain areas, which showed a significant increase in MCT1 density due to hyperglycemia, also showed a significant increase in LCGU. In summary, our data show that chronic hyperglycemia induces a moderate increase of local and global density of MCT1 in several brain structures. However, in terms of brain topologies and substructures this phenomenon did only partially match with increased LCGU. It is concluded that MCT1 transporters were up-regulated during chronic hyperglycemia at the level of brain substructures and independently of LCGU.

Structural analysis of the tongue and hyoid apparatus in a woodpecker

PubMed Central

Jung, Jae-Young; Naleway, Steven E.; Yaraghi, Nicholas A.; Herrera, Steven; Sherman, Vincent R.; Bushong, Eric A.; Ellisman, Mark H.; Kisailus, David; McKittrick, Joanna

2016-01-01

Woodpeckers avoid brain injury while they peck at trees up to 20 Hz with speeds up to 7 m/s, undergoing decelerations up to 1200 g. Along with the head, beak and neck, the hyoid apparatus (tongue bone and associated soft tissues) is subjected to these high impact forces. The shape of the hyoid apparatus is unusual in woodpeckers and its structure and mechanical properties have not been reported in detail. High-resolution X-ray micro-computed tomography and scanning electron microscopy with energy dispersive X-ray spectroscopy were performed and correlated with nanoindentation mapping. The hyoid apparatus has four distinct bone sections, with three joints between these sections. Nanoindentation results on cross-sectional regions of each bone reveal a previously unreported structure consisting of a stiff core and outer, more compliant shell with moduli of up to 27.4 GPa and 8.5 GPa, respectively. The bending resistance is low at the posterior section of the hyoid bones, indicating that this region has a high degree of flexibility to absorb impact. These new structural findings can be applied to further studies on the energy dissipation of the woodpecker during its drumming behavior, and may have implications for the design of engineered impact-absorbing structures. PMID:27000554

Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury.

PubMed

Dennis, Emily L; Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C; Thompson, Paul M; Asarnow, Robert F

2016-05-01

Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1-6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI.

Differences in Brain Adaptive Functional Reorganization in Right and Left Total Brachial Plexus Injury Patients.

PubMed

Feng, Jun-Tao; Liu, Han-Qiu; Xu, Jian-Guang; Gu, Yu-Dong; Shen, Yun-Dong

2015-09-01

Total brachial plexus avulsion injury (BPAI) results in the total functional loss of the affected limb and induces extensive brain functional reorganization. However, because the dominant hand is responsible for more cognitive-related tasks, injuries on this side induce more adaptive changes in brain function. In this article, we explored the differences in brain functional reorganization after injuries in unilateral BPAI patients. We applied resting-state functional magnetic resonance imaging scanning to 10 left and 10 right BPAI patients and 20 healthy control subjects. The amplitude of low-frequency fluctuation (ALFF), which is a resting-state index, was calculated for all patients as an indication of the functional activity level of the brain. Two-sample t-tests were performed between left BPAI patients and controls, right BPAI patients and controls, and between left and right BPAI patients. Two-sample t-tests of the ALFF values revealed that right BPAIs induced larger scale brain reorganization than did left BPAIs. Both left and right BPAIs elicited a decreased ALFF value in the right precuneus (P < 0.05, Alphasim corrected). In addition, right BPAI patients exhibited increased ALFF values in a greater number of brain regions than left BPAI patients, including the inferior temporal gyrus, lingual gyrus, calcarine sulcus, and fusiform gyrus. Our results revealed that right BPAIs induced greater extents of brain functional reorganization than left BPAIs, which reflected the relatively more extensive adaptive process that followed injuries of the dominant hand. Copyright © 2015 Elsevier Inc. All rights reserved.

Revealing topological organization of human brain functional networks with resting-state functional near infrared spectroscopy.

PubMed

Niu, Haijing; Wang, Jinhui; Zhao, Tengda; Shu, Ni; He, Yong

2012-01-01

The human brain is a highly complex system that can be represented as a structurally interconnected and functionally synchronized network, which assures both the segregation and integration of information processing. Recent studies have demonstrated that a variety of neuroimaging and neurophysiological techniques such as functional magnetic resonance imaging (MRI), diffusion MRI and electroencephalography/magnetoencephalography can be employed to explore the topological organization of human brain networks. However, little is known about whether functional near infrared spectroscopy (fNIRS), a relatively new optical imaging technology, can be used to map functional connectome of the human brain and reveal meaningful and reproducible topological characteristics. We utilized resting-state fNIRS (R-fNIRS) to investigate the topological organization of human brain functional networks in 15 healthy adults. Brain networks were constructed by thresholding the temporal correlation matrices of 46 channels and analyzed using graph-theory approaches. We found that the functional brain network derived from R-fNIRS data had efficient small-world properties, significant hierarchical modular structure and highly connected hubs. These results were highly reproducible both across participants and over time and were consistent with previous findings based on other functional imaging techniques. Our results confirmed the feasibility and validity of using graph-theory approaches in conjunction with optical imaging techniques to explore the topological organization of human brain networks. These results may expand a methodological framework for utilizing fNIRS to study functional network changes that occur in association with development, aging and neurological and psychiatric disorders.

Metabolic connectomics targeting brain pathology in dementia with Lewy bodies

PubMed Central

Caminiti, Silvia P; Tettamanti, Marco; Sala, Arianna; Presotto, Luca; Iannaccone, Sandro; Cappa, Stefano F; Magnani, Giuseppe

2016-01-01

Dementia with Lewy bodies is characterized by α-synuclein accumulation and degeneration of dopaminergic and cholinergic pathways. To gain an overview of brain systems affected by neurodegeneration, we characterized the [18F]FDG-PET metabolic connectivity in 42 dementia with Lewy bodies patients, as compared to 42 healthy controls, using sparse inverse covariance estimation method and graph theory. We performed whole-brain and anatomically driven analyses, targeting cholinergic and dopaminergic pathways, and the α-synuclein spreading. The first revealed substantial alterations in connectivity indexes, brain modularity, and hubs configuration. Namely, decreases in local metabolic connectivity within occipital cortex, thalamus, and cerebellum, and increases within frontal, temporal, parietal, and basal ganglia regions. There were also long-range disconnections among these brain regions, all supporting a disruption of the functional hierarchy characterizing the normal brain. The anatomically driven analysis revealed alterations within brain structures early affected by α-synuclein pathology, supporting Braak’s early pathological staging in dementia with Lewy bodies. The dopaminergic striato-cortical pathway was severely affected, as well as the cholinergic networks, with an extensive decrease in connectivity in Ch1-Ch2, Ch5-Ch6 networks, and the lateral Ch4 capsular network significantly towards the occipital cortex. These altered patterns of metabolic connectivity unveil a new in vivo scenario for dementia with Lewy bodies underlying pathology in terms of changes in whole-brain metabolic connectivity, spreading of α-synuclein, and neurotransmission impairment. PMID:27306756

Gaining Insight of Fetal Brain Development with Diffusion MRI and Histology

PubMed Central

Huang, Hao; Vasung, Lana

2013-01-01

Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic level. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. PMID:23796901

From Hippocampus to Whole-Brain: The Role of Integrative Processing in Episodic Memory Retrieval

PubMed Central

Geib, Benjamin R.; Stanley, Matthew L.; Dennis, Nancy A.; Woldorff, Marty G.; Cabeza, Roberto

2017-01-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. PMID:28112460

Gene expression changes in the course of normal brain aging are sexually dimorphic

PubMed Central

Berchtold, Nicole C.; Cribbs, David H.; Coleman, Paul D.; Rogers, Joseph; Head, Elizabeth; Kim, Ronald; Beach, Tom; Miller, Carol; Troncoso, Juan; Trojanowski, John Q.; Zielke, H. Ronald; Cotman, Carl W.

2008-01-01

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20–99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea. PMID:18832152

A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads.

PubMed

Braak, E; Braak, H; Mandelkow, E M

1994-01-01

Frontal sections of the temporal lobe including the transentorhinal/entorhinal region, amygdala, and/or hippocampus from human adult brains are studied for cytoskeleton changes using immunostaining with the antibodies AT8 and Alz-50 and selective silver impregnation methods for neurofibrillary changes of the Alzheimer type. For the purpose of correlation, the two methods are carried out one after the other on the same section. Layer pre-alpha in the transentorhinal/entorhinal region harbours nerve cells which are among the first nerve cells in the entire brain to show the development of neurofibrillary changes. This presents the opportunity for study of both early events in the destruction of the cytoskeleton in individual neurons, and to relate changes which occur in the neuronal processes in the absence of alterations in their immediate surroundings to those happening in the soma. Immunoreactions with the AT8 antibody in particular reveal a clear sequence of changes in the neuronal cytoskeleton. Group 1 neurons present initial cytoskeleton changes in that the soma, dendrites, and axon are completely marked by granular AT8 immunoreactive material. These neurons appear quite normal and turn out to be devoid of argyrophilic material when observed in silver-stained sections. Group 2 neurons show changes in the cellular processes. The terminal tuft of the apical dendrite is replaced by tortuous varicose fibres and coarse granules. The distal portions of the dendrites are curved and show appendages and thickened portions. Intensely homogeneously immunostained rod-like inclusions are encountered in these thickened portions and in the soma. A number of these rod-like inclusions are visible after silver staining, as well. Group 3 neurons display even more pronounced alterations of their distal--most dendritic portions. The intermediate dendritic parts lose immunoreactivity, but the soma is homogeneously immunostained. Silver staining reveals in most of the distal dendritic parts neuropil threads, and in the soma a classic neurofibrillary tangle. Group 4 structures are marked by accumulations of coarse AT8-immunoreactive granules. Silver staining provides evidence that the fibrillary material has become an extraneuronal, "early" ghost tangle. Finally, group 5 structures present "late" ghost tangles in silver-stained sections but fail to demonstrate AT8 immunoreactivity. It is suggested that the altered tau protein shown by the antibody AT8 represents an early cytoskeleton change which eventually leads to the formation of argyrophilic neurofibrillary tangles and neuropil threads.

From hippocampus to whole-brain: The role of integrative processing in episodic memory retrieval.

PubMed

Geib, Benjamin R; Stanley, Matthew L; Dennis, Nancy A; Woldorff, Marty G; Cabeza, Roberto

2017-04-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242-2259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

PubMed

Aidoud, Nacima; Delplanque, Bernadette; Baudry, Charlotte; Garcia, Cyrielle; Moyon, Anais; Balasse, Laure; Guillet, Benjamin; Antona, Claudine; Darmaun, Dominique; Fraser, Karl; Ndiaye, Sega; Leruyet, Pascale; Martin, Jean-Charles

2018-03-22

We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

Employment status and termination among survivors of pediatric brain tumors: a cross-sectional survey.

PubMed

Sato, Iori; Higuchi, Akiko; Yanagisawa, Takaaki; Murayama, Shiho; Kumabe, Toshihiro; Sugiyama, Kazuhiko; Mukasa, Akitake; Saito, Nobuhito; Sawamura, Yutaka; Terasaki, Mizuhiko; Shibui, Soichiro; Takahashi, Jun; Nishikawa, Ryo; Ishida, Yasushi; Kamibeppu, Kiyoko

2018-04-30

Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors' employment status. A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants' first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses. Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence). Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

PubMed Central

Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

2014-01-01

Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

Cross-population myelination covariance of human cerebral cortex.

PubMed

Ma, Zhiwei; Zhang, Nanyin

2017-09-01

Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions. Using myelin content MRI maps from the Human Connectome Project, here we showed that the cortical myelination covariance was highly reproducible, and exhibited a brain organization similar to that previously revealed by other connectivity measures. Additionally, the myelination covariance network shared common topological features of human brain networks such as small-worldness. Furthermore, we found that the correlation between myelination covariance and resting-state functional connectivity (RSFC) was uniform within each resting-state network (RSN), but could considerably vary across RSNs. Interestingly, this myelination covariance-RSFC correlation was appreciably stronger in sensory and motor networks than cognitive and polymodal association networks, possibly due to their different circuitry structures. This study has established a new brain connectivity measure specifically related to axons, and this measure can be valuable to investigating coordinated myeloarchitecture development. Hum Brain Mapp 38:4730-4743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Brain growth rate abnormalities visualized in adolescents with autism.

