The study of hominin brain evolution relies mostly on evaluation of the endocranial morphology of fossil skulls. However, only some general features of external brain morphology are evident from endocasts, and many anatomical details can be difficult or impossible to examine. In this study, we use geometric morphometric techniques to evaluate inter- and intraspecific differences in cerebral morphology in a sample of in vivo magnetic resonance imaging scans of chimpanzees and humans, with special emphasis on the study of asymmetric variation. Our study reveals that chimpanzee–human differences in cerebral morphology are mainly symmetric; by contrast, there is continuity in asymmetric variation between species, with humans showing an increased range of variation. Moreover, asymmetric variation does not appear to be the result of allometric scaling at intraspecific levels, whereas symmetric changes exhibit very slight allometric effects within each species. Our results emphasize two key properties of brain evolution in the hominine clade: first, evolution of chimpanzee and human brains (and probably their last common ancestor and related species) is not strongly morphologically constrained, thus making their brains highly evolvable and responsive to selective pressures; second, chimpanzee and, especially, human brains show high levels of fluctuating asymmetry indicative of pronounced developmental plasticity. We infer that these two characteristics can have a role in human cognitive evolution.
Gomez-Robles, Aida; Hopkins, William D.; Sherwood, Chet C.
The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high
W. F. C. Baare; H. E. Hulshoff-Poll; Dorret I. Boomsma; Daniëlle Posthuma; Geus de E. J. C; H. G. Snack; Haren van N. E. M; Oel van C. J; René S. Kahn
Dehydration can affect brain structure which has important implications for human health. In this study, we measured regional changes in brain structure following acute dehydration. Healthy volunteers received a structural MRI scan before and after an intensive 90-min thermal-exercise dehydration protocol. We used two techniques to determine changes in brain structure: a manual point counting technique using MEASURE, and a fully automated voxelwise analysis using SIENA. After the exercise regime, participants lost (2.2% +/- 0.5%) of their body mass. Using SIENA, we detected expansion of the ventricular system with the largest change occurring in the left lateral ventricle (P = 0.001 corrected for multiple comparisons) but no change in total brain volume (P = 0.13). Using manual point counting, we could not detect any change in ventricular or brain volume, but there was a significant correlation between loss in body mass and third ventricular volume increase (r = 0.79, P = 0.03). These results show ventricular expansion occurs following acute dehydration, and suggest that automated longitudinal voxelwise analysis methods such as SIENA are more sensitive to regional changes in brain volume over time compared with a manual point counting technique. PMID:18064587
Kempton, Matthew J; Ettinger, Ulrich; Schmechtig, Anne; Winter, Edward M; Smith, Luke; McMorris, Terry; Wilkinson, Iain D; Williams, Steven C R; Smith, Marcus S
Stem homographs are pairs of words with the same orthographic description of their stem but which are semantically and morphologically unrelated (e.g. in Spanish: rata/rato (rat/moment)). In priming tasks, stem homographs produce inhibition, unlike morphologically related words (loca/loco (madwoman/madman)) which produce facilitation. An event-related potentials study was conducted to compare morphological and stem homographic priming effects. The results show a similar attenuation of the N400 component at the 350-500 ms temporal window for the two conditions. In contrast, a broad negativity occurs only for stem homographs at the 500-600 ms window. This late negativity is interpreted as the consequence of an inhibitory effect for stem homographs that delays the stage of meaning integration. PMID:11803121
Barber, Horacio; Domínguez, Alberto; de Vega, Manuel
The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.
Budday, Silvia; Raybaud, Charles; Kuhl, Ellen
The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. PMID:25008163
Budday, Silvia; Raybaud, Charles; Kuhl, Ellen
Alcohol use disorders (AUD) and chronic cigarette smoking are common among individuals with human immunodeficiency virus infection (HIV). Concurrent AUD in HIV is related to greater abnormalities in brain morphology and neurocognition than either condition alone. However, the potential influence of chronic smoking on brain morphology and neurocognition in those concurrently afflicted with AUD and HIV has not been examined. The goal of this retrospective analysis was to determine if chronic smoking affected neurocognition and brain morphology in a subsample of HIV-positive non–treatment-seeking heavy drinking participants (HD+) from our earlier work. Regional volumetric and neurocognitive comparisons were made among age-equivalent smoking HD+(n = 17), nonsmoking HD+(n = 27), and nonsmoking HIV-negative light drinking controls (n = 27) obtained from our original larger sample. Comprehensive neuropsychological assessment evaluated multiple neurocognitive domains of functioning and for potential psychiatric comorbidities. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and sulcal and ventricular cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance images. The main findings were (1) smoking HD+ performed significantly worse than nonsmoking HD+ on measures of auditory-verbal (AV) learning, AV memory, and cognitive efficiency; (2) relative to controls, smoking HD+ demonstrated significantly lower neocortical GM volumes in all lobes except the occipital lobe, while nonsmoking HD+ showed only lower frontal GM volume compared with controls; (3) in the HD+ group, regional brain volumes and neurocognition were not influenced by viremia, highly active antiretroviral treatment, or Center for Disease Control symptom status, and no interactions were apparent with these variables or smoking status. Overall, the findings suggested that the direct and/or indirect effects of chronic cigarette smoking created an additional burden on the integrity of brain neurobiology and neurocognition in this cohort of HIV-positive heavy drinkers.
Durazzo, Timothy C.; Rothlind, Johannes C.; Cardenas, Valerie A.; Studholme, Colin; Weiner, Michael W.; Meyerhoff, Dieter J.
Alcohol use disorders (AUD) and chronic cigarette smoking are common among individuals with human immunodeficiency virus infection (HIV). Concurrent AUD in HIV is related to greater abnormalities in brain morphology and neurocognition than either condition alone. However, the potential influence of chronic smoking on brain morphology and neurocognition in those concurrently afflicted with AUD and HIV has not been examined. The goal of this retrospective analysis was to determine if chronic smoking affected neurocognition and brain morphology in a subsample of HIV-positive non-treatment-seeking heavy drinking participants (HD+) from our earlier work. Regional volumetric and neurocognitive comparisons were made among age-equivalent smoking HD+(n=17), nonsmoking HD+ (n=27), and nonsmoking HIV-negative light drinking controls (n=27) obtained from our original larger sample. Comprehensive neuropsychological assessment evaluated multiple neurocognitive domains of functioning and for potential psychiatric comorbidities. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and sulcal and ventricular cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance images. The main findings were (1) smoking HD+ performed significantly worse than nonsmoking HD+ on measures of auditory-verbal (AV) learning, AV memory, and cognitive efficiency; (2) relative to controls, smoking HD+ demonstrated significantly lower neocortical GM volumes in all lobes except the occipital lobe, while nonsmoking HD+ showed only lower frontal GM volume compared with controls; (3) in the HD+ group, regional brain volumes and neurocognition were not influenced by viremia, highly active antiretroviral treatment, or Center for Disease Control symptom status, and no interactions were apparent with these variables or smoking status. Overall, the findings suggested that the direct and/or indirect effects of chronic cigarette smoking created an additional burden on the integrity of brain neurobiology and neurocognition in this cohort of HIV-positive heavy drinkers. PMID:17923369
Durazzo, Timothy C; Rothlind, Johannes C; Cardenas, Valerie A; Studholme, Colin; Weiner, Michael W; Meyerhoff, Dieter J
Although the neurological basis of dyslexia has long been assumed, little direct evidence documents a relation between deviations in brain morphology and behavioral correlates of dyslexia. This article reviews two sources of evidence. Results of CT\\/MRI studies suggest that in the brains of dyslexics there is an increased incidence of symmetry in the region of the planum temporale and parietooccipital
George W. Hynd; Margaret Semrud-Clikeman
Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls; ii) is associated with patterns of cannabis use; and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among samples that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small sample sizes, heterogeneity across studies in sample characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research. PMID:23829361
Lorenzetti, Valentina; Solowij, Nadia; Fornito, Alex; Lubman, Dan Ian; Yucel, Murat
Although the correlations are modest (? r = 0.35), brain size as determined by magnetic resonance imaging has been positively related to measures of psychometric intelligence. Three studies dealing with brain size?IQ relationships are presented in patients who have suffered traumatic brain injury (TBI). Study 1 was an examination of whether the brain size?IQ relationship was proportionally maintained in response
Erin D. Bigler
We investigated neural distinctions between inflectional and derivational morphology and their interaction with lexical frequency using the mismatch negativity (MMN), an established neurophysiological index of experience-dependent linguistic memory traces and automatic syntactic processing. We presented our electroencephalography (EEG) study participants with derived and inflected words of variable lexical frequencies against their monomorphemic base forms in a passive oddball paradigm, along with acoustically matched pseudowords. Sensor space and distributed source modelling results showed that at 100-150 msec after the suffix onset, derived words elicited larger responses than inflected words. Furthermore, real derived words showed advantage over pseudo-derivations and frequent derivations elicited larger activation than less frequent ones. This pattern of results is fully in line with previous research that explained lexical MMN enhancement by an activation of strongly connected word-specific long-term memory circuits, and thus suggests stronger lexicalisation for frequently used complex words. At the same time, a strikingly different pattern was found for inflectional forms: higher response amplitude for pseudo-inflections than for real inflected words, with no clear frequency effects. This is fully in line with previous MMN results on combinatorial processing of (morpho)syntactic stimuli: higher response to ungrammatical morpheme strings than grammatical ones, which does not depend on the string's surface frequency. This pattern suggests that, for inflectional forms, combinatorial processing route dominates over whole-form storage and access. In sum, our results suggest that derivations are more likely to form unitary representations than inflections which are likely to be processed combinatorially, and imply at least partially distinct brain mechanisms for the processing and representation of these two types of morphology. These dynamic mechanisms, underpinned by perisylvian networks, are activated rapidly, at 100-150 msec after the information arrives at the input, and in a largely automatic fashion, possibly providing neural basis for the first-pass morphological processing of spoken words. PMID:24075689
Leminen, Alina; Leminen, Miika; Kujala, Teija; Shtyrov, Yury
Magnetic susceptibility varies among brain structures and provides insights into the chemical and molecular composition of brain tissues. However, the determination of an arbitrary susceptibility distribution from the measured MR signal phase is a challenging, ill-conditioned inverse problem. Although a previous method named calculation of susceptibility through multiple orientation sampling (COSMOS) has solved this inverse problem both theoretically and experimentally using multiple angle acquisitions, it is often impractical to carry out on human subjects. Recently, the feasibility of calculating the brain susceptibility distribution from a single-angle acquisition was demonstrated using morphology enabled dipole inversion (MEDI). In this study, we further improved the original MEDI method by sparsifying the edges in the quantitative susceptibility map that do not have a corresponding edge in the magnitude image. Quantitative susceptibility maps generated by the improved MEDI were compared qualitatively and quantitatively with those generated by calculation of susceptibility through multiple orientation sampling. The results show a high degree of agreement between MEDI and calculation of susceptibility through multiple orientation sampling, and the practicality of MEDI allows many potential clinical applications. PMID:21465541
Liu, Tian; Liu, Jing; de Rochefort, Ludovic; Spincemaille, Pascal; Khalidov, Ildar; Ledoux, James Robert; Wang, Yi
Background: Various studies have shown that a close physical and functional relationship exists between astrocytes and microglia during development. The maturation of astrocytes can be followed by their specific expression of glial fibrillary acidic protein (GFAP). Although there have been several reports on the expression of GFAP in the developing brain, these are mainly descriptive and have not defined clearly
Payam Rezaie; Norbert Ulfig; David Male
Studies of isolated craniosynostosis have shown biomechanical and biochemical influences on the craniofacial phenotype, resulting from both genetic and epigenetic factors. Much less attention has been directed toward the morphology of the brain, despite the interactive nature of the developing skull and developing brain. The aim of this study is to define the morphology of the brain in nonsyndromic unilateral coronal synostosis (UCS) in order to form more complete hypotheses about the cause of craniosynostosis. Landmark coordinate data were collected from 3D magnetic resonance image reconstructions of the brain in a sample of UCS patients and an age-matched morphologically normal cohort. These data were analyzed using Euclidean distance matrix analysis. The results of our study demonstrate that despite the basic similarity of overall shape of the brain and skull in UCS, the effects of craniosynostosis on the brain are not localized to structures immediately adjacent to the fused suture or to the endocranial surface of the skull. Rather, alterations are observed throughout the volume of the brain, with subcortical structures altered in conjunction with cortical changes. These results indicate that the morphological correlates are different for brain and skull and suggest that there is a large degree of independence in the developmental trajectories of the brain and skull. PMID:15977220
Aldridge, Kristina; Kane, Alex A; Marsh, Jeffrey L; Panchal, Jayesh; Boyadjiev, Simeon A; Yan, Peng; Govier, Daniel; Ahmad, Warda; Richtsmeier, Joan T
The activity of lactate dehydrogenase (LDH) and its isozyme composition were analyzed in 41 unaffected human fetal brains of 18–42 weeks of gestation. Regional differences either in the levels of activity or in the patterns of development were observed. Throughout the 24-week period, the highest LDH activity was found in the spinal cord and the brain stem. Activity rises with
A. Chabás; P. Briones; J. Sabater
The morphology of healthy and pathological human brain tissue, as well as the brain structural organization of various animal models has been imaged in-vitro using ultrahigh resolution optical coherence tomography (UHR OCT). Micrometer-scale OCT resolution (< 2 ?m axial resolution) was achieved at different central wavelengths by interfacing three state-of-the-art broad bandwidth light sources (Ti:Al2O3, ?c = 790 nm, ?? = 260 nm and Pout = 50 mW; PCF based laser, ?c = 1150 nm, ?? = 350 nm and Pout = 2 W; Fiber laser based light source, ?c = 1350 nm, ?? = 470 nm and Pout = 4 mW) to a modular free-space OCT system, utilizing a dynamic focusing and designed for optimal performance in the appropriate wavelength regions. Images acquired from a fixed honeybee brain demonstrated the ability of UHR OCT to image the globular structure of the brain, some fine morphological details such as the nerve fiber bundles connecting the medulla (visual center) to the honeybee eyes, and the interfaces between different tissue layers in the medulla. Tomograms of various human neuropathologies demonstrated the feasibility of UHR OCT to visualize morphological details such as small (~20 ?m) calcifications typical for fibrous meningioma, and enlarged nuclei of cancer cells (~10-15 ?m) characteristic for many other neuropathologies. In addition UHR OCT was used to image cellular morphology in living ganglion cells.
Bizheva, Kostadinka K.; Unterhuber, Angelika; Hermann, Boris; Povazay, Boris; Sattmann, Harald; Mei, Michael; Holzwarth, Ronald; Preusser, Matthias; Reitsamer, Herbert; Seefeldt, Michael; Menzel, Ralf; Budka, Herbert; Fercher, Adolf F.; Drexler, Wolfgang
Malate dehydrogenase (MDH) activity was analyzed in the CNS of 43 unaffected human fetuses aged 18–42 weeks of gestation. Regional differences in the levels of activity were observed at every age. MDH activity rises during this period in all areas, but the increase occurs prior to the 30th week in brain stem and spinal cord, and later in the other
A. Chabás; P. Briones; J. Sabater
Given the current emphasis on research into human neurodegenerative diseases, an effective computing approach for the analysis of complex brain morphological changes would represent a significant technological innovation. The availability of mouse models of such disorders provides an experimental system to test novel approaches to brain image analysis. Here we utilize a mouse model of a neurodegenerative disorder to model changes to cerebellar morphology during the postnatal period, and have applied the GeoEntropy algorithm to measure the complexity of morphological changes.
El-Fiqi, Heba Z.; Pham, Tuan D.; Hattori, Haroldo T.; Crane, Denis I.
Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. © 2014 Wiley Periodicals, Inc. PMID:24788405
Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T
"Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…
Posner, Michael I.; Rothbart, Mary K.
Obstructive sleep apnea (OSA) is accompanied by neurocognitive impairment, likely mediated by injury to various brain regions. We evaluated brain morphological changes in patients with OSA and their relationship to neuropsychological and oximetric data. Sixteen patients affected by moderate-severe OSA (age: 55.8±6.7years, 13 males) and fourteen control subjects (age: 57.6±5.1years, 9 males) underwent 3.0 Tesla brain magnetic resonance imaging (MRI)
Federico Torelli; Nicola Moscufo; Girolamo Garreffa; Fabio Placidi; Andrea Romigi; Silvana Zannino; Marco Bozzali; Fabrizio Fasano; Giovanni Giulietti; Ina Djonlagic; Atul Malhotra; Maria Grazia Marciani; Charles R. G. Guttmann
In the last three decades, much emphasis has been placed on neural oscillations in vitro, in vivo, as well as in the human brain. These brain oscillations have been studied extensively in the resting electroencephalogram (EEG), as well as in the underlying evoked oscillations that make up the event-related potentials (ERPs). There are several approaches to elucidate the possible mechanisms
Henri Begleiter; Bernice Porjesz
Chronic pain can be understood not only as an altered functional state, but also as a consequence of neuronal plasticity. Here we use in vivo structural MRI to compare global, local, and architectural changes in gray matter properties in patients suffering from chronic back pain (CBP), complex regional pain syndrome (CRPS) and knee osteoarthritis (OA), relative to healthy controls. We find that different chronic pain types exhibit unique anatomical ‘brain signatures’. Only the CBP group showed altered whole-brain gray matter volume, while regional gray matter density was distinct for each group. Voxel-wise comparison of gray matter density showed that the impact on the extent of chronicity of pain was localized to a common set of regions across all conditions. When gray matter density was examined for large regions approximating Brodmann areas, it exhibited unique large-scale distributed networks for each group. We derived a barcode, summarized by a single index of within-subject co-variation of gray matter density, which enabled classification of individual brains to their conditions with high accuracy. This index also enabled calculating time constants and asymptotic amplitudes for an exponential increase in brain re-organization with pain chronicity, and showed that brain reorganization with pain chronicity was 6 times slower and twice as large in CBP in comparison to CRPS. The results show an exuberance of brain anatomical reorganization peculiar to each condition and as such reflecting the unique maladaptive physiology of different types of chronic pain.
Baliki, Marwan N.; Schnitzer, Thomas J.; Bauer, William R.; Apkarian, A. Vania
Although the mineral magnetite (Fe3O4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite-maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and greater than 100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high-field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields. Images
Kirschvink, J L; Kobayashi-Kirschvink, A; Woodford, B J
Although the mineral magnetite (Fe_3O_4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite-maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and >100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high-field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields.
Kirschvink, Joseph L.; Kobayashi-Kirschvink, Atsuko; Woodford, Barbara J.
Methods for the analysis of brain morphology, including voxel-based morphology and surface-based morphometries, have been used to detect associations between brain structure and covariates of interest, such as diagnosis, severity of disease, age, IQ, and genotype. The statistical analysis of morphometric measures usually involves two statistical procedures: 1) invoking a statistical model at each voxel (or point) on the surface of the brain or brain subregion, followed by mapping test statistics (e.g., t test) or their associated p values at each of those voxels; 2) correction for the multiple statistical tests conducted across all voxels on the surface of the brain region under investigation. We propose the use of new statistical methods for each of these procedures. We first use a heteroscedastic linear model to test the associations between the morphological measures at each voxel on the surface of the specified subregion (e.g., cortical or subcortical surfaces) and the covariates of interest. Moreover, we develop a robust test procedure that is based on a resampling method, called wild bootstrapping. This procedure assesses the statistical significance of the associations between a measure of given brain structure and the covariates of interest. The value of this robust test procedure lies in its computationally simplicity and in its applicability to a wide range of imaging data, including data from both anatomical and functional magnetic resonance imaging (fMRI). Simulation studies demonstrate that this robust test procedure can accurately control the family-wise error rate. We demonstrate the application of this robust test procedure to the detection of statistically significant differences in the morphology of the hippocampus over time across gender groups in a large sample of healthy subjects.
Ibrahim, Joseph G.; Tang, Niansheng; Rowe, Daniel B.; Hao, Xuejun; Bansal, Ravi; Peterson, Bradley S.
Human microvascular endothelial cells were isolated from children's brain and examined for their morphological characteristics and upregulation of cell adhesion molecules in response to TNF?. Our human brain microvascular endothelial cells (HBMEC) were positive for factor VIII-Rag, carbonic anhydrase IV, Ulex Europeus Agglutinin I, took up fluorescently labeled acetylated low density lipoprotein and expressed gamma glutamyl transpeptidase, demonstrating their brain
Monique F Stins; Floyd Gilles; Kwang Sik Kim
Background Human skull and brain morphology are strongly influenced by genetic factors, and skull size and shape vary worldwide. However, the relationship between specific brain morphology and genetically-determined ancestry is largely unknown. Methods We used two independent data sets to characterize variation in skull and brain morphology among individuals of European ancestry. The first data set is a historical sample of 1,170 male skulls with 37 shape measurements drawn from 27 European populations. The second data set includes 626 North American individuals of European ancestry participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with magnetic resonance imaging, height and weight, neurological diagnosis, and genome-wide single nucleotide polymorphism (SNP) data. Results We found that both skull and brain morphological variation exhibit a population-genetic fingerprint among individuals of European ancestry. This fingerprint shows a Northwest to Southeast gradient, is independent of body size, and involves frontotemporal cortical regions. Conclusion Our findings are consistent with prior evidence for gene flow in Europe due to historical population movements and indicate that genetic background should be considered in studies seeking to identify genes involved in human cortical development and neuropsychiatric disease.