PubMed

Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

2013-02-01

Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain

NASA Technical Reports Server (NTRS)

Murashov, A. K.; Wolgemuth, D. J.

1996-01-01

We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

[Value of computer tomography in the managment of brain injuries].

PubMed

Keita, A D; Toure, M; Sissako, A; Doumbia, S; Coulibaly, Y; Doumbia, D; Kane, M; Diallo, A K; Toure, A A; Traore, I

2005-11-01

The purpose of this prospective study conducted from January 2001 to December 2001 was to ascertain the value of computer tomography for evaluation of brain injuries. Computer tomography was performed using a Toshiba X VID system with contiguous 5 mm axial sections through the posterior fossa and 10 mm contiguous axial sections through the subtentorial region without contrast injection. A total of 107 patients with brain injuries were enrolled over the one-year study period. These patients accounted for 0.8% of all admissions to surgical emergency unit of Gabriel Toure Hospital in Bamako, Mali. The predominant age group for brain injuries was the 20- to 29-year-old group (35 cases). The male-to-female sex ratio was 5:1. Vehicular accident was the most frequent cause of brain injury (76 cases). Trauma was severe in 48 patients with a Glasgow score less than 8. Coma occurred immediately after injury in 90 cases. Ventricular hemorrhage led to coma in 100% of cases whereas brain hemorrhage and hematoma led to coma in 93.3% and 83.3% of cases respectively. Treatment was medical in 99 cases and neurosurgical in 8. The mortality rate was 34% and the morbidity rate (permanent sequels) was 36%. Computer tomography is a valuable tool for therapeutic decision-making in medico-surgical emergencies involving brain injuries.

Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI Study of Normal Brain Development.

PubMed

2012-01-01

Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

Autoradiographic evidence for two classes of mu opioid binding sites in rat brain using (/sup 125/I)FK33824

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

Rothman, R.B.; Jacobson, A.E.; Rice, K.C.

1987-11-01

Previous studies demonstrated that pretreatment of brain membranes with the irreversible mu antagonist, beta-funaltrexamine (beta-FNA), partially eliminated mu binding sites (25,35), consistent with the existence of two mu binding sites distinguished by beta-FNA. This paper tests the hypothesis that the FNA-sensitive and FNA-insensitive mu binding sites have different anatomical distributions in rat brain. Prior to autoradiographic visualization of mu binding sites, (/sup 3/H)oxymorphone, (/sup 3/H)D-ala2-MePhe4, Gly-ol5-enkephalin (DAGO), and (/sup 125/I)D-ala2-Me-Phe4-met(o)-ol)enkephalin (FK33824) were shown to selectively label mu binding sites using slide mounted sections of molded minced rat brain. As found using membranes, beta-FNA eliminated only a portion of mu bindingmore » sites. Autoradiographic visualization of mu binding sites using the mu-selective ligand (/sup 125/I)FK33824 in control and FNA-treated sections of rat brain demonstrated that the proportion of mu binding sites sensitive to beta-FNA varied across regions of the brain, particularly the dorsal thalamus, ventrobasal complex and the hypothalamus, providing anatomical data supporting the existence of two classes of mu binding sites in rat brain.« less

Bringing the Brain into Assessment.

ERIC Educational Resources Information Center

Caine, Geoffrey; Caine, Renate Nummela

1999-01-01

Brain research explains why testing for surface knowledge (memorization) reveals relatively little about real, usable knowledge. Assessment must contribute to real-world experience, relate to real-world performance, can never be fully translated into representative symbols or numbers, and can induce both helplessness (interference with meaningful…

Pcdh19 Loss-of-Function Increases Neuronal Migration In Vitro but is Dispensable for Brain Development in Mice

PubMed Central

Pederick, Daniel T.; Homan, Claire C.; Jaehne, Emily J.; Piltz, Sandra G.; Haines, Bryan P.; Baune, Bernhard T.; Jolly, Lachlan A.; Hughes, James N.; Gecz, Jozef; Thomas, Paul Q.

2016-01-01

Protocadherin 19 (Pcdh19) is an X-linked gene belonging to the protocadherin superfamily, whose members are predominantly expressed in the central nervous system and have been implicated in cell-cell adhesion, axon guidance and dendrite self-avoidance. Heterozygous loss-of-function mutations in humans result in the childhood epilepsy disorder PCDH19 Girls Clustering Epilepsy (PCDH19 GCE) indicating that PCDH19 is required for brain development. However, understanding PCDH19 function in vivo has proven challenging and has not been studied in mammalian models. Here, we validate a murine Pcdh19 null allele in which a β-Geo reporter cassette is expressed under the control of the endogenous promoter. Analysis of β-Geo reporter activity revealed widespread but restricted expression of PCDH19 in embryonic, postnatal and adult brains. No gross morphological defects were identified in Pcdh19+/β-Geo and Pcdh19Y/β-Geo brains and the location of Pcdh19 null cells was normal. However, in vitro migration assays revealed that the motility of Pcdh19 null neurons was significantly elevated, potentially contributing to pathogenesis in patients with PCDH19 mutations. Overall our initial characterization of Pcdh19+/β-Geo, Pcdh19β-Geo/β-Geo and Pcdh19Y/β-Geomice reveals that despite widespread expression of Pcdh19 in the CNS, and its role in human epilepsy, its function in mice is not essential for brain development. PMID:27240640

MRI-Based Measurement of Brain Stem Cross-Sectional Area in Relapsing-Remitting Multiple Sclerosis.

PubMed

Chivers, Tomos R; Constantinescu, Cris S; Tench, Christopher R

2015-01-01

To determine if patients with relapsing-remitting multiple sclerosis (RRMS) have a reduced brain stem cross-sectional area (CSA) compared to age- and sex-matched controls. The brain stem is a common site of involvement in MS. However, relatively few imaging studies have investigated brain stem atrophy. Brain magnetic resonance imaging (MRI) was performed on patients and controls using a 1.5T MRI scanner with a quadrature head coil. Three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images with 128 contiguous slices, covering the whole brain and brain stem and a T2-weighted image with 3 mm transverse contiguous images were acquired. We measured the brain stem CSA at three sites, the midbrain, the pons, and the medulla oblongata in 35 RRMS patients and 35 controls using a semiautomated algorithm. CSA readings were normalized using the total external cranial volume to reduce normal population variance and increase statistical power. A significant CSA reduction was found in the midbrain (P ≤ .001), pons (P ≤ .001), and the medulla oblongata (P = .047) postnormalization. A CSA reduction of 9.3% was found in the midbrain, 8.7% in the pons, and 6.5% in the medulla oblongata. A significantly reduced, normalized brain stem CSA was detected in all areas of the brain stem of the RRMS patients, when compared to age- and gender-matched controls. Lack of detectable upper cervical cord atrophy in the same patients suggests some independence of the MS pathology in these regions. Copyright © 2015 by the American Society of Neuroimaging.

Tracking the Spatiotemporal Neural Dynamics of Real-world Object Size and Animacy in the Human Brain.

PubMed

Khaligh-Razavi, Seyed-Mahdi; Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2018-06-07

Animacy and real-world size are properties that describe any object and thus bring basic order into our perception of the visual world. Here, we investigated how the human brain processes real-world size and animacy. For this, we applied representational similarity to fMRI and MEG data to yield a view of brain activity with high spatial and temporal resolutions, respectively. Analysis of fMRI data revealed that a distributed and partly overlapping set of cortical regions extending from occipital to ventral and medial temporal cortex represented animacy and real-world size. Within this set, parahippocampal cortex stood out as the region representing animacy and size stronger than most other regions. Further analysis of the detailed representational format revealed differences among regions involved in processing animacy. Analysis of MEG data revealed overlapping temporal dynamics of animacy and real-world size processing starting at around 150 msec and provided the first neuromagnetic signature of real-world object size processing. Finally, to investigate the neural dynamics of size and animacy processing simultaneously in space and time, we combined MEG and fMRI with a novel extension of MEG-fMRI fusion by representational similarity. This analysis revealed partly overlapping and distributed spatiotemporal dynamics, with parahippocampal cortex singled out as a region that represented size and animacy persistently when other regions did not. Furthermore, the analysis highlighted the role of early visual cortex in representing real-world size. A control analysis revealed that the neural dynamics of processing animacy and size were distinct from the neural dynamics of processing low-level visual features. Together, our results provide a detailed spatiotemporal view of animacy and size processing in the human brain.

Mapping Cortical Laminar Structure in the 3D BigBrain.

PubMed

Wagstyl, Konrad; Lepage, Claude; Bludau, Sebastian; Zilles, Karl; Fletcher, Paul C; Amunts, Katrin; Evans, Alan C

2018-07-01

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study.

PubMed

Nabavi, Seyed Saeed; Partovi, Parinaz

2017-01-01

Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term.

Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

DTIC Science & Technology

2012-03-01

blast injury mechanisms in rat TBI - Roles of polyunsaturated fatty acids in traumatic brain injury vulnerabilities and resilience: evaluation of...salutary effects of DHA supplementation using neurolipidomics and functional outcome assessments - Diagnostic and Therapeutic Targeting of...immunohistochemical assessments reveal greater glial fibrillary acidic protein (GFAP) and IBa1 immunoreactivity in rats subjected to combined injuries than are

Self-averaging in complex brain neuron signals

NASA Astrophysics Data System (ADS)

Bershadskii, A.; Dremencov, E.; Fukayama, D.; Yadid, G.

2002-12-01

Nonlinear statistical properties of Ventral Tegmental Area (VTA) of limbic brain are studied in vivo. VTA plays key role in generation of pleasure and in development of psychological drug addiction. It is shown that spiking time-series of the VTA dopaminergic neurons exhibit long-range correlations with self-averaging behavior. This specific VTA phenomenon has no relation to VTA rewarding function. Last result reveals complex role of VTA in limbic brain.

Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and renal arteries.

PubMed

Uchikawa, Hideki; Fujii, Katsunori; Fujita, Mayuko; Okunushi, Tomoko; Shimojo, Naoki

2017-09-01

Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen. Given that this fulfilled diagnostic criteria, we finally diagnosed him as having moyamoya syndrome, though the etiology was unclear. Interestingly, a whole vessel survey revealed vascular stenosis of abdominal aorta and renal arteries, in which the former has not been reported in moyamoya syndrome. We considered that brain calcification was gradually formed by decreased cerebral vascular flow from infancy, and stenosis of abdominal aorta was possibly extended from renal arteries. This is, moyamoya syndrome with brain calcification and stenosis of abdominal aorta, suggesting that morphological screening of whole vessels containing cerebral and abdominal arteries should be considered in cases of slowly progressive brain calcification. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity.

PubMed

Giles, James A; Greenhalgh, Andrew D; Davies, Claire L; Denes, Adam; Shaw, Tovah; Coutts, Graham; Rothwell, Nancy J; McColl, Barry W; Allan, Stuart M

2015-02-01

The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders. © 2014 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.

Connectivity dynamics in typical development and its relationship to autistic traits and autism spectrum disorder.

PubMed

Rashid, Barnaly; Blanken, Laura M E; Muetzel, Ryan L; Miller, Robyn; Damaraju, Eswar; Arbabshirani, Mohammad R; Erhardt, Erik B; Verhulst, Frank C; van der Lugt, Aad; Jaddoe, Vincent W V; Tiemeier, Henning; White, Tonya; Calhoun, Vince

2018-03-30

Recent advances in neuroimaging techniques have provided significant insights into developmental trajectories of human brain function. Characterizations of typical neurodevelopment provide a framework for understanding altered neurodevelopment, including differences in brain function related to developmental disorders and psychopathology. Historically, most functional connectivity studies of typical and atypical development operate under the assumption that connectivity remains static over time. We hypothesized that relaxing stationarity assumptions would reveal novel features of both typical brain development related to children on the autism spectrum. We employed a "chronnectomic" (recurring, time-varying patterns of connectivity) approach to evaluate transient states of connectivity using resting-state functional MRI in a population-based sample of 774 6- to 10-year-old children. Dynamic connectivity was evaluated using a sliding-window approach, and revealed four transient states. Internetwork connectivity increased with age in modularized dynamic states, illustrating an important pattern of connectivity in the developing brain. Furthermore, we demonstrated that higher levels of autistic traits and ASD diagnosis were associated with longer dwell times in a globally disconnected state. These results provide a roadmap to the chronnectomic organization of the developing brain and suggest that characteristics of functional brain connectivity are related to children on the autism spectrum. © 2018 Wiley Periodicals, Inc.