Bakken, Trygve E.; Dale, Anders M.; Schork, Nicholas J.
Many cellular constituents in the human brain permanently exit from the cell cycle during pre- or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether >100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size.
Houston, Isaac; Peter, Cyril J; Mitchell, Amanda; Straubhaar, Juerg; Rogaev, Evgeny; Akbarian, Schahram
Summary Understanding human-specific patterns of brain gene expression and regulation can provide key insights into human brain evolution and speciation. Here, we use next generation sequencing, and Illumina and Affymetrix microarray platforms, to compare the transcriptome of human, chimpanzee, and macaque telencephalon. Our analysis reveals a predominance of genes differentially expressed within human frontal lobe and a striking increase in transcriptional complexity specific to the human lineage in the frontal lobe. In contrast, caudate nucleus gene expression is highly conserved. We also identify gene co-expression signatures related to either neuronal processes or neuropsychiatric diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes co-expressed with FOXP2, a gene important for language evolution. These data demonstrate that transcriptional networks have undergone evolutionary remodeling even within a given brain region, providing a new window through which to view the foundation of uniquely human cognitive capacities.
Konopka, Genevieve; Friedrich, Tara; Davis-Turak, Jeremy; Winden, Kellen; Oldham, Michael C.; Gao, Fuying; Chen, Leslie; Wang, Guang-Zhong; Luo, Rui; Preuss, Todd M.; Geschwind, Daniel H.
Humans, compared to other species, have exceptional capability for dissipation of heat from the entire skin surface. We can secrete more than two liters per hour of sweat, indefinitely. The corresponding potential for evaporative cooling is near a thousand watts, sufficient to compensate for the extreme high levels of heat production during exercise. Also, the blood vessels of our skin have exceptional capability to dilate and deliver heat to the body surface. These are our special adaptations for thermal stress. They allow prolonged heavy exercise with modest elevations in the temperature of the fluid that cools all the internal organs, not just the brain-arterial blood. The vascular architecture of the human head is radically different from that of animals that exhibit SBC. These species have special adaptations that reflect their dependence on respiratory evaporation, particularly the limitation imposed on capability to dispose of heat produced during exercise. The increase in blood temperature in an intense sprint would heat the well-perfused brain rapidly. But the heat exchange over the large surface area of contact between a venous plexus cooled by respiratory evaporation and the meshwork of arterial vessels in the carotid rete precools blood bound for the brain. Specialized cooling of the brain (SBC) has not been demonstrated by direct measurements in humans. Changes in tympanic temperature (Tty) are taken as evidence for SBC. This continues an unfortunate tradition of exaggeration of the significance of Tty. In the only direct measurements available, brain temperature was unaffected by fanning the face although Tty did fall. What may appear to be a remnant of the carotid rete heat exchanger in humans is the intimate association between a short segment of the internal carotid artery and the plexus of veins in the cavernous sinus. Fortunately, the brain need not rely for its cooling on countercurrent heat exchange across this small surface area of contact. In humans, SBC stands for skin: the body cooler--we use our entire skin surface for heat dissipation. PMID:8375613
Brengelmann, G L
While much work has been conducted regarding the neurogenesis response to traumatic brain injury (TBI) in rodents, it remains largely unknown whether neurogenesis in adult human brain also responds to TBI in a similar manner. Here, we performed immunocytochemistry on 11 brain specimens from patients with traumatic brain injury, who underwent surgical intervention. We found that expression of neural stem/progenitor cell (NSC) protein markers, including DCX, TUC4, PSA-NCAM, SOX2 and NeuroD, was increased in the perilesional cortex of human brain after TBI compared to that of normal brain. Confocal images showed that these NSC proteins were expressed in one single cell. We also found that proliferative markers were expressed in NSC protein-positive cells after TBI, and the number of proliferative NSCs was significantly increased after TBI. Our data suggest that TBI may also induce neurogenesis in human brain. PMID:21275797
Zheng, WeiMing; ZhuGe, Qichuan; Zhong, Ming; Chen, Gourong; Shao, Bei; Wang, Hong; Mao, XiaoOu; Xie, Lin; Jin, Kunlin
Social status impacts reproductive behavior in diverse vertebrate species, but little is known about how it affects brain morphology. We explore this in the naked mole-rat, a species with the most rigidly organized reproductive hierarchy among mammals. Naked mole-rats live in large, subterranean colonies where breeding is restricted to a single female and small number of males. All other members of the colony, known as subordinates, are reproductively suppressed. Subordinates can become breeders if removed from the colony and placed with an opposite sex partner, but in nature most individuals never attain reproductive status. We examined the brains of breeding and subordinate naked mole-rats of both sexes, including several regions linked to reproduction and shown to be sexually dimorphic in other mammals. Stereological analyses revealed that neural morphology depends on status, such that breeders, regardless of sex, had more cells than subordinates in the ventromedial nucleus of the hypothalamus and a larger volume of the bed nucleus of the stria terminalis, paraventricular nucleus, and medial amygdala. Several other brain regions examined were unaffected. Surprisingly, males and females did not differ on any measure. These findings provide evidence that a change in social status triggers considerable neural remodeling and indicate that status, rather than sex, has a predominant role in determining neural structure in this remarkably social mammal. PMID:17556547
Holmes, Melissa M; Rosen, Greta J; Jordan, Cynthia L; de Vries, Geert J; Goldman, Bruce D; Forger, Nancy G
Power Point slides that can be used during the sheep brain dissection laboratory to visually compare the sheep brain to the human brain structures with the goal to learn the anatomy of the human brain.
PhD Margarita P Bracamonte (Northland Community & Technical College Biology)
BACKGROUND AND PURPOSE: Quantifying changes in the human brain that occur as part of normal aging may help in the diagnosis of diseases that affect the elderly and that cause structural changes in the brain. We sought to assess diffusion changes that are inherently related to brain structure during aging. METHODS: MR scans were obtained from 11 healthy volunteers and
Terry Chun; Christopher G. Filippi; Robert D. Zimmerman; Aziz M. Ulug
Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences.
Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.
Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.
Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders.
Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P. (Rockefeller Univ., New York, NY (USA))
In development, timing is of the utmost importance, and the timing of developmental processes often changes as organisms evolve. In human evolution, developmental retardation, or neoteny, has been proposed as a possible mechanism that contributed to the rise of many human-specific features, including an increase in brain size and the emergence of human-specific cognitive traits. We analyzed mRNA expression in the prefrontal cortex of humans, chimpanzees, and rhesus macaques to determine whether human-specific neotenic changes are present at the gene expression level. We show that the brain transcriptome is dramatically remodeled during postnatal development and that developmental changes in the human brain are indeed delayed relative to other primates. This delay is not uniform across the human transcriptome but affects a specific subset of genes that play a potential role in neural development.
Somel, Mehmet; Franz, Henriette; Yan, Zheng; Lorenc, Anna; Guo, Song; Giger, Thomas; Kelso, Janet; Nickel, Birgit; Dannemann, Michael; Bahn, Sabine; Webster, Maree J.; Weickert, Cynthia S.; Lachmann, Michael; Paabo, Svante; Khaitovich, Philipp
Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also
The complex development of the human brain during infancy can only be understood by convergent structural, functional, and behavioral measurements. The evaluation of event-related potentials (ERPs) is the most effective current way to look at infant brain function. ERP paradigms can be used to examine the simple transmission of sensory information to the cortex and the discrimination of this information
Terence W. Picton; Margot J. Taylor
There is increasing evidence that genomic imprinting, a process by which certain genes are expressed in a parent-of-origin specific manner, can influence neurogenetic and psychiatric manifestations. While some data suggest possible imprinting effects of the X-chromosome on physical and cognitive characteristics in human, there is no compelling evidence that X-linked imprinting affects brain morphology. To address this issue, we investigated regional cortical volume, thickness and surface area in 27 healthy controls and 40 prepubescent girls with Turner syndrome (TS), a condition caused by the absence of one X-chromosome. Of the young girls with TS, 23 inherited their X-chromosome from their mother (Xm) and 17 from their father (Xp). Our results confirm the existence of significant differences in brain morphology between girls with TS and controls, and reveal the presence of a putative imprinting effect among the TS groups: girls with Xp demonstrated thicker cortex than those with Xm in the temporal regions bilaterally, while Xm individuals showed bilateral enlargement of gray matter volume in the superior frontal regions in comparison to Xp. These data suggest the existence of imprinting effects of the X-chromosome that influence both cortical thickness and volume during early brain development, and help to explain variability in cognitive and behavioral manifestations of TS with regard to the parental origin of the X-chromosome.
Lepage, Jean-Francois; Hong, David S.; Mazaika, Paul K.; Raman, Mira; Sheau, Kristen; Marzelli, Matthew J.; Hallmayer, Joachim; Reiss, Allan L.
The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored. PMID:24936682
Amunts, K; Hawrylycz, M J; Van Essen, D C; Van Horn, J D; Harel, N; Poline, J-B; De Martino, F; Bjaalie, J G; Dehaene-Lambertz, G; Dehaene, S; Valdes-Sosa, P; Thirion, B; Zilles, K; Hill, S L; Abrams, M B; Tass, P A; Vanduffel, W; Evans, A C; Eickhoff, S B
Studies utilizing human brain tissue examined the colocalozation of neurotransmitters using immunocytochemical and in vitro hybridization techniques. Results have shown the coexistance of somatostatin and neuropeptide Y in the hippocampus, and galanin and...
Although the mineral magnetite (Fe_3O_4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with
Joseph L. Kirschvink; Atsuko Kobayashi-Kirschvink; Barbara J. Woodford
Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm3, some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an ?3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species.
Falk, Dean; Hildebolt, Charles; Smith, Kirk; Morwood, M. J.; Sutikna, Thomas; Jatmiko; Saptomo, E. Wayhu; Imhof, Herwig; Seidler, Horst; Prior, Fred
It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density. Intervertebral core samples [n?=?96, 14 subjects, L1-L5 level, ages 35-85 (64?±?16 years), degeneration grade 1 (n?=?4), grade 2 (n?=?32), grade 3 (n?=?44), grade 4 (n?=?10), grade 5 (n?=?6)] that included subchondral bone, cartilage endplate, and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using µCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed. Contrary to the prevailing notion, vertebral endplate porosity increased between 50% and 130% and trabecular thickness decreased by between 20% and 50% with advancing disc degeneration (p?0.05). We also observed that nucleus cell density increased (R(2) ?=?0.33, p?0.05) and proteoglycan content decreased (R(2) ?=?0.47, p?0.05) as the endplate became more porous. Our data suggest that endplate sclerosis is not a fundamental factor contributing to disc degeneration. Rather, the opposite was observed in our samples, as the endplate became progressively more porous with age and degeneration. Since ischemic disc cell behavior is commonly associated with degenerative change, this may be related to other factors such as the quality of vertebral capillaries, as opposed to decreased permeability of intervening tissues. PMID:21812023
Rodriguez, Azucena G; Rodriguez-Soto, Ana E; Burghardt, Andrew J; Berven, Sigurd; Majumdar, Sharmila; Lotz, Jeffrey C
ABSTRACT The connection matrix of the human brain (the human “connectome”) represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.