Data-Driven Sequence of Changes to Anatomical Brain Connectivity in Sporadic Alzheimer's Disease.

PubMed

Oxtoby, Neil P; Garbarino, Sara; Firth, Nicholas C; Warren, Jason D; Schott, Jonathan M; Alexander, Daniel C

2017-01-01

Model-based investigations of transneuronal spreading mechanisms in neurodegenerative diseases relate the pattern of pathology severity to the brain's connectivity matrix, which reveals information about how pathology propagates through the connectivity network. Such network models typically use networks based on functional or structural connectivity in young and healthy individuals, and only end-stage patterns of pathology, thereby ignoring/excluding the effects of normal aging and disease progression. Here, we examine the sequence of changes in the elderly brain's anatomical connectivity over the course of a neurodegenerative disease. We do this in a data-driven manner that is not dependent upon clinical disease stage, by using event-based disease progression modeling. Using data from the Alzheimer's Disease Neuroimaging Initiative dataset, we sequence the progressive decline of anatomical connectivity, as quantified by graph-theory metrics, in the Alzheimer's disease brain. Ours is the first single model to contribute to understanding all three of the nature, the location, and the sequence of changes to anatomical connectivity in the human brain due to Alzheimer's disease. Our experimental results reveal new insights into Alzheimer's disease: that degeneration of anatomical connectivity in the brain may be a viable, even early, biomarker and should be considered when studying such neurodegenerative diseases.

Subtle volume differences in brain parenchyma of children surviving medulloblastoma

NASA Astrophysics Data System (ADS)

Reddick, Wilburn E.; Mulhern, Raymond K.; Elkin, T. David; Glass, John O.; Langston, James W.

1998-07-01

The overriding incentive for accurate quantification of the functional status of children treated for brain tumors emerges from the clinician's desire to balance the efficacy and chronic toxicity of therapies used for the developing child. A hybrid combination of the Kohonen self-organizing map (SOM) for segmentation and a multilayer backpropagation (MLBP) neural network for classification removes observer variances to yield a reproducible and accurate identification of tissues. A group of 17 volunteers and 77 patients from a larger ongoing study of pediatric patients with brain tumors were used to investigate the sensitivity of segmented volumes to determine atrophy as measured by two radiologists. The atrophy study revealed a significant relationship for brain parenchyma, CSF and white matter volumes with atrophy while gray matter had no significant relationship. Brain parenchyma and subsequently white matter were found to be inversely proportional to increasing grades of atrophy. An additional study compared fifteen age-matched patients treated with irradiation and surgery with patients treated with surgery alone. The age-matched study of patients demonstrated that brain volumes in the irradiated patients were significantly decreased compared to those treated with surgery alone. Further investigation of this difference revealed that white matter was significantly reduced while gray matter was relatively unchanged.

Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

PubMed

Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

2013-12-30

In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders. © 2013 Elsevier Ireland Ltd. All rights reserved.

Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

PubMed Central

Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

2015-01-01

Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

The Neonatal Connectome During Preterm Brain Development

PubMed Central

van den Heuvel, Martijn P.; Kersbergen, Karina J.; de Reus, Marcel A.; Keunen, Kristin; Kahn, René S.; Groenendaal, Floris; de Vries, Linda S.; Benders, Manon J.N.L.

2015-01-01

The human connectome is the result of an elaborate developmental trajectory. Acquiring diffusion-weighted imaging and resting-state fMRI, we studied connectome formation during the preterm phase of macroscopic connectome genesis. In total, 27 neonates were scanned at week 30 and/or week 40 gestational age (GA). Examining the architecture of the neonatal anatomical brain network revealed a clear presence of a small-world modular organization before term birth. Analysis of neonatal functional connectivity (FC) showed the early formation of resting-state networks, suggesting that functional networks are present in the preterm brain, albeit being in an immature state. Moreover, structural and FC patterns of the neonatal brain network showed strong overlap with connectome architecture of the adult brain (85 and 81%, respectively). Analysis of brain development between week 30 and week 40 GA revealed clear developmental effects in neonatal connectome architecture, including a significant increase in white matter microstructure (P < 0.01), small-world topology (P < 0.01) and interhemispheric FC (P < 0.01). Computational analysis further showed that developmental changes involved an increase in integration capacity of the connectivity network as a whole. Taken together, we conclude that hallmark organizational structures of the human connectome are present before term birth and subject to early development. PMID:24833018

Advanced lesion symptom mapping analyses and implementation as BCBtoolkit.

PubMed

Foulon, Chris; Cerliani, Leonardo; Kinkingnéhun, Serge; Levy, Richard; Rosso, Charlotte; Urbanski, Marika; Volle, Emmanuelle; Thiebaut de Schotten, Michel

2018-03-01

Patients with brain lesions provide a unique opportunity to understand the functioning of the human mind. However, even when focal, brain lesions have local and remote effects that impact functionally and structurally connected circuits. Similarly, function emerges from the interaction between brain areas rather than their sole activity. For instance, category fluency requires the associations between executive, semantic, and language production functions. Here, we provide, for the first time, a set of complementary solutions for measuring the impact of a given lesion on the neuronal circuits. Our methods, which were applied to 37 patients with a focal frontal brain lesions, revealed a large set of directly and indirectly disconnected brain regions that had significantly impacted category fluency performance. The directly disconnected regions corresponded to areas that are classically considered as functionally engaged in verbal fluency and categorization tasks. These regions were also organized into larger directly and indirectly disconnected functional networks, including the left ventral fronto-parietal network, whose cortical thickness correlated with performance on category fluency. The combination of structural and functional connectivity together with cortical thickness estimates reveal the remote effects of brain lesions, provide for the identification of the affected networks, and strengthen our understanding of their relationship with cognitive and behavioral measures. The methods presented are available and freely accessible in the BCBtoolkit as supplementary software [1].

Computer-Based Learning: Graphical Integration of Whole and Sectional Neuroanatomy Improves Long-Term Retention

PubMed Central

Naaz, Farah; Chariker, Julia H.; Pani, John R.

2013-01-01

A study was conducted to test the hypothesis that instruction with graphically integrated representations of whole and sectional neuroanatomy is especially effective for learning to recognize neural structures in sectional imagery (such as MRI images). Neuroanatomy was taught to two groups of participants using computer graphical models of the human brain. Both groups learned whole anatomy first with a three-dimensional model of the brain. One group then learned sectional anatomy using two-dimensional sectional representations, with the expectation that there would be transfer of learning from whole to sectional anatomy. The second group learned sectional anatomy by moving a virtual cutting plane through the three-dimensional model. In tests of long-term retention of sectional neuroanatomy, the group with graphically integrated representation recognized more neural structures that were known to be challenging to learn. This study demonstrates the use of graphical representation to facilitate a more elaborated (deeper) understanding of complex spatial relations. PMID:24563579

Evidence for Altered Hippocampal Volume and Brain Metabolites in Workers Occupationally Exposed to Lead: A Study by Magnetic Resonance Imaging and 1H Magnetic Resonance Spectroscopy

PubMed Central

Jiang, Yue-Ming; Long, Li-Ling; Zhu, Xia-Yan; Zheng, Hong; Fu, Xue; Ou, Shi-Yan; Wei, Dong-Lu; Zhou, Hai-Lin; Zheng, Wei

2008-01-01

Environmental and occupational exposure to lead (Pb) remains to be a major public health issue. The purpose of this cross-sectional study was to use non-invasive magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) techniques to investigate whether chronic exposure to Pb in an occupational setting altered brain structure and function of Pb-exposed workers. The Pb-exposed group consisted of 15 workers recruited from either a Pb-smelting factory or a Pb-battery manufacturer. The control group had 19 healthy volunteers who had no history of Pb exposure in working environment or at home. The average airborne Pb concentrations in fume and dust were 0.43 mg/m3 and 0.44 mg/m3, respectively in the smeltery, and 0.10 mg/m3 and 1.06 mg/m3, respectively in the Pb battery workshop. The average blood Pb concentrations (BPb) in Pb-exposed and control workers were 63.5 µg/dL and 8.7 µg/dL, respectively. The MRI examination showed that brain hippocampal volume among Pb-exposed workers was significantly diminished in comparison to age-matched control subjects (p<0.01), although the extent of this reduction was relatively small (5–6% of the control values). Linear regression analyses revealed significant inverse associations between BPb and the decreased hippocampal volume on both sides of brain hemisphere. Among five brain metabolites investigated by MRS, i.e., N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), inosine (mI), glutamate/glutamine (Glx) and lipids (Lip), a significant decrease in NAA/Cr ratio (7% of controls, p<0.05) and a remarkable increase in Lip/Cr ratio (40%, p<0.01) were observed in the brains of Pb-exposed workers as compared to controls. Furthermore, the increased Lip/Cr ratio was significantly associated with BPb (r = 0.46, p<0.01). Taken together, this study suggests that occupational exposure to Pb may cause subtle structural and functional alteration in human brains. The MRI and MRS brain imaging techniques can be used as the noninvasive means to evaluate Pb-induced neurotoxicity. PMID:18692119

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

PubMed Central

Branton, William G.; Ellestad, Kristofor K.; Maingat, Ferdinand; Wheatley, B. Matt; Rud, Erling; Warren, René L.; Holt, Robert A.; Surette, Michael G.; Power, Christopher

2013-01-01

The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12), other disease controls [ODC] (n = 14) and in cerebral surgical resections for epilepsy [SURG] (n = 6). Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4) and ODC (n = 4) patients and SURG (n = 2) groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely. Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains. Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group. Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups. Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1−/− mouse brains. Intracerebral implantation of human brain homogenates into RAG1−/− mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate. Thus, α-proteobacteria represented the major bacterial component of the primate brain’s microbiome regardless of underlying immune status, which could be transferred into naïve hosts leading to microbial persistence in the brain. PMID:23355888

Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

PubMed

Bartolomeo, Paolo; Thiebaut de Schotten, Michel

2016-12-01

Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.

PubMed

Stender, Johan; Kupers, Ron; Rodell, Anders; Thibaut, Aurore; Chatelle, Camille; Bruno, Marie-Aurélie; Gejl, Michael; Bernard, Claire; Hustinx, Roland; Laureys, Steven; Gjedde, Albert

2015-01-01

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.

Regional distribution of neuropeptide Y mRNA in postmortem human brain.

PubMed

Brené, S; Lindefors, N; Kopp, J; Sedvall, G; Persson, H

1989-12-01

The distribution of messenger RNA encoding neuropeptide Y (NPY) was studied in 11 different postmortem human brain regions using in situ hybridization histochemistry, and RNA blot analysis. In situ hybridization data revealed that the highest numerical density of labeled cells corresponded to neurons in accumbens area, caudate nucleus, putamen, and substantia innominata. Significantly fewer NPY mRNA-containing neurons were found in frontal and parietal cortex, amygdaloid body and dentate gyrus. No NPY mRNA-containing cells were found in substantia nigra. NPY mRNA-positive neurons from all regions studied showed relatively similar labeling, as revealed by computerized image analysis. Blot analysis showed an approximately 0.8 kb NPY mRNA in all brain regions studied, except in substantia nigra and cerebellum. Densitometric scanning of the autoradiograms revealed levels of NPY mRNA in the following order: putamen greater than caudate nucleus greater than frontal cortex (Brodmann areas 4 and 6) greater than temporal cortex (Brodmann area 38) greater than parietal cortex (Brodmann areas 5 and 7) greater than frontal cortex (Brodmann area 11). Hence, although NPY mRNA is widely distributed in neurons of the human brain large regional variation exists, with the highest expression in accumbens area and parts of the basal ganglia.

New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy.

PubMed

Hoch, M J; Chung, S; Ben-Eliezer, N; Bruno, M T; Fatterpekar, G M; Shepherd, T M

2016-06-01

Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization. © 2016 by American Journal of Neuroradiology.

Aromatase in the brain: not just for reproduction anymore.