Sporns, Olaf; Tononi, Giulio; Kotter, Rolf
Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants' current and future behavior. Indeed, the parent-infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust-likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain-from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic-midbrain-limbic-paralimbic-cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196
Swain, James E
The past two decades have witnessed tremendous advances in noninvasive and postmortem neuroscientific techniques, advances that have made it possible, for the first time, to compare in detail the organization of the human brain to that of other primates. Studies comparing humans to chimpanzees and other great apes reveal that human brain evolution was not merely a matter of enlargement, but involved changes at all levels of organization that have been examined. These include the cellular and laminar organization of cortical areas; the higher-order organization of the cortex, as reflected in the expansion of association cortex (in absolute terms, as well as relative to primary areas); the distribution of long-distance cortical connections; and hemispheric asymmetry. Additionally, genetic differences between humans and other primates have proven to be more extensive than previously thought, raising the possibility that human brain evolution involved significant modifications of neurophysiology and cerebral energy metabolism.
Preuss, Todd M.
In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brain regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. As the developing human brain is more mature at birth than the rat brain, the risk for microneuronal hypoplasia and consequent behavioral disorders may be highest at late stages of fetal development, in prematurely born and small-for-weight infants, and during the early stages of infant development. Recent technological advances in brain imaging techniques make it possible to test this hypothesis and to assess the possible relationship between the degree of retarded brain development and ensuing behavioral disorders. Images FIGURE 9. FIGURE 2. FIGURE 5. FIGURE 14. A FIGURE 14. B FIGURE 14. C
The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem
Sheila K. Singh; Cynthia Hawkins; Ian D. Clarke; Jeremy A. Squire; Jane Bayani; Takuichiro Hide; R. Mark Henkelman; Michael D. Cusimano; Peter B. Dirks
Background Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology In a large sample of healthy individuals (N?=?303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (?174?C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x?=?24, y?=??10, z?=??15; F(2,286)?=?8.54, puncorrected?=?0.0002; pAlphaSim-corrected?=?0.002; cluster size k?=?577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.
Recent advances in MRI technology have enabled precise measurements of correlated activity throughout the brain, leading to the first comprehensive descriptions of functional brain networks in humans. This article reviews the growing literature on the development of functional networks, from infancy through adolescence, as measured by resting state functional connectivity MRI. We note several limitations of traditional approaches to describing brain networks, and describe a powerful framework for analyzing networks, called graph theory. We argue that characterization of the development of brain systems (e.g. the default mode network) should be comprehensive, considering not only relationships within a given system, but also how these relationships are situated within wider network contexts. We note that, despite substantial reorganization of functional connectivity, several large-scale network properties appear to be preserved across development, suggesting that functional brain networks, even in children, are organized in manners similar to other complex systems.
Power, Jonathan D; Fair, Damien A; Schlaggar, Bradley L
This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.
Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)
The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. PMID:24695229
Miller, Jeremy A; Ding, Song-Lin; Sunkin, Susan M; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L; Royall, Joshua J; Aiona, Kaylynn; Arnold, James M; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Dolbeare, Tim A; Facer, Benjamin A C; Feng, David; Fliss, Tim P; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W; Gu, Guangyu; Howard, Robert E; Jochim, Jayson M; Kuan, Chihchau L; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D; Parry, Sheana E; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V; Shen, Elaine H; Sjoquist, Nathan; Slaughterbeck, Clifford R; Smith, Michael; Sodt, Andy J; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B; Geschwind, Daniel H; Glass, Ian A; Hawrylycz, Michael J; Hevner, Robert F; Huang, Hao; Jones, Allan R; Knowles, James A; Levitt, Pat; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G; Lein, Ed S
Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric\\u000a conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis.\\u000a However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect.\\u000a Thus, the objective of our study was
Brian M. Ross; Anna Moszczynska; Jan K. Blusztajn; Allan Sherwin; Andres Lozano; Stephen J. Kish
I give a brief description of the magnetic resonance spectroscopy (MRS) in the human brain examinations. MRS allows a noninvasive chemical analysis of the brain using a standard high field MR system. Nowadays, the dominant form of MR brain spectroscopy is proton spectroscopy. Two main techniques of MRS, which utilize the chemical shift of metabolites in the external magnetic field, are SVS (single voxel) and CSI (single slice). The major peaks in the spectrum of a normal brain include NAA, Cr, Cho and m-Ins, which are neuronal, energetic, membrane turnover and glial markers, respectively. In disease, two pathological metabolites can be found in the brain spectra: Lac, which is end product of anaerobic glycolysis and Lip, which is a marker of membrane breakdown, occurring in necrosis. The common way to analyze clinical spectra is to determine metabolite ratios, e.g. NAA/Cr, Cho/Cr, Cho/NAA. This analysis permits a safe and noninvasive examination of the brain tissue as each disease state has its own characteristic spectroscopic image. MRS is a valuable diagnostic tool in such clinical applications as detecting brain tumors and differentiating tumors from inflammatory and infectious processes. Proton MRS is also very helpful in diagnostic of ischemic lesions, Alzheimer's disease and hepatic encephalopathy. The MRS brain spectra should always be correlated with the Magnetic Resonance Imaging (MRI) results and alone cannot make neurological diagnosis.
Dopamine is an important regulator of cognition and behavior, but its precise influence on human brain processing remains unclear because of the lack of a reliable technique to study dopamine in the live human brain. In the recent years, a number of techniques have been developed to detect, map, and measure dopamine released during task performance. Most of these techniques are based on molecular imaging methods and have varying degrees of sensitivity. We developed a single-scan dynamic molecular imaging technique for the detection of dopamine released during task performance in the live human brain. This technique is extremely sensitive and has test–retest reliability. Using this technique, we detected dopamine released during the processing of a number of cognitive, behavioral, and emotional tasks. Since this technique acquires data that cannot be obtained using any other techniques, it extends the scope of neuroimaging research.
Badgaiyan, Rajendra D.
Albinism, in humans and many animal species, has a major impact on the visual system, leading to reduced acuity, lack of binocular function and nystagmus. In addition to the lack of a foveal pit, there is a disruption to the routing of the nerve fibers crossing at the optic chiasm, resulting in excessive crossing of fibers to the contralateral hemisphere. However, very little is known about the effect of this misrouting on the structure of the post-chiasmatic visual pathway, and the occipital lobes in particular. Whole-brain analyses of cortical thickness in a large cohort of subjects with albinism showed an increase in cortical thickness, relative to control subjects, particularly in posterior V1, corresponding to the foveal representation. Furthermore, mean cortical thickness across entire V1 was significantly greater in these subjects compared to controls and negatively correlated with visual acuity in albinism. Additionally, the group with albinism showed decreased gyrification in the left ventral occipital lobe. While the increase in cortical thickness in V1, also found in congenitally blind subjects, has been interpreted to reflect a lack of pruning, the decreased gyrification in the ventral extrastriate cortex may reflect the reduced input to the foveal regions of the ventral visual stream. PMID:23039995
Bridge, Holly; von dem Hagen, Elisabeth A H; Davies, George; Chambers, Claire; Gouws, Andre; Hoffmann, Michael; Morland, Antony B
A methodology has been described for reliable cultivation in vitro of dispersed fibroblastic cells obtained from normal human organs. The procedure has permitted establishment of stable cell lines from almost every sample taken, among which the following organs were represented: skin, spleen, amnion, lung, liver, bone marrow, brain, muscle, and heart. Equally good growth has been achieved with cells from embryonic or adult tissues. The methods previously developed whereby single cells plated in Petri dishes grow into isolated macroscopic colonies can successfully be applied to the plating of human fibroblastic stocks. Plating efficiencies in the neighborhood of 50 to 60 per cent are readily achieved with such strains. The resulting colonies can be picked and clonal stocks established. Fibroblastic morphology is maintained in the colonies arising from every single cell of such clonal stocks. All of the single cells from epithelioid clonal strains also maintain their integrity throughout repeated subculture. Since the difference between clonal stocks of these two types is always maintained whenever the respective single cells are plated in the same medium, regardless of the previous history of these stocks, it may be concluded that a true genetic difference exists in these cell lines. In addition to the morphological differences between epithelioid and fibroblastic cell strains, the latter have more demanding nutritional requirements for single cell growth. Thus, single cells of fibroblastic lines almost never produce colonies with high efficiency unless the growth medium which is sufficient for epithelioid cells is supplemented with embryo extract, or a cell feeder layer. Fibroblastic cells are also more resistant to tryptic digestion of the bond uniting the cells to glass surfaces. By use of differential media, growth of both fibroblastic and epithelioid cells, respectively, has been obtained, from dispersed single cells obtained by trypsinization of a specimen of human embryonic lung.
Puck, Theodore T.; Cieciura, Steven J.; Fisher, Harold W.
In Huntington's diseased human brain, it is in the caudate nucleus (CN) and globus pallidus (GP) of the basal ganglia where nerve cell death is seen most dramatically. The distribution of five gap junction proteins (connexins 26, 32, 40, 43 and 50) has been examined in these areas in normal and Huntington's diseased human brain using immunohistochemical techniques. There was no Cx50 expression observed and Cx40 was localized in the endothelial cells of blood vessels, with the Huntington's diseased brains having more numerous and smaller blood vessels than normal tissue. Cx26 and Cx32 revealed a similar distribution pattern to each other in both normal and diseased brains with little labelling in the CN but clear labelling in the GP. Cx43, expressed by astrocytes, was the most abundant connexin type of those studied. In both normal and diseased brains Cx43 in the GP was homogeneously distributed in the neuropil. In the CN, however, Cx43 density was both increased with Huntington's disease and became located in patches. Glial fibrillary acidic protein(GFAP) staining of astrocytes was also highly increased in the CN compared with normal brains. These labelling patterns indicate a reactive astrocytosis around degenerating neurons with an increased expression of astrocytic gap junctions. The enhanced coupling state between astrocytes, assuming the junctions are functional, could provide an increased spatial buffering capacity by the astrocytes in an attempt to maintain a proper environment for the neurons, helping promote neuronal survival in this neurodegenerative disorder. PMID:10873295
Vis, J C; Nicholson, L F; Faull, R L; Evans, W H; Severs, N J; Green, C R
Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticity-related morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders.
Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya
Intelligence can be defined as a general mental ability for reasoning, problem solving, and learning. Because of its general nature, intelligence integrates cognitive functions such as perception, attention, memory, language, or planning. On the basis of this definition, intelligence can be reliably measured by standardized tests with obtained scores predicting several broad social outcomes such as educational achievement, job performance, health, and longevity. A detailed understanding of the brain mechanisms underlying this general mental ability could provide significant individual and societal benefits. Structural and functional neuroimaging studies have generally supported a frontoparietal network relevant for intelligence. This same network has also been found to underlie cognitive functions related to perception, short-term memory storage, and language. The distributed nature of this network and its involvement in a wide range of cognitive functions fits well with the integrative nature of intelligence. A new key phase of research is beginning to investigate how functional networks relate to structural networks, with emphasis on how distributed brain areas communicate with each other.
Colom, Roberto; Karama, Sherif; Jung, Rex E.; Haier, Richard J.
Brain metastasis is a major cause of morbidity and mortality in patients with melanoma. The molecular changes that lead to brain metastasis remain poorly understood. In this study, we developed a model to study human melanoma brain metastasis and found that Stat3 activity was increased in human brain metastatic melanoma cells when compared with that in cutaneous melanoma cells. The
Tong-xin Xie; Feng-Ju Huang; Kenneth D. Aldape; Mingguang Liu; Jeffrey E. Gershenwald; Keping Xie; Raymond Sawaya; Suyun Huang
Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants' current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance
James E. Swain
The report reviews the pertinent literature and adds additional evidence indicating that the human brain may be able to tolerate head impact forces in the range of 300 to 400 g's without evidence of concussion or other detectable neurologic sequelae, prov...
J. J. Swearingen
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand gated ion channels which are widely distributed in the human brain. Multiple subtypes of these receptors exist, each with individual pharmacological and functional profiles. They mediate the effects of nicotine, a widely used drug of abuse, are involved in a number of physiological and behavioural processes and are additionally implicated
David Paterson; Agneta Nordberg
Despite many years of research on the neural correlates of consciousness (NCCs), it is still unclear how the detailed contents of consciousness are represented in the human brain. It is often assumed that specific con- tents of consciousness are encoded in dedicated core NCCs - one for each different aspect of conscious experi- ence. Now, the approach of multivariate decoding
Abstract During the last ten years there has been growing interest in the development of Brain Computer Interfaces (BCIs). The eld,has mainly been driven by the needs of completely paralyzed patients to communicate. With a few exceptions, most human BCIs are based on extracranial electroencephalography (EEG). However, reported bit rates are still low. One reason for this is the low
T. N. Lal; T. Hinterberger; G. Widman; N. J. Hill; W. Rosenstiel; C. E. Elger; N. Birbaum
During the last ten years there has been growing interest in the develop- ment of Brain Computer Interfaces (BCIs). The eld has mainly been driven by the needs of completely paralyzed patients to communicate. With a few exceptions, most human BCIs are based on extracranial elec- troencephalography (EEG). However, reported bit rates are still low. One reason for this is
Thomas Navin Lal; Thilo Hinterberger; Guido Widman; Michael Schröder; N. Jeremy Hill; Wolfgang Rosenstiel; Christian Erich Elger; Bernhard Schölkopf; Niels Birbaumer
Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references.
Testican is a putative extracellular heparan/ chondroitin sulfate proteoglycan of unknown function that is expressed in a variety of human tissues at widely different levels but is most abundant in the brain. In mice, testican mRNA has been detected only in brain and it is therefore likely to have an important function in the central nervous system. RNA blot analysis reveals the relative intensity of testican in various regions of the human brain. Levels of testican message are most pronounced in the thalamus, hippocampus, occipital lobe, nucleus accumbens, temporal lobe, and caudate nucleus, with somewhat lower levels in the cerebral cortex, medulla oblongata, frontal lobe, amygdala, putamen, spinal cord, substantia nigra, and cerebellum. In situ hybridization reveals the cellular distribution of the mRNA within these areas to be highest in neurons and in choroid plexus epithelium, and moderately lower in ependymal cells lining the ventricles and in vascular endothelial cells. Testican mRNA is not detected in oligodendrocytes or in most astrocytes. However, astrocytes in regions of reactive gliosis do express testican mRNA. These findings, along with a cysteine-rich pattern similarity to neurocan, brevican, versican, and other proteoglycans found in brain, suggest that testican may be a part of the specialized extracellular matrix of the brain. PMID:11131125
Marr, H S; Basalamah, M A; Bouldin, T W; Duncan, A W; Edgell, C J
Different brain components can evolve in a coordinated manner or they can show divergent evolutionary trajectories according to a mosaic pattern of variation. Understanding the relationship between these brain evolutionary patterns, which are not mutually exclusive, can be informed by the examination of intraspecific variation. Our study evaluates patterns of brain anatomical covariation in chimpanzees and humans to infer their influence on brain evolution in the hominin clade. We show that chimpanzee and human brains have a modular structure that may have facilitated mosaic evolution from their last common ancestor. Spatially adjacent regions covary with one another to the strongest degree and separated regions are more independent from each other, which might be related to a predominance of local association connectivity. Despite the undoubted importance of developmental and functional factors in determining brain morphology, we find that these constraints are subordinate to the primary effect of local spatial interactions. PMID:25047085
Gómez-Robles, Aida; Hopkins, William D; Sherwood, Chet C
Summary Understanding how the brain manages billions of processing units connected via kilometers of fibers and trillions of synapses, while consuming a few tens of Watts could provide the key to a completely new category of hardware (neuromorphic computing systems). In order to achieve this, a paradigm shift for computing as a whole is needed, which will see it moving away from current “bit precise” computing models and towards new techniques that exploit the stochastic behavior of simple, reliable, very fast, low-power computing devices embedded in intensely recursive architectures. In this paper we summarize how these objectives will be pursued in the Human Brain Project.
Calimera, Andrea; Macii, Enrico; Poncino, Massimo
Understanding how the brain manages billions of processing units connected via kilometers of fibers and trillions of synapses, while consuming a few tens of Watts could provide the key to a completely new category of hardware (neuromorphic computing systems). In order to achieve this, a paradigm shift for computing as a whole is needed, which will see it moving away from current "bit precise" computing models and towards new techniques that exploit the stochastic behavior of simple, reliable, very fast, lowpower computing devices embedded in intensely recursive architectures. In this paper we summarize how these objectives will be pursued in the Human Brain Project. PMID:24139655
Calimera, Andrea; Macii, Enrico; Poncino, Massimo
Do speakers know universal restrictions on linguistic elements that are absent from their language? We report an experimental test of this question. Our case study concerns the universal restrictions on initial consonant sequences, onset clusters (e.g., bl in block). Across languages, certain onset clusters (e.g., lb) are dispreferred (e.g., systematically under-represented) relative to others (e.g., bl). We demonstrate such preferences among Korean speakers, whose language lacks initial C1C2 clusters altogether. Our demonstration exploits speakers' well known tendency to misperceive ill-formed clusters. We show that universally dispreferred onset clusters are more frequently misperceived than universally preferred ones, indicating that Korean speakers consider the former cluster-type more ill-formed. The misperception of universally ill-formed clusters is unlikely to be due to a simple auditory failure. Likewise, the aversion of universally dispreferred onsets by Korean speakers is not explained by English proficiency or by several phonetic and phonological properties of Korean. We conclude that language universals are neither relics of language change nor are they artifacts of generic limitations on auditory perception and motor control—they reflect universal linguistic knowledge, active in speakers' brains.
Berent, Iris; Lennertz, Tracy; Jun, Jongho; Moreno, Miguel A.; Smolensky, Paul
We studied a sample of 75 Chinese, 73 Malay, and 29 Indian healthy neonates taking part in a cohort study to examine potential differences in neonatal brain morphology and white matter microstructure as a function of ethnicity using both structural T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We first examined the differences in global size and morphology of the brain among the three groups. We then constructed the T2-weighted MRI and DTI atlases and employed voxel-based analysis to investigate ethnic differences in morphological shape of the brain from the T2-weighted MRI, and white matter microstructure measured by fractional anisotropy derived from DTI. Compared with Malay neonates, the brains of Indian neonates’ tended to be more elongated in anterior and posterior axis relative to the superior-inferior axis of the brain even though the total brain volume was similar among the three groups. Although most anatomical regions of the brain were similar among Chinese, Malay, and Indian neonates, there were anatomical variations in the spinal-cerebellar and cortical-striatal-thalamic neural circuits among the three populations. The population-related brain regions highlighted in our study are key anatomical substrates associated with sensorimotor functions.
Bai, Jordan; Abdul-Rahman, Muhammad Farid; Rifkin-Graboi, Anne; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M.; Gluckman, Peter D.; Fortier, Marielle V.; Meaney, Michael J.; Qiu, Anqi
A prototype of an interactive digital brain atlas was developed by using the Visible Human Project data set of the National Library of Medicine. This data set provides corresponding axial magnetic resonance images, computed tomographic images, and cryosections of the brain. The prototype was developed to demonstrate the techniques and methods that will be used throughout the development process of the atlas. The atlas has a graphical user interface, supports user interaction with various representations of the brain (i.e., two-dimensional and three-dimensional [3D]), and displays multiple images simultaneously. Motion sequences of the 3D brain were incorporated in the atlas to provide an important link between two-dimensional brain slices and volume-rendered 3D anatomic structures. Volume visualization tools were used to interactively render, rotate, and reslice the volumetric brain data. The brain was segmented with manual tracing, thresholding, and morphologic algorithms and then rendered with volume-rendering tools. PMID:8888399
Toh, M Y; Falk, R B; Main, J S
Age is one of the key risk factors of several human neurodegenerative disorders such as Alzheimer?s disease and Parkinson?s disease. During aging the immune system of the brain undergoes multiple structural and functional changes. The major immune cells of the brain - microglia and astrocytes - significantly change their morphology and functional state during aging. Similarly, the blood brain barrier (BBB), that is considered to be the iron curtain protecting the brain parenchyma against invasion of the pathogens, can be influenced by aging. This state of altered brain immunity may lead to the increased brain vulnerability to viral infections, primoinfection as well as reactivation. We hypothesize that impairment of the brain immunity and BBB integrity can create the optimal condition for viral infection that can further amplify the neuroinflammation mediated by glial cells and neurodegeneration induced and driven by disease modified proteins. PMID:24020754
Marošová, L; Neradil, P; Zilka, N
Knowledge of the role of brain maturation in the development of cognitive abilities derives primarily from studies of school-age children to adults. Little is known about the morphological features of the neonatal brain that support the subsequent development of abilities in early childhood, when maturation of the brain and these abilities are the most dynamic. The goal of our study was to determine whether brain morphology during the neonatal period supports early cognitive development through 2 years of age. We correlated morphological features of the cerebral surface assessed using deformation-based measures (surface distances) of high-resolution MRI scans for 33 healthy neonates, scanned between the first to sixth week of postmenstrual life, with subsequent measures of their motor, language, and cognitive abilities at ages 6, 12, 18, and 24 months. We found that morphological features of the cerebral surface of the frontal, mesial prefrontal, temporal, and occipital regions correlated with subsequent motor scores, posterior parietal regions correlated with subsequent language scores, and temporal and occipital regions correlated with subsequent cognitive scores. Measures of the anterior and middle portions of the cingulate gyrus correlated with scores across all three domains of ability. Most of the significant findings were inverse correlations located bilaterally in the brain. The inverse correlations may suggest either that a more protracted morphological maturation or smaller local volumes of neonatal brain tissue supports better performance on measures of subsequent motor, language, and cognitive abilities throughout the first 2 years of postnatal life. The correlations of morphological measures of the cingulate with measures of performance across all domains of ability suggest that the cingulate supports a broad range of skills in infancy and early childhood, similar to its functions in older children and adults. Hum Brain Mapp 35:4459-4474, 2014. © 2014 Wiley Periodicals, Inc. PMID:24615961
Spann, Marisa N; Bansal, Ravi; Rosen, Tove S; Peterson, Bradley S
Background Phenotypic integration among different anatomical parts of the head is a common phenomenon across vertebrates. Interestingly, despite centuries of research into the factors that contribute to the existing variation in brain size among vertebrates, little is known about the role of phenotypic integration in brain size diversification. Here we used geometric morphometrics on the morphologically diverse Tanganyikan cichlids to investigate phenotypic integration across key morphological aspects of the head. Then, while taking the effect of shared ancestry into account, we tested if head shape was associated with brain size while controlling for the potentially confounding effect of feeding strategy. Results The shapes of the anterior and posterior parts of the head were strongly correlated, indicating that the head represents an integrated morphological unit in Lake Tanganyika cichlids. After controlling for phylogenetic non-independence, we also found evolutionary associations between head shape, brain size and feeding ecology. Conclusions Geometric morphometrics and phylogenetic comparative analyses revealed that the anterior and posterior parts of the head are integrated, and that head morphology is associated with brain size and feeding ecology in Tanganyikan cichlid fishes. In light of previous results on mammals, our results suggest that the influence of phenotypic integration on brain diversification is a general process.