PubMed

Garcia-Segura, L M

2008-06-01

Aromatase, the enzyme that synthesises oestrogens from androgen precursors, is expressed in the brain, where it has been classically associated with the regulation of neuroendocrine events and behaviours linked with reproduction. Recent findings, however, have revealed new unexpected roles for brain aromatase, indicating that the enzyme regulates synaptic activity, synaptic plasticity, neurogenesis and the response of neural tissue to injury, and may contribute to control nonreproductive behaviours, mood and cognition. Therefore, the function of brain aromatase is not restricted to the regulation of reproduction as previously thought.

Parvovirus associated cerebellar hypoplasia and hydrocephalus in day-old broiler chickens

USDA-ARS?s Scientific Manuscript database

Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

Activity-Based Protein Profiling of Organophosphorus and Thiocarbamate Pesticides Reveals Multiple Serine Hydrolase Targets in Mouse Brain

PubMed Central

NOMURA, DANIEL K.; CASIDA, JOHN E.

2010-01-01

Organophosphorus (OP) and thiocarbamate (TC) agrochemicals are used worldwide as insecticides, herbicides, and fungicides, but their safety assessment in terms of potential off-targets remains incomplete. In this study, we used a chemoproteomic platform, termed activity-based protein profiling, to broadly define serine hydrolase targets in mouse brain of a panel of 29 OP and TC pesticides. Among the secondary targets identified, enzymes involved in degradation of endocannabinoid signaling lipids, monoacylglycerol lipase and fatty acid amide hydrolase, were inhibited by several OP and TC pesticides. Blockade of these two enzymes led to elevations in brain endocannabinoid levels and dysregulated brain arachidonate metabolism. Other secondary targets include enzymes thought to also play important roles in the nervous system and unannotated proteins. This study reveals a multitude of secondary targets for OP and TC pesticides and underscores the utility of chemoproteomic platforms in gaining insights into biochemical pathways that are perturbed by these toxicants. PMID:21341672

Brain response to taste in overweight children: A pilot feasibility study.

PubMed

Bohon, Cara

2017-01-01

Understanding the neural response to food and food cues during early stages of weight gain in childhood may help us determine the drive processes involved in unhealthy eating behavior and risk for obesity. Healthy weight and overweight children ages 6-8 (N = 18; 10 with BMI between 5th and 85th %ile and 8 with BMI >85th %ile) underwent fMRI scans while anticipating and receiving tastes of chocolate milkshake. Parents completed a Children's Eating Behaviour Questionnaire. Results reveal greater response to milkshake taste receipt in overweight children in the right insula, operculum, precentral gyrus, and angular gyrus, and bilateral precuneus and posterior cingulate. No group differences were found for brain response to a visual food cue. Exploratory analyses revealed interactions between self-report measures of eating behavior and weight status on brain response to taste. This pilot study provides preliminary evidence of feasibility of studying young children's taste processing and suggests a possible developmental shift in brain response to taste.

Brain response to taste in overweight children: A pilot feasibility study

PubMed Central

Bohon, Cara

2017-01-01

Understanding the neural response to food and food cues during early stages of weight gain in childhood may help us determine the drive processes involved in unhealthy eating behavior and risk for obesity. Healthy weight and overweight children ages 6–8 (N = 18; 10 with BMI between 5th and 85th %ile and 8 with BMI >85th %ile) underwent fMRI scans while anticipating and receiving tastes of chocolate milkshake. Parents completed a Children’s Eating Behaviour Questionnaire. Results reveal greater response to milkshake taste receipt in overweight children in the right insula, operculum, precentral gyrus, and angular gyrus, and bilateral precuneus and posterior cingulate. No group differences were found for brain response to a visual food cue. Exploratory analyses revealed interactions between self-report measures of eating behavior and weight status on brain response to taste. This pilot study provides preliminary evidence of feasibility of studying young children’s taste processing and suggests a possible developmental shift in brain response to taste. PMID:28235080

Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation.

PubMed

Massa, Roberto; Pozzessere, Simone; Rastelli, Emanuele; Serra, Laura; Terracciano, Chiara; Gibellini, Manuela; Bozzali, Marco; Arca, Marcello

2016-04-01

Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment. Quantitative brain MRI with voxel-based morphometry and extended neuropsychological assessment were performed. In parallel, the coding sequences and intron/exon boundaries of the PNPLA2 gene were screened by direct sequencing. Neuropsychological assessment revealed global cognitive impairment, and brain MRI showed reduced gray matter volume in the temporal lobes. Molecular characterization revealed a novel homozygous mutation in exon 5 of PNPLA2 (c.714C>A), resulting in a premature stop codon (p.Cys238*). Some PNPLA2 mutations, such as the one described here, may present with an extended phenotype, including brain involvement. In these cases, complete neuropsychological testing, combined with quantitative brain MRI, may help to characterize and quantify cognitive impairment. © 2016 Wiley Periodicals, Inc.

Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

PubMed

Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

2013-09-15

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex.

PubMed

Guadalupe, Tulio; Mathias, Samuel R; vanErp, Theo G M; Whelan, Christopher D; Zwiers, Marcel P; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A; Arias-Vásquez, Alejandro; Aribisala, Benjamin S; Armstrong, Nicola J; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E; Baune, Bernhard T; Blangero, John; Bokde, Arun L W; Boedhoe, Premika S W; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Büchel, Christian; Buitelaar, Jan; Calhoun, Vince D; Cannon, Dara M; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; de Zubicaray, Greig I; de Zwarte, Sonja M C; Deary, Ian J; Desrivières, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dørum, Erlend S; Ehrlich, Stefan; Espeseth, Thomas; Fernández, Guillén; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jürgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U; Heinz, Andreas; Hibar, Derrek P; Hoekstra, Pieter J; Hoogman, Martine; Howells, Fleur M; Hu, Hao; Hulshoff Pol, Hilleke E; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jönsson, Erik G; Jurk, Sarah; Kahn, Rene S; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L; Medland, Sarah E; Menchón, José M; Morris, Derek W; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C; Nees, Frauke; Nordvik, Jan E; Onnink, A Marten H; Opel, Nils; Ophoff, Roel; Paillère Martinot, Marie-Laure; Papadopoulos Orfanos, Dimitri; Pauli, Paul; Paus, Tomáš; Poustka, Luise; Reddy, Janardhan Yc; Renteria, Miguel E; Roiz-Santiáñez, Roberto; Roos, Annerine; Royle, Natalie A; Sachdev, Perminder; Sánchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N; Soares, Jair C; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Toro, Roberto; Turner, Jessica A; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernández, Maria Valdés; van den Heuvel, Odile A; van der Meer, Dennis; van Haren, Neeltje E M; Veltman, Dick J; Venkatasubramanian, Ganesan; Vetter, Nora C; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M; Glahn, David C; Mazoyer, Bernard; Fisher, Simon E; Francks, Clyde

2017-10-01

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.

PubMed

Yao, Zizhen; Mich, John K; Ku, Sherman; Menon, Vilas; Krostag, Anne-Rachel; Martinez, Refugio A; Furchtgott, Leon; Mulholland, Heather; Bort, Susan; Fuqua, Margaret A; Gregor, Ben W; Hodge, Rebecca D; Jayabalu, Anu; May, Ryan C; Melton, Samuel; Nelson, Angelique M; Ngo, N Kiet; Shapovalova, Nadiya V; Shehata, Soraya I; Smith, Michael W; Tait, Leah J; Thompson, Carol L; Thomsen, Elliot R; Ye, Chaoyang; Glass, Ian A; Kaykas, Ajamete; Yao, Shuyuan; Phillips, John W; Grimley, Joshua S; Levi, Boaz P; Wang, Yanling; Ramanathan, Sharad

2017-01-05

During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/β-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation

PubMed Central

Mateos, Laura; Maioli, Silvia; Ali, Zeina; Gulyás, Balázs; Winblad, Bengt; Savitcheva, Irina

2017-01-01

Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders. PMID:28213512

Repetition priming influences distinct brain systems: evidence from task-evoked data and resting-state correlations.

PubMed

Wig, Gagan S; Buckner, Randy L; Schacter, Daniel L

2009-05-01

Behavioral dissociations suggest that a single experience can separately influence multiple processing components. Here we used a repetition priming functional magnetic resonance imaging paradigm that directly contrasted the effects of stimulus and decision changes to identify the underlying brain systems. Direct repetition of stimulus features caused marked reductions in posterior regions of the inferior temporal lobe that were insensitive to whether the decision was held constant or changed between study and test. By contrast, prefrontal cortex showed repetition effects that were sensitive to the exact stimulus-to-decision mapping. Analysis of resting-state functional connectivity revealed that the dissociated repetition effects are embedded within distinct brain systems. Regions that were sensitive to changes in the stimulus correlated with perceptual cortices, whereas the decision changes attenuated activity in regions correlated with middle-temporal regions and a frontoparietal control system. These results thus explain the long-known dissociation between perceptual and conceptual components of priming by revealing how a single experience can separately influence distinct, concurrently active brain systems.

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

PubMed

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

2016-06-01

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Maturation of metabolic connectivity of the adolescent rat brain

PubMed Central

Choi, Hongyoon; Choi, Yoori; Kim, Kyu Wan; Kang, Hyejin; Hwang, Do Won; Kim, E Edmund; Chung, June-Key; Lee, Dong Soo

2015-01-01

Neuroimaging has been used to examine developmental changes of the brain. While PET studies revealed maturation-related changes, maturation of metabolic connectivity of the brain is not yet understood. Here, we show that rat brain metabolism is reconfigured to achieve long-distance connections with higher energy efficiency during maturation. Metabolism increased in anterior cerebrum and decreased in thalamus and cerebellum during maturation. When functional covariance patterns of PET images were examined, metabolic networks including default mode network (DMN) were extracted. Connectivity increased between the anterior and posterior parts of DMN and sensory-motor cortices during maturation. Energy efficiency, a ratio of connectivity strength to metabolism of a region, increased in medial prefrontal and retrosplenial cortices. Our data revealed that metabolic networks mature to increase metabolic connections and establish its efficiency between large-scale spatial components from childhood to early adulthood. Neurodevelopmental diseases might be understood by abnormal reconfiguration of metabolic connectivity and efficiency. DOI: http://dx.doi.org/10.7554/eLife.11571.001 PMID:26613413

Diffusion MRI at 25: Exploring brain tissue structure and function

PubMed Central

Bihan, Denis Le; Johansen-Berg, Heidi

2013-01-01

Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state. PMID:22120012

Analysis of acute brain slices by electron microscopy: a correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

PubMed

Loussert Fonta, Celine; Leis, Andrew; Mathisen, Cliff; Bouvier, David S; Blanchard, Willy; Volterra, Andrea; Lich, Ben; Humbel, Bruno M

2015-01-01

Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of antigenicity. Finally, an important feature of this approach is that the fluorescence of the GFP signal is preserved throughout the entire preparation process until the last step before electron microscopy. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The musical brain: brain waves reveal the neurophysiological basis of musicality in human subjects.

PubMed

Tervaniemi, M; Ilvonen, T; Karma, K; Alho, K; Näätänen, R

1997-04-18

To reveal neurophysiological prerequisites of musicality, auditory event-related potentials (ERPs) were recorded from musical and non-musical subjects, musicality being here defined as the ability to temporally structure auditory information. Instructed to read a book and to ignore sounds, subjects were presented with a repetitive sound pattern with occasional changes in its temporal structure. The mismatch negativity (MMN) component of ERPs, indexing the cortical preattentive detection of change in these stimulus patterns, was larger in amplitude in musical than non-musical subjects. This amplitude enhancement, indicating more accurate sensory memory function in musical subjects, suggests that even the cognitive component of musicality, traditionally regarded as depending on attention-related brain processes, in fact, is based on neural mechanisms present already at the preattentive level.

PET and Single-Photon Emission Computed Tomography in Brain Concussion.

PubMed

Raji, Cyrus A; Henderson, Theodore A

2018-02-01

This article offers an overview of the application of PET and single photon emission computed tomography brain imaging to concussion, a type of mild traumatic brain injury and traumatic brain injury, in general. The article reviews the application of these neuronuclear imaging modalities in cross-sectional and longitudinal studies. Additionally, this article frames the current literature with an overview of the basic physics and radiation exposure risks of each modality. Copyright © 2017 Elsevier Inc. All rights reserved.

Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

PubMed

Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

2018-05-01

The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774. © AlphaMed Press 2018.

Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent Fasting on Cognitive Performance at Rest and During Exercise in Adults.

PubMed

Cherif, Anissa; Roelands, Bart; Meeusen, Romain; Chamari, Karim

2016-01-01

The aim of this review was to highlight the potent effects of intermittent fasting on the cognitive performance of athletes at rest and during exercise. Exercise interacts with dietary factors and has a positive effect on brain functioning. Furthermore, physical activity and exercise can favorably influence brain plasticity. Mounting evidence indicates that exercise, in combination with diet, affects the management of energy metabolism and synaptic plasticity by affecting molecular mechanisms through brain-derived neurotrophic factor, an essential neurotrophin that acts at the interface of metabolism and plasticity. The literature has also shown that certain aspects of physical performance and mental health, such as coping and decision-making strategies, can be negatively affected by daylight fasting. However, there are several types of intermittent fasting. These include caloric restriction, which is distinct from fasting and allows subjects to drink water ad libitum while consuming a very low-calorie food intake. Another type is Ramadan intermittent fasting, which is a religious practice of Islam, where healthy adult Muslims do not eat or drink during daylight hours for 1 month. Other religious practices in Islam (Sunna) also encourage Muslims to practice intermittent fasting outside the month of Ramadan. Several cross-sectional and longitudinal studies have shown that intermittent fasting has crucial effects on physical and intellectual performance by affecting various aspects of bodily physiology and biochemistry that could be important for athletic success. Moreover, recent findings revealed that immunological variables are also involved in cognitive functioning and that intermittent fasting might impact the relationship between cytokine expression in the brain and cognitive deficits, including memory deficits.

Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

PubMed

Garcia-Ramos, Camille; Jackson, Daren C; Lin, Jack J; Dabbs, Kevin; Jones, Jana E; Hsu, David A; Stafstrom, Carl E; Zawadzki, Lucy; Seidenberg, Michael; Prabhakaran, Vivek; Hermann, Bruce P

2015-10-01

Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC). Participants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes. Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC. Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Cannabis use and brain structural alterations of the cingulate cortex in early psychosis.

PubMed

Rapp, Charlotte; Walter, Anna; Studerus, Erich; Bugra, Hilal; Tamagni, Corinne; Röthlisberger, Michel; Borgwardt, Stefan; Aston, Jacqueline; Riecher-Rössler, Anita

2013-11-30

As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors. © 2013 Elsevier Ireland Ltd. All rights reserved.

Population-scale three-dimensional reconstruction and quantitative profiling of microglia arbors

PubMed Central

Rey-Villamizar, Nicolas; Merouane, Amine; Lu, Yanbin; Mukherjee, Amit; Trett, Kristen; Chong, Peter; Harris, Carolyn; Shain, William; Roysam, Badrinath

2015-01-01

Motivation: The arbor morphologies of brain microglia are important indicators of cell activation. This article fills the need for accurate, robust, adaptive and scalable methods for reconstructing 3-D microglial arbors and quantitatively mapping microglia activation states over extended brain tissue regions. Results: Thick rat brain sections (100–300 µm) were multiplex immunolabeled for IBA1 and Hoechst, and imaged by step-and-image confocal microscopy with automated 3-D image mosaicing, producing seamless images of extended brain regions (e.g. 5903 × 9874 × 229 voxels). An over-complete dictionary-based model was learned for the image-specific local structure of microglial processes. The microglial arbors were reconstructed seamlessly using an automated and scalable algorithm that exploits microglia-specific constraints. This method detected 80.1 and 92.8% more centered arbor points, and 53.5 and 55.5% fewer spurious points than existing vesselness and LoG-based methods, respectively, and the traces were 13.1 and 15.5% more accurate based on the DIADEM metric. The arbor morphologies were quantified using Scorcioni’s L-measure. Coifman’s harmonic co-clustering revealed four morphologically distinct classes that concord with known microglia activation patterns. This enabled us to map spatial distributions of microglial activation and cell abundances. Availability and implementation: Experimental protocols, sample datasets, scalable open-source multi-threaded software implementation (C++, MATLAB) in the electronic supplement, and website (www.farsight-toolkit.org). http://www.farsight-toolkit.org/wiki/Population-scale_Three-dimensional_Reconstruction_and_Quanti-tative_Profiling_of_Microglia_Arbors Contact: broysam@central.uh.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701570

Two distinct events, section compression and loss of particles ("lost caps"), contribute to z-axis distortion and bias in optical disector counting.

PubMed

Baryshnikova, Larisa M; Von Bohlen Und Halbach, Oliver; Kaplan, Suleyman; Von Bartheld, Christopher S

2006-09-01

Deformation of tissue sections in the z-axis can bias optical disector counting. When samples of particle densities are not representative for the entire tissue section, significant bias of estimated numbers can result. To assess the occurrence, prevalence, extent, sequence of events, and causes of z-axis distortion, the distribution of neuronal nucleoli in thick paraffin and vibratome sections was determined in chicken, rodent, and human brain tissues. When positions of neuronal nucleoli were measured in the z-axis, nucleoli were more frequent at the surfaces (bottom and top) of tissue sections than in the core. This nonlinear z-axis distribution was not lab-, equipment-, or investigator-specific, and was independent of age, fixation quality, coverslipping medium, or paraffin melting temperature, but in paraffin sections, was highly correlated with the tilt of the knife (cutting) angle. Manipulation of subsequent tissue processing steps revealed that two events contribute to z-axis distortion. Initially, a higher density of particles results at surfaces after sectioning, apparently due to section compression. Subsequently, particles can be lost to varying degrees from surfaces during floating or staining and dehydration, resulting in "lost caps." These results may explain different degrees of z-axis distortion between different types of sections and different labs, and reinforce the importance of checking z-axis distributions as a "quality control" prior to selection of guard zones in optical disector counting. Indirect approaches to assess section quality, such as resectioning in a perpendicular plane, yield additional artifacts, and should be replaced by a direct quantitative measurement of z-axis distribution of particles. (c) 2006 Wiley-Liss, Inc.

Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

PubMed

Jamrozik, Z; Lugowska, A; Gołębiowski, M; Królicki, L; Mączewska, J; Kuźma-Kozakiewicz, M

2013-09-25

A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. © 2013 Elsevier B.V. All rights reserved.

[Comparative rheoencephalographic and convective radiation encephalic thermometric studies].

PubMed

Vaĭsfel'd, D N; Korobov, S A; Petrov, A P

1996-01-01

It is for the first time that thermoassimetry of heart flows of brain right and left hemispheres presenting as predominance of radiative-convective heat radiation from the left has been revealed, the thermoassimetry gradient being rostral-caudal. Disclosed in cerebral hemispheres was complimentarity of energetic processes: the right hemisphere secures the background energy state, the left one functions in ensuring the discrete adaptive thermoenergy reactions. The thermoassimetry revealed may be the basis of other functional asymmetries of the brain. There was no parallelism between the studied parameters of circulation and heat flow.

Research on terahertz properties of rat brain tissue sections during dehydration

NASA Astrophysics Data System (ADS)

Cui, Gangqiang; Liang, Jianfeng; Zhao, Hongwei; Zhao, Xianghui; Chang, Chao

2018-01-01

Biological tissue sections are always kept in a system purged with dry nitrogen for the measurement of terahertz spectrum. However, the injected nitrogen will cause dehydration of tissue sections, which will affect the accuracy of spectrum measurement. In this paper, terahertz time-domain spectrometer is used to measure the terahertz spectra of rat brain tissue sections during dehydration. The changes of terahertz properties, including terahertz transmittance, refractive index and extinction coefficient during dehydration are also analyzed. The amplitudes of terahertz time-domain spectra increase gradually during the dehydration process. Besides, the terahertz properties show obvious changes during the dehydration process. All the results indicate that the injected dry nitrogen has a significant effect on the terahertz spectra and properties of tissue sections. This study contributes to further research and application of terahertz technology in biomedical field.

Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study.

PubMed

Baseri, Babak; Choi, James J; Tung, Yao-Sheng; Konofagou, Elisa E

2010-09-01

As a potentially viable method of brain drug delivery, the safety profile of blood-brain barrier (BBB) opening using focused ultrasound (FUS) and ultrasound contrast agents (UCA) needs to be established. In this study, we provide a short-term (30-min or 5-h survival) histological assessment of murine brains undergoing FUS-induced BBB opening. Forty-nine mice were intravenously injected with Definity microbubbles (0.05 microL/kg) and sonicated under the following parameters: frequency of 1.525 MHz, pulse length of 20 ms, pulse repetition frequency of 10 Hz, peak rarefactional acoustic pressures of 0.15-0.98 MPa and two 30-s sonication intervals with an intermittent 30-s delay. The BBB opening threshold was found to be 0.15-0.3 MPa based on fluorescence and magnetic resonance imaging of systemically injected tracers. Analysis of three histological measures in hematoxylin and eosin-stained sections revealed the safest acoustic pressure to be within the range of 0.3-0.46 MPa in all examined time periods post sonication. Across different pressure amplitudes, only the samples 30 min post opening showed significant difference (p < 0.05) in the average number of distinct damaged sites, microvacuolated sites, dark neurons and sites with extravasated erythrocytes. Enhanced fluorescence around severed microvessels was also noted and found to be associated with the largest tissue effects, whereas mildly diffuse BBB opening with uniform fluorescence in the parenchyma was associated with no or mild tissue injury. Region-specific areas of the sonicated brain (thalamus, hippocampal fissure, dentate gyrus and CA3 area of hippocampus) exhibited variation in fluorescence intensity based on the position, orientation and size of affected vessels. The results of this short-term histological analysis demonstrated the feasibility of a safe FUS-UCA-induced BBB opening under a specific set of sonication parameters and provided new insights on the mechanism of BBB opening.

[Immunocytochemical demonstration of astrocytes in brain sections combined with Nissl staining].

PubMed

Korzhevskiĭ, D E; Otellin, V A

2004-01-01

The aim of the present study was to develop an easy and reliable protocol of combined preparation staining, which would unite the advantages of immunocytochemical demonstration of astrocytes with the availability to evaluate functional state of neurons provided by Nissl technique. The presented protocol of paraffin sections processing allows to retain high quality of tissue structure and provides for selective demonstration of astrocytes using the monoclonal antibodies against glial fibrillary acidic protein and contrast Nissl staining of cells. The protocol can be used without any changes for processing of brain sections obtained from the humans and other mammals with the exception of mice and rabbits.

Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment.

PubMed

Mito, Remika; Raffelt, David; Dhollander, Thijs; Vaughan, David N; Tournier, J-Donald; Salvado, Olivier; Brodtmann, Amy; Rowe, Christopher C; Villemagne, Victor L; Connelly, Alan

2018-01-04

Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixel-based analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i.e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Utility of the Mayo-Portland Adaptability Inventory Participation Index (M2PI) in US Military Veterans With a History of Mild Traumatic Brain Injury.

PubMed

OʼRourke, Justin; Critchfield, Edan; Soble, Jason; Bain, Kathleen; Fullen, Chrystal; Eapen, Blessen

2018-05-31

To examine the utility of the Mayo-Portland Adaptability Inventory-4th Edition Participation Index (M2PI) as a self-report measure of functional outcome following mild traumatic brain injury (mTBI) in US Military veterans. Department of Veterans Affairs Polytrauma Rehabilitation Center specialty hospital. On hundred thirty-nine veterans with a history of self-reported mTBI. Retrospective cross-sectional examination of data collected from regular clinical visits. M2PI, Neurobehavioral Symptoms Inventory with embedded validity measures, Posttraumatic Stress Disorder Checklist-Military Version. Forty-one percent of the sample provided symptom reports that exceeded established cut scores on embedded symptom validity tests. Invalid responders had higher levels of unemployment and endorsed significantly greater functional impairment, posttraumatic stress symptoms, and postconcussive complaints. For valid responders, regression analyses revealed that self-reported functioning was primarily related to posttraumatic stress complaints, followed by postconcussive cognitive complaints. For invalid responders, posttraumatic stress complaints also predicted self-reported functioning. Caution is recommended when utilizing the M2PI to measure functional outcome following mTBI in military veterans, particularly in the absence of symptom validity tests.