Self-organized criticality is an attractive model for human brain dynamics, but there has been little direct evidence for its existence in large-scale systems measured by neuroimaging. In general, critical systems are associated with fractal or power law scaling, long-range correlations in space and time, and rapid reconfiguration in response to external inputs. Here, we consider two measures of phase synchronization: the phase-lock interval, or duration of coupling between a pair of (neurophysiological) processes, and the lability of global synchronization of a (brain functional) network. Using computational simulations of two mechanistically distinct systems displaying complex dynamics, the Ising model and the Kuramoto model, we show that both synchronization metrics have power law probability distributions specifically when these systems are in a critical state. We then demonstrate power law scaling of both pairwise and global synchronization metrics in functional MRI and magnetoencephalographic data recorded from normal volunteers under resting conditions. These results strongly suggest that human brain functional systems exist in an endogenous state of dynamical criticality, characterized by a greater than random probability of both prolonged periods of phase-locking and occurrence of large rapid changes in the state of global synchronization, analogous to the neuronal "avalanches" previously described in cellular systems. Moreover, evidence for critical dynamics was identified consistently in neurophysiological systems operating at frequency intervals ranging from 0.05-0.11 to 62.5-125 Hz, confirming that criticality is a property of human brain functional network organization at all frequency intervals in the brain's physiological bandwidth. PMID:19300473
Kitzbichler, Manfred G; Smith, Marie L; Christensen, Søren R; Bullmore, Ed
In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.
A quarter-century ago visual neuroscientists had little information about the number and organization of retinotopic maps in human visual cortex. The advent of functional magnetic resonance imaging (MRI), a non-invasive, spatially-resolved technique for measuring brain activity, provided a wealth of data about human retinotopic maps. Just as there are differences amongst nonhuman primate maps, the human maps have their own unique properties. Many human maps can be measured reliably in individual subjects during experimental sessions lasting less than an hour. The efficiency of the measurements and the relatively large amplitude of functional MRI signals in visual cortex make it possible to develop quantitative models of functional responses within specific maps in individual subjects. During this last quarter century, there has also been significant progress in measuring properties of the human brain at a range of length and time scales, including white matter pathways, macroscopic properties of gray and white matter, and cellular and molecular tissue properties. We hope the next twenty-five years will see a great deal of work that aims to integrate these data by modeling the network of visual signals. We don’t know what such theories will look like, but the characterization of human retinotopic maps from the last twenty-five years is likely to be an important part of future ideas about visual computations.
Wandell, Brian A.; Winawer, Jonathan
We present a new technique for segmentation of skull in human T1-weighted magnetic resonance (MR) images that generates realistic models of the head for EEG and MEG source modeling. Our method performs skull segmentation using a sequence of mathematical morphological operations. Prior to the segmentation of skull, we segment the scalp and the brain from the MR image. The scalp mask allows us to quickly exclude background voxels with intensities similar to those of the skull, while the brain mask obtained from our Brain Surface Extractor algorithm ensures that the brain does not intersect our skull segmentation. We find the inner and the outer skull boundaries using thresholding and morphological closing and opening operations. We then mask the results with the scalp and brain volumes to ensure closed and nonintersecting skull boundaries. We applied our scalp and skull segmentation algorithm to several MR images and validated our method using coregistered CT-MR image data sets. We observe that our method is capable of producing scalp and skull segmentations suitable for MEG and EEG source modeling in 3D T1-weighted human MR images.
Dogdas, Belma; Shattuck, David W.; Leahy, Richard M.
In view of the recent advance in functional neuroimaging, the current status of non-invasive techniques applied for human brain mapping was reviewed by integrating two principles: hemodynamic and electrophysiological, from the viewpoint of clinical neurophysiology. The currently available functional neuroimaging techniques based on hemodynamic principles are functional magnetic resonance imaging (fMRI), positron emission tomography (PET) or single-photon emission computed tomography
Animal data suggest that the widely abused psychostimulant methamphetamine can damage brain dopamine neurones by causing dopamine-dependent oxidative stress; however, the relevance to human methamphetamine users is unclear. We measured levels of key antioxidant defences (reduced (GSH) and oxidized (GSSG) glutathione, six major GSH system enzymes, copper-zinc superoxide dismutase (CuZnSOD), uric acid) that are often altered after exposure to oxidative
Anna Mirecki; Paul Fitzmaurice; Lee Ang; Kathryn S. Kalasinsky; Frank J. Peretti; Sally S. Aiken; Dennis J. Wickham; Allan Sherwin; Henry J. Forman; Stephen J. Kish
The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM). PMID:19381963
Hou, Bob L; Hu, Jiani
Article abstract—Objective: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation. Methods: Regional brain volumes were measured in 10 subjects with KS
A. J. Patwardhan; S. Eliez; B. Bender; M. G. Linden; A. L. Reiss
Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.
Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.
As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge. PMID:23301101
Friedrich, Roland M; Friederici, Angela D
Dimethyl sulfoxide (DMSO) opens the blood-brain barrier of mice to the enzymatic tracer horseradish peroxidase. A single injection of horseradish peroxidase in 10 to 15 percent DMSO into the tail vein along with 10 to 15 percent DMSO delivered intraperitoneally allowed horseradish peroxidase to fill the extracellular clefts throughout the brain within 2 hours. In the absence of DMSO, peroxidase failed to enter brain parenchyma except through the circumventricular organs. Opening of the blood-brain barrier by DMSO is reversible. Dimethyl sulfoxide stimulated the pinocytosis of horseradish peroxidase by the cerebral endothelium; the peroxidase was then directed to lysosomal dense bodies for degradation. Vesicular transport of horseradish peroxidase from the luminal to the abluminal wall of the endothelial cell was not observed. Dimethyl sulfoxide did not alter the morphology of endothelial cells or brain parenchyma.
Broadwell, Richard D.; Salcman, Michael; Kaplan, Richard S.
Background The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS) are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas. Methods Adults with PDS (n = 10) and controls (n = 10) matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM) the brains of stutterers and non-stutterers were compared with respect to white matter (WM) and grey matter (GM) differences. Results We found increased WM volumes in a right-hemispheric network comprising the superior temporal gyrus (including the planum temporale), the inferior frontal gyrus (including the pars triangularis), the precentral gyrus in the vicinity of the face and mouth representation, and the anterior middle frontal gyrus. In addition, we detected a leftward WM asymmetry in the auditory cortex in non-stutterers, while stutterers showed symmetric WM volumes. Conclusions These results provide strong evidence that adults with PDS have anomalous anatomy not only in perisylvian speech and language areas but also in prefrontal and sensorimotor areas. Whether this atypical asymmetry of WM is the cause or the consequence of stuttering is still an unanswered question.
Jancke, Lutz; Hanggi, Jurgen; Steinmetz, Helmuth
This book examines new methods of molecular biology that are providing valuable insights into the human brain, the genes that govern its assembly and function, and the many genetic defects that cause neurological diseases such as Alzheimer's, Cri du Chat syndrome, Huntington's disease, and bipolar depression disorder. In addition, the book reviews techniques in molecular neurobiological research, including the use of affinity reagents, chimeric receptors, and site-directed mutagenesis in localizing the ion channel and cholinergic binding site, and the application of somatic cell genetics in isolating specific chromosomes or chromosomal segments.
One of the important applications of ultrasound hyperthermia is temperature elevation at specified locations in the human brain. The ultrasound applicator used is a circular phased array surrounding the human head. The human head model is assumed to be two concentric spheres of skin and bone containing a hemisphere of brain. The single and multiple foci patterns of the ultrasound
N. H. Ismail; A. T. Ibrahim
Our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from Neanderthals–Denisovans and that gave us a more globular braincase configuration. In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny.
Boeckx, Cedric; Benitez-Burraco, Antonio
Though it is widely appreciated that complex structural, functional and morphological relationships exist between distinct areas of the human cerebral cortex, the extent to which such relationships coincide remains insufficiently appreciated. Here we determine the extent to which correlations between brain regions are modulated by either structural, connectomic or network-theoretic properties using a structural neuroimaging data set of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volumes acquired from N = 110 healthy human adults. To identify the linear relationships between all available pairs of regions, we use canonical correlation analysis to test whether a statistically significant correlation exists between each pair of cortical parcels as quantified via structural, connectomic or network-theoretic measures. In addition to this, we investigate (1) how each group of canonical variables (whether structural, connectomic or network-theoretic) contributes to the overall correlation and, additionally, (2) whether each individual variable makes a significant contribution to the test of the omnibus null hypothesis according to which no correlation between regions exists across subjects. We find that, although region-to-region correlations are extensively modulated by structural and connectomic measures, there are appreciable differences in how these two groups of measures drive inter-regional correlation patterns. Additionally, our results indicate that the network-theoretic properties of the cortex are strong modulators of region-to-region covariance. Our findings are useful for understanding the structural and connectomic relationship between various parts of the brain, and can inform theoretical and computational models of cortical information processing.