Differences in navigation performance and postpartal striatal volume associated with pregnancy in humans.

PubMed

Lisofsky, Nina; Wiener, Jan; de Condappa, Olivier; Gallinat, Jürgen; Lindenberger, Ulman; Kühn, Simone

2016-10-01

Pregnancy is accompanied by prolonged exposure to high estrogen levels. Animal studies have shown that estrogen influences navigation strategies and, hence, affects navigation performance. High estrogen levels are related to increased use of hippocampal-based allocentric strategies and decreased use of striatal-based egocentric strategies. In humans, associations between hormonal shifts and navigation strategies are less well studied. This study compared 30 peripartal women (mean age 28years) to an age-matched control group on allocentric versus egocentric navigation performance (measured in the last month of pregnancy) and gray matter volume (measured within two months after delivery). None of the women had a previous pregnancy before study participation. Relative to controls, pregnant women performed less well in the egocentric condition of the navigation task, but not the allocentric condition. A whole-brain group comparison revealed smaller left striatal volume (putamen) in the peripartal women. Across the two groups, left striatal volume was associated with superior egocentric over allocentric performance. Limited by the cross-sectional study design, the findings are a first indication that human pregnancy might be accompanied by structural brain changes in navigation-related neural systems and concomitant changes in navigation strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

NASA Astrophysics Data System (ADS)

Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

2014-09-01

Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

[Pyramidal syndrome in lateral amyotrophic sclerosis: clinico-morphological analysis].

PubMed

Musaeva, L S; Zavalishin, I A; Gulevskaia, T S

2003-01-01

Retrospective clinical analysis with a special focus on pyramidal syndrome expression in the disease course as well as morphological study of brain and spinal structures in all levels of cortical-spinal projection (from brain motor cortex to spinal lumbar segments) have been conducted for 11 section cases of lateral amyotrophic sclerosis (LAS), sporadic type. Two groups of patients were studied: with pronounced pyramidal syndrome (spasticity, hyperreflexia, etc)--7 cases and with some signs of pyramidal deficiency (anisoreflexia, stability of peritoneal reflexes)--4 cases. Pyramidal syndrome in LAS is considered as an emergence of current neurodegenerative process, embracing a significant part of upper motor neurons of both precentral convolution and its axons along the whole length of cerebrospinal axis in the form of cytoplasmic inclusions and axonal spheroids. A presence of pathomorphological changes in other upper segmental structures of motor control reveals their role in pyramidal deficiency. Comparative analysis showed that expression of pyramidal syndrome signs and its correlation to atrophic paresis appearances is specifically determined by the severity of upper and lower motor neurons lesions. With regard to morphological changes in CNS structures, the peculiarities of some pyramidal syndrome appearances in LAS are analyzed.

Not only cardiovascular, but also coordinative exercise increases hippocampal volume in older adults

PubMed Central

Niemann, Claudia; Godde, Ben; Voelcker-Rehage, Claudia

2014-01-01

Cardiovascular activity has been shown to be positively associated with gray and white matter volume of, amongst others, frontal and temporal brain regions in older adults. This is particularly true for the hippocampus, a brain structure that plays an important role in learning and memory, and whose decline has been related to the development of Alzheimer’s disease. In the current study, we were interested in whether not only cardiovascular activity but also other types of physical activity, i.e., coordination training, were also positively associated with the volume of the hippocampus in older adults. For this purpose we first collected cross-sectional data on “metabolic fitness” (cardiovascular fitness and muscular strength) and “motor fitness” (e.g., balance, movement speed, fine coordination). Second, we performed a 12-month randomized controlled trial. Results revealed that motor fitness but not metabolic fitness was associated with hippocampal volume. After the 12-month intervention period, both, cardiovascular and coordination training led to increases in hippocampal volume. Our findings suggest that a high motor fitness level as well as different types of physical activity were beneficial to diminish age-related hippocampal volume shrinkage or even increase hippocampal volume. PMID:25165446

Neuroimaging Findings from Childhood Onset Schizophrenia Patients and their Non-Psychotic Siblings

PubMed Central

Ordóñez, Anna E.; Luscher, Zoe; Gogtay, Nitin

2015-01-01

Childhood onset schizophrenia (COS), with onset of psychosis before age 13, is a rare form of schizophrenia that represents a more severe and chronic form of the adult onset illness. In this review we examine structural and functional magnetic resonance imaging (MRI) studies of COS and non-psychotic siblings of COS patients in the context of studies of schizophrenia as a whole. Studies of COS to date reveal progressive loss of gray matter volume and cortical thinning, ventricular enlargement, progressive decline in cerebellar volume and a significant but fixed deficit in hippocampal volume. COS is also associated with a slower rate of white matter growth and disrupted local connectivity strength. Sibling studies indicate that non-psychotic siblings of COS patients share many of these brain abnormalities, including decreased cortical thickness and disrupted white matter growth, yet these abnormalities normalize with age. Cross-sectional and longitudinal neuroimaging studies remain some of the few methods for assessing human brain function and play a pivotal role in the quest for understanding the neurobiology of schizophrenia as well as other psychiatric disorders. Parallel studies in non-psychotic siblings provide a unique opportunity to understand both risk and resilience in schizophrenia. PMID:25819937

Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings.

PubMed

Ordóñez, Anna E; Luscher, Zoe I; Gogtay, Nitin

2016-06-01

Childhood onset schizophrenia (COS), with onset of psychosis before age 13, is a rare form of schizophrenia that represents a more severe and chronic form of the adult onset illness. In this review we examine structural and functional magnetic resonance imaging (MRI) studies of COS and non-psychotic siblings of COS patients in the context of studies of schizophrenia as a whole. Studies of COS to date reveal progressive loss of gray matter volume and cortical thinning, ventricular enlargement, progressive decline in cerebellar volume and a significant but fixed deficit in hippocampal volume. COS is also associated with a slower rate of white matter growth and disrupted local connectivity strength. Sibling studies indicate that non-psychotic siblings of COS patients share many of these brain abnormalities, including decreased cortical thickness and disrupted white matter growth, yet these abnormalities normalize with age. Cross-sectional and longitudinal neuroimaging studies remain some of the few methods for assessing human brain function and play a pivotal role in the quest for understanding the neurobiology of schizophrenia as well as other psychiatric disorders. Parallel studies in non-psychotic siblings provide a unique opportunity to understand both risk and resilience in schizophrenia. Published by Elsevier B.V.

Flexible modulation of network connectivity related to cognition in Alzheimer's disease.

PubMed

McLaren, Donald G; Sperling, Reisa A; Atri, Alireza

2014-10-15

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Mapping social behavior-induced brain activation at cellular resolution in the mouse

PubMed Central

Kim, Yongsoo; Venkataraju, Kannan Umadevi; Pradhan, Kith; Mende, Carolin; Taranda, Julian; Turaga, Srinivas C.; Arganda-Carreras, Ignacio; Ng, Lydia; Hawrylycz, Michael J.; Rockland, Kathleen; Seung, H. Sebastian; Osten, Pavel

2014-01-01

Understanding how brain activation mediates behaviors is a central goal of systems neuroscience. Here we apply an automated method for mapping brain activation in the mouse in order to probe how sex-specific social behaviors are represented in the male brain. Our method uses the immediate early gene c-fos, a marker of neuronal activation, visualized by serial two-photon tomography: the c-fos-GFP-positive neurons are computationally detected, their distribution is registered to a reference brain and a brain atlas, and their numbers are analyzed by statistical tests. Our results reveal distinct and shared female and male interaction-evoked patterns of male brain activation representing sex discrimination and social recognition. We also identify brain regions whose degree of activity correlates to specific features of social behaviors and estimate the total numbers and the densities of activated neurons per brain areas. Our study opens the door to automated screening of behavior-evoked brain activation in the mouse. PMID:25558063

Analysis and asynchronous detection of gradually unfolding errors during monitoring tasks

NASA Astrophysics Data System (ADS)

Omedes, Jason; Iturrate, Iñaki; Minguez, Javier; Montesano, Luis

2015-10-01

Human studies on cognitive control processes rely on tasks involving sudden-onset stimuli, which allow the analysis of these neural imprints to be time-locked and relative to the stimuli onset. Human perceptual decisions, however, comprise continuous processes where evidence accumulates until reaching a boundary. Surpassing the boundary leads to a decision where measured brain responses are associated to an internal, unknown onset. The lack of this onset for gradual stimuli hinders both the analyses of brain activity and the training of detectors. This paper studies electroencephalographic (EEG)-measurable signatures of human processing for sudden and gradual cognitive processes represented as a trajectory mismatch under a monitoring task. Time-locked potentials and brain-source analysis of the EEG of sudden mismatches revealed the typical components of event-related potentials and the involvement of brain structures related to cognitive control processing. For gradual mismatch events, time-locked analyses did not show any discernible EEG scalp pattern, despite related brain areas being, to a lesser extent, activated. However, and thanks to the use of non-linear pattern recognition algorithms, it is possible to train an asynchronous detector on sudden events and use it to detect gradual mismatches, as well as obtaining an estimate of their unknown onset. Post-hoc time-locked scalp and brain-source analyses revealed that the EEG patterns of detected gradual mismatches originated in brain areas related to cognitive control processing. This indicates that gradual events induce latency in the evaluation process but that similar brain mechanisms are present in sudden and gradual mismatch events. Furthermore, the proposed asynchronous detection model widens the scope of applications of brain-machine interfaces to other gradual processes.

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

PubMed

Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hyo-Jeong; Huh, Yang Hoon; Cho, Seong-Wan; Lee, Jin-Koo; Kim, Hyung-Gun; Kim, Hak Rim

2018-01-01

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

Increased densities of monocarboxylate transport protein MCT1 after chronic administration of nicotine in rat brain.

PubMed

Canis, Martin; Mack, Brigitte; Gires, Olivier; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

2009-08-01

Chronic administration of nicotine is followed by a general stimulation of brain metabolism that results in a distinct increase of glucose transport protein densities for Glut1 and Glu3, and local cerebral glucose utilization (LCGU). This increase of LCGU might be paralleled by an enhanced production of lactate. Therefore, the question arose as to whether chronic nicotine infusion is accompanied by increased local densities of monocarboxylate transporter MCT1 in the brain. Secondly, we inquired whether LCGU might be correlated with local densities of MCT1 during normal conditions and after chronic nicotine infusion. Nicotine was given subcutaneously for 1 week by osmotic mini-pumps and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. MCT1 density was significantly increased in 21 of 32 brain structures investigated (median increase 15.0+/-3.6%). Immunohistochemical stainings of these substructures revealed an over-expression of MCT1 within endothelial cells and astrocytes of treated animals. A comparison of 23 MCT1 densities with LCGU measured in the same structures in a previous study revealed a partial correlation between both parameters under control conditions and after chronic nicotine infusion. 10 out of 23 brain areas, which showed a significant increase of MCT1 density due to chronic nicotine infusion, also showed a significant increase of LCGU. In summary, our data show that chronic nicotine infusion induces a moderate increase of local and global density of MCT1 in defined brain structures. However, in terms of brain topologies and substructures this phenomenon did partially match with increased LCGU. It is concluded that MCT1 transporters were upregulated during chronic nicotine infusion at the level of brain substructures and, at least partially, independently of LCGU.

Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

PubMed

Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

2013-02-01

Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright © 2012 John Wiley & Sons, Ltd.

Small-worldness and gender differences of large scale brain metabolic covariance networks in young adults: a FDG PET study of 400 subjects.

PubMed

Hu, Yuxiao; Xu, Qiang; Shen, Junkang; Li, Kai; Zhu, Hong; Zhang, Zhiqiang; Lu, Guangming

2015-02-01

Many studies have demonstrated the small-worldness of the human brain, and have revealed a sexual dimorphism in brain network properties. However, little is known about the gender effects on the topological organization of the brain metabolic covariance networks. To investigate the small-worldness and the gender differences in the topological architectures of human brain metabolic networks. FDG-PET data of 400 healthy right-handed subjects (200 women and 200 age-matched men) were involved in the present study. Metabolic networks of each gender were constructed by calculating the covariance of regional cerebral glucose metabolism (rCMglc) across subjects on the basis of AAL parcellation. Gender differences of network and nodal properties were investigated by using the graph theoretical approaches. Moreover, the gender-related difference of rCMglc in each brain region was tested for investigating the relationships between the hub regions and the brain regions showing significant gender-related differences in rCMglc. We found prominent small-world properties in the domain of metabolic networks in each gender. No significant gender difference in the global characteristics was found. Gender differences of nodal characteristic were observed in a few brain regions. We also found bilateral and lateralized distributions of network hubs in the females and males. Furthermore, we first reported that some hubs of a gender located in the brain regions showing weaker rCMglc in this gender than the other gender. The present study demonstrated that small-worldness was existed in metabolic networks, and revealed gender differences of organizational patterns in metabolic network. These results maybe provided insights into the understanding of the metabolic substrates underlying individual differences in cognition and behaviors. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

Dorsal and ventral stream contributions to form-from-motion perception in a patient with form-from motion deficit: a case report.

PubMed

Mercier, Manuel R; Schwartz, Sophie; Spinelli, Laurent; Michel, Christoph M; Blanke, Olaf

2017-03-01

The main model of visual processing in primates proposes an anatomo-functional distinction between the dorsal stream, specialized in spatio-temporal information, and the ventral stream, processing essentially form information. However, these two pathways also communicate to share much visual information. These dorso-ventral interactions have been studied using form-from-motion (FfM) stimuli, revealing that FfM perception first activates dorsal regions (e.g., MT+/V5), followed by successive activations of ventral regions (e.g., LOC). However, relatively little is known about the implications of focal brain damage of visual areas on these dorso-ventral interactions. In the present case report, we investigated the dynamics of dorsal and ventral activations related to FfM perception (using topographical ERP analysis and electrical source imaging) in a patient suffering from a deficit in FfM perception due to right extrastriate brain damage in the ventral stream. Despite the patient's FfM impairment, both successful (observed for the highest level of FfM signal) and absent/failed FfM perception evoked the same temporal sequence of three processing states observed previously in healthy subjects. During the first period, brain source localization revealed cortical activations along the dorsal stream, currently associated with preserved elementary motion processing. During the latter two periods, the patterns of activity differed from normal subjects: activations were observed in the ventral stream (as reported for normal subjects), but also in the dorsal pathway, with the strongest and most sustained activity localized in the parieto-occipital regions. On the other hand, absent/failed FfM perception was characterized by weaker brain activity, restricted to the more lateral regions. This study shows that in the present case report, successful FfM perception, while following the same temporal sequence of processing steps as in normal subjects, evoked different patterns of brain activity. By revealing a brain circuit involving the most rostral part of the dorsal pathway, this study provides further support for neuro-imaging studies and brain lesion investigations that have suggested the existence of different brain circuits associated with different profiles of interaction between the dorsal and the ventral streams.

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

PubMed

Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-06-11

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018 Elsevier B.V. All rights reserved.

A Program for Solving the Brain Ischemia Problem

PubMed Central

DeGracia, Donald J.

2013-01-01

Our recently described nonlinear dynamical model of cell injury is here applied to the problems of brain ischemia and neuroprotection. We discuss measurement of global brain ischemia injury dynamics by time course analysis. Solutions to proposed experiments are simulated using hypothetical values for the model parameters. The solutions solve the global brain ischemia problem in terms of “master bifurcation diagrams” that show all possible outcomes for arbitrary durations of all lethal cerebral blood flow (CBF) decrements. The global ischemia master bifurcation diagrams: (1) can map to a single focal ischemia insult, and (2) reveal all CBF decrements susceptible to neuroprotection. We simulate measuring a neuroprotectant by time course analysis, which revealed emergent nonlinear effects that set dynamical limits on neuroprotection. Using over-simplified stroke geometry, we calculate a theoretical maximum protection of approximately 50% recovery. We also calculate what is likely to be obtained in practice and obtain 38% recovery; a number close to that often reported in the literature. The hypothetical examples studied here illustrate the use of the nonlinear cell injury model as a fresh avenue of approach that has the potential, not only to solve the brain ischemia problem, but also to advance the technology of neuroprotection. PMID:24961411

Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

DTIC Science & Technology

2011-06-02

hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging ( DTI ), an advanced form of magnetic... DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mecha- nism of injury (e.g...other injuries but no clinical diagnosis of traumatic brain injury. Results Abnormalities revealed on DTI were consistent with traumatic axonal injury in

Identifying and Solving the Real Problems Facing the Integrated Disability Evaluation System (IDES)

DTIC Science & Technology

2013-06-14

future. Statistics from the Defense and Veterans Brain Injury Center reveal that, from 2000 to mid 2012, 34 there were 244,217 medical diagnoses...of Traumatic Brain Injury, of which 46,795 were moderate to severe/penetrating. While 84 percent of those injuries were not deployment related, such...injuries represent a significant issue for the health of the force (Defense and Veterans Brain Injury Center 2012). Similarly, a 2010 Congressional

Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

NASA Astrophysics Data System (ADS)

Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

2015-12-01

Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

Brain structure differences between Chinese and Caucasian cohorts: A comprehensive morphometry study.

PubMed

Tang, Yuchun; Zhao, Lu; Lou, Yunxia; Shi, Yonggang; Fang, Rui; Lin, Xiangtao; Liu, Shuwei; Toga, Arthur

2018-05-01

Numerous behavioral observations and brain function studies have demonstrated that neurological differences exist between East Asians and Westerners. However, the extent to which these factors relate to differences in brain structure is still not clear. As the basis of brain functions, the anatomical differences in brain structure play a primary and critical role in the origination of functional and behavior differences. To investigate the underlying differences in brain structure between the two cultural/ethnic groups, we conducted a comparative study on education-matched right-handed young male adults (age = 22-29 years) from two cohorts, Han Chinese (n = 45) and Caucasians (n = 45), using high-dimensional structural magnetic resonance imaging (MRI) data. Using two well-validated imaging analysis techniques, surface-based morphometry (SBM) and voxel-based morphometry (VBM), we performed a comprehensive vertex-wise morphometric analysis of the brain structures between Chinese and Caucasian cohorts. We identified consistent significant between-group differences in cortical thickness, volume, and surface area in the frontal, temporal, parietal, occipital, and insular lobes as well as the cingulate cortices. The SBM analyses revealed that compared with Caucasians, the Chinese population showed larger cortical structures in the temporal and cingulate regions, and smaller structural measures in the frontal and parietal cortices. The VBM data of the same sample was well-aligned with the SBM findings. Our findings systematically revealed comprehensive brain structural differences between young male Chinese and Caucasians, and provided new neuroanatomical insights to the behavioral and functional distinctions in the two cultural/ethnic populations. © 2018 Wiley Periodicals, Inc.

Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

PubMed Central

Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T. D.; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N.; DiPerna, Danielle M.; Paquette, Kimberly M.; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F.; Liotta, Lance A.; Ramanathan, Ramesh K.; Berens, Michael E.; Tran, Nhan L.

2014-01-01

The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. PMID:24489661

Progressive gender differences of structural brain networks in healthy adults: a longitudinal, diffusion tensor imaging study.

PubMed

Sun, Yu; Lee, Renick; Chen, Yu; Collinson, Simon; Thakor, Nitish; Bezerianos, Anastasios; Sim, Kang

2015-01-01

Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical "small-world" architecture (high local clustering and short paths between nodes). Additional analysis revealed a more economical "small-world" architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus) exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders.

Gaining insight of fetal brain development with diffusion MRI and histology.

PubMed

Huang, Hao; Vasung, Lana

2014-02-01

Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic levels. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Dapsone protects brain microvascular integrity from high-fat diet induced LDL oxidation.

PubMed

Zhan, Rui; Zhao, Mingming; Zhou, Ting; Chen, Yue; Yu, Weiwei; Zhao, Lei; Zhang, Tao; Wang, Hecheng; Yang, Huan; Jin, Yinglan; He, Qihua; Yang, Xiaoda; Guo, Xiangyang; Willard, Belinda; Pan, Bing; Huang, Yining; Chen, Yingyu; Chui, Dehua; Zheng, Lemin

2018-06-07

Atherosclerosis was considered to induce many vascular-related complications, such as acute myocardial infarction and stroke. Abnormal lipid metabolism and its peroxidation inducing blood-brain barrier (BBB) leakage were associated with the pre-clinical stage of stroke. Dapsone (DDS), an anti-inflammation and anti-oxidation drug, has been found to have protective effects on vascular. However, whether DDS has a protective role on brain microvessels during lipid oxidation had yet to be elucidated. We investigated brain microvascular integrity in a high-fat diet (HFD) mouse model. We designed this study to explore whether DDS had protective effects on brain microvessels under lipid oxidation and tried to explain the underlying mechanism. In our live optical study, we found that DDS significantly attenuated brain microvascular leakage through reducing serum oxidized low-density lipoprotein (oxLDL) in HFD mice (p < 0.001), and DDS significantly inhibited LDL oxidation in vitro (p < 0.001). Our study showed that DDS protected tight junction proteins: ZO-1 (p < 0.001), occludin (p < 0.01), claudin-5 (p < 0.05) of microvascular endothelial cells in vivo and in vitro. DDS reversed LAMP1 aggregation in cytoplasm, and decreased the destruction of tight junction protein: ZO-1 in vitro. We first revealed that DDS had a protective role on cerebral microvessels through preventing tight junction ZO-1 from abnormal degradation by autophagy and reducing lysosome accumulation. Our findings suggested the significance of DDS in protecting brain microvessels under lipid metabolic disorders, which revealed a novel potential therapeutic strategy in brain microvascular-related diseases.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation.

PubMed

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-08

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a 'false-negative' result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation

PubMed Central

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-01

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a ‘false-negative’ result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death. PMID:23302550

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

PubMed

Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

2017-12-15

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

Evaluation of TgH(CX3CR1-EGFP) mice implanted with mCherry-GL261 cells as an in vivo model for morphometrical analysis of glioma-microglia interaction.

PubMed

Resende, Fernando F B; Bai, Xianshu; Del Bel, Elaine Aparecida; Kirchhoff, Frank; Scheller, Anja; Titze-de-Almeida, Ricardo

2016-02-08

Glioblastoma multiforme is the most aggressive brain tumor. Microglia are prominent cells within glioma tissue and play important roles in tumor biology. This work presents an animal model designed for the study of microglial cell morphology in situ during gliomagenesis. It also allows a quantitative morphometrical analysis of microglial cells during their activation by glioma cells. The animal model associates the following cell types: 1- mCherry red fluorescent GL261 glioma cells and; 2- EGFP fluorescent microglia, present in the TgH(CX3CR1-EGFP) mouse line. First, mCherry-GL261 glioma cells were implanted in the brain cortex of TgH(CX3CR1-EGFP) mice. Epifluorescence - and confocal laser-scanning microscopy were employed for analysis of fixed tissue sections, whereas two-photon laser-scanning microscopy (2P-LSM) was used to track tumor cells and microglia in the brain of living animals. Implanted mCherry-GL261 cells successfully developed brain tumors. They mimic the aggressive behavior found in human disease, with a rapid increase in size and the presence of secondary tumors apart from the injection site. As tumor grows, mCherry-GL261 cells progressively lost their original shape, adopting a heterogeneous and diffuse morphology at 14-18 d. Soma size increased from 10-52 μm. At this point, we focused on the kinetics of microglial access to glioma tissues. 2P-LSM revealed an intense microgliosis in brain areas already shortly after tumor implantation, i.e. at 30 min. By confocal microscopy, we found clusters of microglial cells around the tumor mass in the first 3 days. Then cells infiltrated the tumor area, where they remained during all the time points studied, from 6-18 days. Microglia in contact with glioma cells also present changes in cell morphology, from a ramified to an amoeboid shape. Cell bodies enlarged from 366 ± 0.0 μm(2), in quiescent microglia, to 1310 ± 146.0 μm(2), and the cell processes became shortened. The GL261/CX3CR1 mouse model reported here is a valuable tool for imaging of microglial cells during glioma growth, either in fixed tissue sections or living animals. Remarkable advantages are the use of immunocompetent animals and the simplified imaging method without the need of immunohistochemical procedures.