Irimia, Andrei; Van Horn, John D.
IRDA (intermittent rhythmic delta activity) is an abnormal generalized EEG pattern that is not specific to any single etiology and can occur with diffuse or focal cerebral disturbances. To determine whether different electrographic features of IRDA and associated EEG findings can differentiate underlying focal from diffuse brain disturbances, we performed a blind analysis of 58 consecutive EEGs with an IRDA pattern, recorded from 1993 until 1996, in which we evaluated posterior background activity, focal slowing and IRDA characteristics (frequency, distribution, duration, symmetry and abundance). The clinical diagnosis, state of consciousness and CT brain findings were retrieved from the patients' hospital records. There were 58 patients (33 females; mean age, 58+/-21 years). Twelve (21%) had only focal brain lesions, while 46 (79%) had diffuse brain abnormalities, (15 diffuse structural, 19 metabolic abnormalities, 12 postictal). Normal consciousness and focal EEG slowing were more frequent in patients with focal abnormalities, however, this was not statistically significant. Of the patients with focal abnormality, 11 (92%) had normal posterior background activity either bilaterally (n=4) or contralateral to the focal lesion (n=7). Bilaterally normal posterior background activity was observed in about 30% in both groups. Bilaterally abnormal posterior background activity was apparent in one patient (8%) with focal brain lesion and in 31 patients (67%) with diffuse brain abnormalities (P<0.0001). There were no significant differences in IRDA electrographic features between the focal group and the group with diffuse brain disturbances. We conclude that IRDA morphology cannot distinguish between focal and diffuse brain abnormalities. PMID:10385048
Neufeld, M Y; Chistik, V; Chapman, J; Korczyn, A D
Background Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of childhood epilepsy, but the neuroanatomical correlates of ADHD in epilepsy have yet to be comprehensively characterized. Methods Children with new and recent-onset epilepsy with (n?=?18) and without (n?=?36) ADHD, and healthy controls (n?=?46) underwent high resolution MRI. Measures of cortical morphology (thickness, area, volume, curvature) and subcortical and cerebellar volumes were compared between the groups using the program FreeSurfer 5.1. Results Compared to the control group, children with epilepsy and ADHD exhibited diffuse bilateral thinning in the frontal, parietal and temporal lobes, with volume reductions in the brainstem and subcortical structures (bilateral caudate, left thalamus, right hippocampus). There were very few group differences across measures of cortical volume, area or curvature. Conclusions Children with epilepsy and comorbid ADHD exhibited a pattern of bilateral and widespread decreased cortical thickness as well as decreased volume of subcortical structures and brainstem. These anatomic abnormalities were evident early in the course of epilepsy suggesting the presence of antecedent neurodevelopmental changes, the course of which remains to be determined.
Saute, Ricardo; Dabbs, Kevin; Jones, Jana E.; Jackson, Daren C.; Seidenberg, Michael; Hermann, Bruce P.
Inhaled anesthetics bind specifically to a wide variety of proteins in the brain. This set of proteins must include those that contribute to the physiological and behavioral phenotypes of anesthesia and the related side effects. To identify the anesthetic-binding targets and functional pathways associated with these targets in human brain, halothane photolabeling and two-dimensional (2D) gel electrophoresis were used. Both membrane and soluble proteins from human temporal cortex were prepared. More than 300 membrane and 400 soluble protein spots were detected on the stained blots, of which 23 membrane and 34 soluble proteins were labeled by halothane and identified by mass spectroscopy. Their functional classification reveals five groups, including carbohydrate metabolism, protein folding, oxidative phosphorylation, nucleoside triphosphatase, and dimer/kinase activity with different correlative stringency. When network analysis of the interaction between these protein molecules is used, the weighted interaction accentuates the cellular protein components important in cell growth and proliferation, cell cycle and cell death, and cell-cell signaling and interactions, although no pathway was specific. This study provides evidence for multiple anesthetic binding targets and suggests potential pathways involved in their actions. PMID:17269715
Pan, Jonathan Z; Xi, Jin; Tobias, John W; Eckenhoff, Maryellen F; Eckenhoff, Roderic G
Through 40 years of neuropathological practice,the Brain Research Institute, University of Niigata (BRI-Niigata), Japan has accumulated extensive human brain resource,including fresh-frozen brain slices,for scientific research. Over 30,000 slices obtained from consecutive autopsies have been systematically stored in 25 deep freezers. Establishment of effective networks between brain banks and institutional collections in Japan is essential for promoting scientific activities that require human brain resource. We at the BRI-Niigata are eager to contribute to the establishment of such networks. PMID:20940500
Kakita, Akiyoshi; Takahashi, Hitoshi
Neuroscientists have long observed that brain activity is naturally variable from moment-to-moment, but neuroimaging research has largely ignored the potential importance of this phenomenon. An emerging research focus on within-person brain signal variability is providing novel insights, and offering highly predictive, complementary, and even orthogonal views of brain function in relation to human life-span development, cognitive performance, and various clinical conditions. As a result, brain signal variability is evolving as a bona fide signal of interest, and should no longer be dismissed as meaningless noise when mapping the human brain.
Garrett, Douglas D.; Samanez-Larkin, Gregory R.; MacDonald, Stuart W.S.; Lindenberger, Ulman; McIntosh, Anthony R.; Grady, Cheryl L.
There are hundreds or thousands of endothelial cells around the perimeter of a single artery or vein, and hence an individual cell experiences little curvature. In contrast, a single endothelial cell may wrap around itself to form the lumen of a brain capillary. Curvature plays a key role in many biological, chemical and physical processes, however, its role in dictating the morphology and polarization of brain capillary endothelial cells has not been investigated. We hypothesize that curvature and shear flow play a key role in determining the structure and function of the blood-brain barrier (BBB). We have developed the ``rod'' assay to study the influence of curvature on the morphology of confluent monolayers of endothelial cells. In this assay cells are plated onto glass rods pulled down to the desired diameter in the range from 5 -- 500 ?m and coated with collagen. We show that curvature has a significant influence on the morphology of endothelial cells and may have an important role in blood-brain barrier function.
Ye, Mao; Yang, Zhen; Wong, Andrew; Searson, Peter
Examines the implications of the left brain-right brain theory on communications styles in male-female relationships. The author contends that women tend to use the vagueness of their emotional responses manipulatively. Men need to apply rational approaches to increase clarity in communication. (AM)
In this study of the effect of bipolar status and presence of BDNF Val66Met polymorphism on differences in regional brain volumes, we hypothesized based on previous studies that 1) bipolar subjects will have smaller regional brain volumes than healthy controls; 2) BDNF Met66 allele carriers within the same population are likely to have smaller regional brain volumes as compared to Val66 homozygyotes. In our Caucasian sample of 166 bipolar subjects and 64 gender-matched healthy controls, we found significant decreases in total (p?=?0.005) and regional gray matter volumes in bipolar patients compared to healthy controls, more pronounced in the inferior and posterior parts of the brain, together with a concomitant increase in total CSF (p?=?0.012) particularly in the lateral ventricles (p?=?0.023). However, there was no difference in white matter volumes noted by other studies. Furthermore we did not find significant differences in other brain regions that have been reported by other authors. Nor did we find a significant effect of BDNF on these measurements.
Teh, Cheryl Ann; Lee, Tih-Shih; Kuchibhatla, Margaratha; Ashley-Koch, Allison; MacFall, James; Krishnan, Ranga; Beyer, John
?-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 ?-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. PMID:24474688
Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry
It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6-8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children. PMID:24096296
El Marroun, Hanan; Schmidt, Marcus N; Franken, Ingmar H A; Jaddoe, Vincent W V; Hofman, Albert; van der Lugt, Aad; Verhulst, Frank C; Tiemeier, Henning; White, Tonya
The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with
Tao Lu; Ying Pan; Shyan-Yuan Kao; Cheng Li; Isaac Kohane; Jennifer Chan; Bruce A. Yankner
The potential for human neuroimaging to read out the detailed contents of a person's mental state has yet to be fully explored. We investigated whether the perception of edge orientation, a fundamental visual feature, can be decoded from human brain activity measured with functional magnetic resonance imaging (fMRI). Using statistical algorithms to classify brain states, we found that ensemble fMRI
Frank Tong; Yukiyasu Kamitani
Reconstruction of Human Lung Morphology Models from Magnetic Resonance Images T. B. Martonen (Experimental Toxicology Division, U.S. EPA, Research Triangle Park, NC 27709) and K. K. Isaacs (School of Public Health, University of North Carolina, Chapel Hill, NC 27514) ...
Background— Experimental studies suggest that arterial injury and inflammation lead to increased neointimal growth after stenting. Despite the increased use of coronary stents in humans, there are only limited pathological data on the morphological features of in-stent restenosis. Methods and Results—Detailed histology was performed on 116 stents, implanted 90 days in 87 coronary arteries, from 56 patients (mean age, 5913
Andrew Farb; Deena K. Weber; Frank D. Kolodgie; Allen P. Burke; Renu Virmani
The aim of the study was an experimental determination of some morphological and mechanical properties of human liver and spleen (amount of collagen in organ capsules, their critical tension and density), followed by a definition of the threshold of critical acceleration, above which the organs can be injured during a car crash. Experiments were done on 33 fresh cadavers (18
J. Stingl; V. Bá?a; P. ?ech; J. Kovanda; H. Kovandová; V. Mandys; J. Rejmontová; B. Sosna
Reported studies describing normal and abnormal aging based on anatomical MRI analysis do not consider morphological brain changes, but only volumetric measures to distinguish among these processes. This work presents a classification scheme, based both on size and shape features extracted from brain volumes, to determine different aging stages: healthy control (HC) adults, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three support vector machines were optimized and validated for the pair-wise separation of these three classes, using selected features from a set of 3D discrete compactness measures and normalized volumes of several global and local anatomical structures. Our analysis show classification rates of up to 98.3% between HC and AD; of 85% between HC and MCI and of 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indexes to classify different aging stages.
Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.
Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology. In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group. Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise. PMID:24291669
Schlaffke, L; Lissek, S; Lenz, M; Brüne, M; Juckel, G; Hinrichs, T; Platen, P; Tegenthoff, M; Schmidt-Wilcke, T
The evolution of higher cognitive functions in humans is thought to be due, at least in part, to the molecular evolution of gene expression patterns specific to the human brain. In this article, we explore recent and past findings using comparative genomics in human and non-human primate brain to identify these novel human patterns. We suggest additional directions and lines of experimentation that should be taken to improve our understanding of these changes on the human lineage. Finally, we attempt to put into context these genomic changes with biological phenotypes and diseases in humans.