Association between brain structure and phenotypic characteristics in pedophilia.

PubMed

Poeppl, Timm B; Nitschke, Joachim; Santtila, Pekka; Schecklmann, Martin; Langguth, Berthold; Greenlee, Mark W; Osterheider, Michael; Mokros, Andreas

2013-05-01

Studies applying structural neuroimaging to pedophiles are scarce and have shown conflicting results. Although first findings suggested reduced volume of the amygdala, pronounced gray matter decreases in frontal regions were observed in another group of pedophilic offenders. When compared to non-sexual offenders instead of community controls, pedophiles revealed deficiencies in white matter only. The present study sought to test the hypotheses of structurally compromised prefrontal and limbic networks and whether structural brain abnormalities are related to phenotypic characteristics in pedophiles. We compared gray matter volume of male pedophilic offenders and non-sexual offenders from high-security forensic hospitals using voxel-based morphometry in cross-sectional and correlational whole-brain analyses. The significance threshold was set to p < .05, corrected for multiple comparisons. Compared to controls, pedophiles exhibited a volume reduction of the right amygdala (small volume corrected). Within the pedophilic group, pedosexual interest and sexual recidivism were correlated with gray matter decrease in the left dorsolateral prefrontal cortex (r = -.64) and insular cortex (r = -.45). Lower age of victims was strongly associated with gray matter reductions in the orbitofrontal cortex (r = .98) and angular gyri bilaterally (r = .70 and r = .93). Our findings of specifically impaired neural networks being related to certain phenotypic characteristics might account for the heterogeneous results in previous neuroimaging studies of pedophilia. The neuroanatomical abnormalities in pedophilia seem to be of a dimensional rather than a categorical nature, supporting the notion of a multifaceted disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Magnetic resonance lactate and lipid signals in rat brain after middle cerebral artery occlusion model

PubMed Central

Harada, Kuniaki; Honmou, Osamu; Liu, He; Bando, Michio; Houkin, Kiyohiro; Kocsis, Jeffery D.

2008-01-01

Proton magnetic resonance spectroscopy (1-H MRS) has revealed changes of metabolites in acute cerebral infarction. Although the drastic changes of lactate and N-acetyl-aspartate have been reported to be useful indicators of the ischemic damage in both humans and experimental animals, lipid signals are also detected by the short echo time sequence 1–5 days after ischemia. The objective of this study was to find a novel technique to isolate lactate signals from lipid signals in the ischemic brain. First, MRS was used to study the lipid and lactate components of a spherical phantom in vitro, and parameters were established to separate these components in vitro. Then, MR measurements were obtained from the brains of middle cerebral artery occlusion rats. All MR measurements were performed using a 7-T (300 MHz), 18.3-cm-bore superconducting magnet (Oxford Magnet Technologies) interfaced to a Unity INOVA Imaging System (Varian Technologies). T2-weighted images were obtained from a 1.0-mm-thick coronal section using a 3-cm field of view. It is well known that lipid has a shorter and lactate a longer T2 relaxation time. These distinct magnetic characteristics allowed us to separate the lactate signal from the lipid signal. Thus, adjustment of the echo time is essential to analyze the metabolites in acute cerebral infarction, which may be useful in both the clinic and laboratory. PMID:17196558

Live imaging of mitosis in the developing mouse embryonic cortex.

PubMed

Pilaz, Louis-Jan; Silver, Debra L

2014-06-04

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

Structural changes in socio-affective networks: Multi-modal MRI findings in long-term meditation practitioners.

PubMed

Engen, Haakon G; Bernhardt, Boris C; Skottnik, Leon; Ricard, Matthieu; Singer, Tania

2017-08-31

Our goal was to assess the effects of long-term mental training in socio-affective skills on structural brain networks. We studied a group of long-term meditation practitioners (LTMs) who have focused on cultivating socio-affective skills using loving-kindness and compassion meditation for an average of 40k h, comparing these to meditation-naïve controls. To maximize homogeneity of prior practice, LTMs were included only if they had undergone extensive full-time meditation retreats in the same center. MRI-based cortical thickness analysis revealed increased thickness in the LTM cohort relative to meditation-native controls in fronto-insular cortices. To identify functional networks relevant for the generation of socio-affective states, structural imaging analysis were complemented by fMRI analysis in LTMs, showing amplitude increases during a loving-kindness meditation session relative to non-meditative rest in multiple prefrontal and insular regions bilaterally. Importantly, functional findings partially overlapped with regions of cortical thickness increases in the left ventrolateral prefrontal cortex and anterior insula, suggesting that these regions may play a central role in the generation of emotional states relevant for the meditative practice. Our multi-modal MRI approach revealed structural changes in LTMs who have cultivated loving-kindness and compassion for a significant period of their life in functional networks activated by these practices. These preliminary cross-sectional findings motivate future longitudinal work studying brain plasticity following the regular practice of skills aiming at enhancing human altruism and prosocial motivation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.

PubMed

Peters, James H; Gallaher, Zachary R; Ryu, Vitaly; Czaja, Krzysztof

2013-10-15

Vagotomy, a severing of the peripheral axons of the vagus nerve, has been extensively utilized to determine the role of vagal afferents in viscerosensory signaling. Vagotomy is also an unavoidable component of some bariatric surgeries. Although it is known that peripheral axons of the vagus nerve degenerate and then regenerate to a limited extent following vagotomy, very little is known about the response of central vagal afferents in the dorsal vagal complex to this type of damage. We tested the hypothesis that vagotomy results in the transient withdrawal of central vagal afferent terminals from their primary central target, the nucleus of the solitary tract (NTS). Sprague-Dawley rats underwent bilateral subdiaphragmatic vagotomy and were sacrificed 10, 30, or 60 days later. Plastic changes in vagal afferent fibers and synapses were investigated at the morphological and functional levels by using a combination of an anterograde tracer, synapse-specific markers, and patch-clamp electrophysiology in horizontal brain sections. Morphological data revealed that numbers of vagal afferent fibers and synapses in the NTS were significantly reduced 10 days following vagotomy and were restored to control levels by 30 days and 60 days, respectively. Electrophysiology revealed transient decreases in spontaneous glutamate release, glutamate release probability, and the number of primary afferent inputs. Our results demonstrate that subdiaphragmatic vagotomy triggers transient withdrawal and remodeling of central vagal afferent terminals in the NTS. The observed vagotomy-induced plasticity within this key feeding center of the brain may be partially responsible for the response of bariatric patients following gastric bypass surgery. Copyright © 2013 Wiley Periodicals, Inc.

The Etiology of Cirrhosis is a Strong Determinant of Brain Reserve: A Multi-modal MR Imaging Study

PubMed Central

Ahluwalia, Vishwadeep; Wade, James B; Moeller, F Gerard; White, Melanie B; Unser, Ariel B; Gavis, Edith A; Sterling, Richard K; Stravitz, R Todd; Sanyal, Arun J; Siddiqui, Mohammad S; Puri, Puneet; Luketic, Velimir; Heuman, Douglas M; Fuchs, Michael; Matherly, Scott; Bajaj, Jasmohan S

2015-01-01

Background Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease severity and increase the patients’ vulnerability towards further deterioration. Aim To analyze brain reserve in abstinent alcoholic (Alc) compared to non-alcoholic (Nalc) cirrhosis patients in the context of hepatic encephalopathy (HE) and evaluate relative change in brain reserve between groups over time and before/after elective TIPS placement. Methods Cross-sectional study 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests followed by magnetic resonance (MR) imaging including 1-H MR Spectroscopy (MRS), Diffusion tensor (DTI) and T1-weighted imaging. Prospective study MRS on subset of 10 patients before/after TIPS placement. Another subset of 26 patients underwent MRS at least one year apart. Results Cross-sectional study Alc patients were worse on cognitive tests than Nalc. MR results suggest a greater effect of hyperammonemia, brain edema and significantly higher cortical damage in Alc as compared to Nalc patients. Effect of HE status on cognitive tests and brain reserve was more marked in Nalc than in Alc group. TIPS study Nalc patients showed a greater adverse relative change after TIPS compared to Alc group. 1-year follow-up Both groups remained stable between the two visits. However, Alc patients continued to show poor brain reserve than Nalc over time. Conclusions Patients with alcoholic cirrhosis, despite abstinence, have a poor brain reserve while, non-alcoholic cirrhosis patients have a greater potential for brain reserve deterioration after HE and TIPS. Information regarding the brain reserve in cirrhosis could assist medical teams to refine their communication and monitoring strategies for different etiologies. PMID:25939692

Brain stem sites mediating specific and non-specific temperature effects on thermoregulation in the pekin duck.

PubMed Central

Martin, R; Simon, E; Simon-Oppermann, C

1981-01-01

1. Thermodes were chronically implanted into various levels of the brain stem of sixteen Pekin ducks. The effects of local thermal stimulation on metabolic heat production, core temperature, peripheral skin temperature and respiratory frequency were investigated. 2. Four areas of thermode positions were determined according to the responses observed and were histologically identified at the end of the investigation. 3. Thermal stimulation of the lower mid-brain/upper pontine brain stem (Pos. III) elicited an increase in metabolic heat production, cutaneous vasoconstriction and rises in core temperature in response to cooling at thermoneutral and cold ambient conditions and, further, inhibition of panting by cooling and activation of panting by heating at warm ambient conditions. The metabolic response to cooling this brain stem section amounted to -0.1 W/kg. degrees C as compared with -7 W/kg. degrees C in response to total body cooling. 4. Cooling of the anterior and middle hypothalamus (Pos. II) caused vasodilatation in the skin and did not elicit shivering. The resulting drop in core temperature at a given degree of cooling was greater than the rise in core temperature in response to equivalent cooling of the lower mid-brain/upper pontine brain stem. 5. Cooling of the preoptic forebrain (Pos. I) and of the myelencephalon (Pos. IV) did not elicit thermoregulatory reactions. 6. It is concluded that the duck's brain stem contains thermoreceptive structures in the lower mid-brain/upper pontine section. However, the brain stem as a whole appears to contribute little to cold defence during general hypothermia because of the inhibitory effects originating in the anterior and middle hypothalamus. Cold defence in the duck, which is comparable in strength to that in mammals, has to rely on extracerebral thermosensory structures. PMID:7310688

76 FR 55400 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

...: Integrative, Functional and Cognitive Neuroscience Integrated Review Group; Auditory System Study Section... Neuroscience Integrated Review Group; Neurotoxicology and Alcohol Study Section. Date: October 13, 2011. Time... Disorders and Clinical Neuroscience Integrated Review Group; Developmental Brain Disorders Study Section...

Brain oxytocin: a key regulator of emotional and social behaviours in both females and males.

PubMed

Neumann, I D

2008-06-01

In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.

Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations.

PubMed

Beinfeld, Margery C; Blum, Alissa; Vishnuvardhan, Daesety; Fanous, Sanya; Marchand, James E

2005-11-18

Prohormone convertase 2 is widely co-localized with cholecystokinin in rodent brain. To examine its role in cholecystokinin processing, cholecystokinin levels were measured in dissected brain regions from prohormone convertase 2 knock-out mice. Cholecystokinin levels were lower in hippocampus, septum, thalamus, mesencephalon, and pons in knock-out mice than wild-type mice. In cerebral cortex, cortex-related structures and olfactory bulb, cholecystokinin levels were higher than wild type. Female mice were more affected by the loss of prohormone convertase 2 than male mice. The decrease in cholecystokinin levels in these brain regions shows that prohormone convertase 2 is important for cholecystokinin processing. Quantitative polymerase chain reaction measurements were performed to examine the relationship between peptide levels and cholecystokinin and enzyme expression. They revealed that cholecystokinin and prohormone convertase 1 mRNA levels in cerebral cortex and olfactory bulb were actually lower in knock-out than wild type, whereas their expression in other brain regions of knock-out mouse brain was the same as wild type. Female mice frequently had higher expression of cholecystokinin and prohormone convertase 1, 2, and 5 mRNA than male mice. The loss of prohormone convertase 2 alters CCK processing in specific brain regions. This loss also appears to trigger compensatory mechanisms in cerebral cortex and olfactory bulb that produce elevated levels of cholecystokinin but do not involve increased expression of cholecystokinin, prohormone convertase 1 or 5 mRNA.