Wang, Guang-Zhong; Konopka, Genevieve
Filamentous inclusions made of hyperphosphorylated tau are characteristic of numerous human neurodegenerative diseases, including Alzheimer's disease, tangle-only dementia, Pick disease, argyrophilic grain disease (AGD), progressive supranuclear palsy, and corticobasal degeneration. In Alzheimer's disease and AGD, it has been shown that filamentous tau appears to spread in a stereotypic manner as the disease progresses. We previously demonstrated that the injection of brain extracts from human mutant P301S tau-expressing transgenic mice into the brains of mice transgenic for wild-type human tau (line ALZ17) resulted in the assembly of wild-type human tau into filaments and the spreading of tau inclusions from the injection sites to anatomically connected brain regions. Here we injected brain extracts from humans who had died with various tauopathies into the hippocampus and cerebral cortex of ALZ17 mice. Argyrophilic tau inclusions formed in all cases and following the injection of the corresponding brain extracts, we recapitulated the hallmark lesions of AGD, PSP and CBD. Similar inclusions also formed after intracerebral injection of brain homogenates from human tauopathies into nontransgenic mice. Moreover, the induced formation of tau aggregates could be propagated between mouse brains. These findings suggest that once tau aggregates have formed in discrete brain areas, they become self-propagating and spread in a prion-like manner. PMID:23690619
Clavaguera, Florence; Akatsu, Hiroyasu; Fraser, Graham; Crowther, R Anthony; Frank, Stephan; Hench, Jürgen; Probst, Alphonse; Winkler, David T; Reichwald, Julia; Staufenbiel, Matthias; Ghetti, Bernardino; Goedert, Michel; Tolnay, Markus
Rational decision-making should not be influenced by irrecoverable past costs. Human beings, however, often violate this basic rule of economics and take 'sunk' costs into account when making decisions about current or future investments, thus exhibiting a so-called 'sunk cost effect'. Although the sunk cost effect may have serious political, financial or personal consequences, its neural basis is largely unknown. Using functional magnetic resonance imaging (fMRI) and a novel financial decision-making task, we show here that previous investments reduced the contribution of the ventromedial prefrontal cortex (vmPFC) to current decision-making and that this reduction in vmPFC activity correlated with the sunk cost effect. Moreover, activity in the dorsolateral prefrontal cortex (dlPFC) was associated with the norm not to waste resources and negatively correlated with vmPFC activity. The present findings show how past investments may bias decision-making in the human brain, suggesting that the interaction of vmPFC and dlPFC may promote a tendency to throw good money after bad. PMID:24751949
Haller, Ariane; Schwabe, Lars
Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples.
Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel
Human radial glia (RG) share many of the features described in rodents, but also have a number of characteristics unique to the human brain. Results obtained from different mammalian species including human and non-human primates reveal differences in the involvement of RG in neurogenesis and oligodendrogenesis and in the timing of the initial expression of typical RG immunomarkers. A common problem in studying the human brain is that experimental procedures using modern molecular and genetic methods, such as in vivo transduction with retroviruses or creation of knockout or transgenic mutants, are not possible. Nevertheless, abundant and valuable information about the development of the human brain has been revealed using postmortem human material. Additionally, a combination and spectrum of in vitro techniques are used to gain knowledge about normal developmental processes in the human brain, including better understanding of RG as progenitor cells. Molecular and functional characterization of multipotent progenitors, such as RG, is important for future cell replacement therapies in neurological and psychiatric disorders, which are often resistant to conventional treatments. The protracted time of development and larger size of the human brain could provide insight into processes that may go unnoticed in the much smaller rodent cortex, which develops over a much shorter period. With that in mind, we summarize results on the role of RG in the human fetal brain.
Howard, Brian M.; Mo, Zhicheng; Filipovic, Radmila; Moore, Anna R.; Antic, Srdjan D.; Zecevic, Nada
Background Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life. However, the incidence of aneuploidy in the developing human brain and its impact on the brain development and function are obscure. Methodology/Principal Findings To address genomic variation during development we surveyed aneuploidy/polyploidy in the human fetal tissues by advanced molecular-cytogenetic techniques at the single-cell level. Here we show that the human developing brain has mosaic nature, being composed of euploid and aneuploid neural cells. Studying over 600,000 neural cells, we have determined the average aneuploidy frequency as 1.25–1.45% per chromosome, with the overall percentage of aneuploidy tending to approach 30–35%. Furthermore, we found that mosaic aneuploidy can be exclusively confined to the brain. Conclusions/Significance Our data indicates aneuploidization to be an additional pathological mechanism for neuronal genome diversification. These findings highlight the involvement of aneuploidy in the human brain development and suggest an unexpected link between developmental chromosomal instability, intercellural/intertissular genome diversity and human brain diseases.
Liehr, Thomas; Kolotii, Alexei D.; Kutsev, Sergei I.; Pellestor, Franck; Beresheva, Alfia K.; Demidova, Irina A.; Kravets, Viktor S.; Monakhov, Viktor V.; Soloviev, Ilia V.
The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.
Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.
Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee
Mario Cáceres; Joel Lachuer; Lili Kudo; Daniel H. Geschwind; David J. Lockhart; Todd M. Preuss; Carrolee Barlow
A major attraction of voxel-based morphometry (VBM) is that it allows researchers to explore large datasets with minimal human intervention. However, the validity and sensitivity of the Statistical Parametric Mapping (SPM2) approach to VBM are the subject of considerable debate. We visually inspected the SPM2 gray matter segmentations for 101 research participants and found a gross inclusion of non-brain tissue
George Fein; Bennett Landman; Hoang Tran; Jerome Barakos; Kirk Moon; Victoria Di Sclafani; Robert Shumway
Nineteen human cadaver corneas with few damaged endothelial cells were incubated under tissue culture conditions for time periods ranging from five min to 48 h. Morphological alterations of the endothelial cells were studied in whole wet mounts stained by alizarine red-alkohol-trypane blue and by scanning electron microscopy. Joint meetings of three cells are characteristic for normal corneal endothelium. After 15--60 min of incubation, damaged cells were expelled from the coherent cell sheet by expanding neighbouring cells. Joint meetings of 5--8 expanding cells were formed. After 24 h of incubation, joint meetings of four cells were the dominating morphological abnormality. Morphological changes during reduction of the numbers of cells in joint meetings are described. PMID:80914
Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function. PMID:22581850
Navarrete, Marta; Perea, Gertrudis; Maglio, Laura; Pastor, Jesús; García de Sola, Rafael; Araque, Alfonso
The present study considers patterns of brain morphology in 14 common species of mid-European Cyprinidae. Sixteen areas per brain were measured on serial cryostat sections by computer-aided planimetry. The volumes of these areas were expressed as % of the total brain volume. These brain centres (ranked according to falling values of the coefficient of variation VR, of the interspecific mean) are: Lobus facialis, L. vagus, central acustic area, Crista cerebellaris, Bulbus olfactorius, Eminentia granularis, Stratum opticum (of the optic tectum), Torus longitudinalis, Nucleus habenularis, Valvula cerebelli, Corpus cerebelli, Telencephalon, Tectum opticum, Diencephalon, Torus semicircularis, mesencephalic tegmentum. Seven primary sensory areas are leading in VR; highest in interspecific variability were the two special viscerosensory brainstem lobes for external (L. facialis) and internal (L. vagus) taste. Low in interspecific variability were integration centres (see above). By plotting the relative volumina of those brain centres which represent three major sensory modalities: brain stem chemosense, acoustico-lateralis and sense of vision, species are separated into three groups: 1) Most species scatter along an axis from moderately (Aspius aspius, Rutilus rutilus, Leuciscus cephalus, Scardinius erythrophthalmus, Alburnus alburnus, Chondrostoma nasus) to highly developed chemo- and acustico-lateralis centres (Vimba vimba, Abramis brama, Abramis ballerus). Blicca bjoercna is situated in the middle of this axis. Within the latter group the optic centres are evenly well developed. 2) Carassius carassius, Gobio gobio and Tinca tinca are characterized by relatively small acoustico-lateralis and optic areas, but highly developed chemocentres. 3) Pelecus cultratus is monotypic among the species investigated by having large acoustico-lateralis and optic, but modestly developed chemocentres. The brain patterns relative to life style are discussed. PMID:3418119
Kotrschal, K; Junger, H
The skull is considered a modular structure in which different parts are influenced by different factors and, as a result, achieve adult shape at different ages. Previous studies have suggested that the basicranium presents a modular pattern that distinguishes sagittal and lateral parts, probably affected by the brain and masticatory structures, respectively. The vault of modern humans, in contrast, has been considered as a highly integrated system mainly influenced by brain growth. Here, we explored developmental shape variation in sagittal and lateral ectocranial vault in humans in order to assess if both regions are ontogenetically dissociated. We used a sample of 135 cranial computed tomography images from 0 to 31 ages. Landmarks and semilandmarks were collected on sagittal and lateral regions and geometric morphometric techniques were applied separately for each region. On the shape coordinates, we used Goodall's F-test in order to assess the age when the adult configuration is attained. Principal component analysis enabled us to evaluate shape variation during ontogeny. Results indicated that both sagittal and lateral structures attain adult shape at early adolescence. Both regions express coordinated shape modifications probably due to shared developmental factors. It is concluded that masticatory muscles may not exert a strong enough influence to produce independent variation in the lateral traits. Thus, it is likely that the brain integrates sagittal and lateral parts of the vault across human ontogeny. PMID:23674354
Anzelmo, Marisol; Barbeito-Andrés, Jimena; Ventrice, Fernando; Pucciarelli, Héctor M; Sardi, Marina L
The complexity of the human brain has made it difficult to study many brain disorders in model organisms, and highlights the need for an in vitro model of human brain development. We have developed a human pluripotent stem cell-derived 3D organoid culture system, termed cerebral organoid, which develops various discrete though interdependent brain regions. These include cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNAi and patient-specific iPS cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could explain the disease phenotype. Our data demonstrate that 3D organoids can recapitulate development and disease of even this most complex human tissue.
Lancaster, Madeline A.; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S.; Hurles, Matthew E.; Homfray, Tessa; Penninger, Josef M.; Jackson, Andrew P.; Knoblich, Juergen A.
The goal of this study is twofold: (1) to assess brain anatomical differences between children meeting diagnostic criteria for oppositional defiant disorder (ODD) and healthy controls, and (2) to investigate whether morphological brain characteristics associated with ODD differ in boys and girls. Eight-year-old participants (N = 38) were scanned…
Fahim, Cherine; Fiori, Marina; Evans, Alan C.; Perusse, Daniel
Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin ? II, and ?- and ?-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in ?-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in ?-spectrin protein levels, and a significant increase in transmembranous ?3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of ?-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic ?- and ?-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics. PMID:24699688
Erdozain, Amaia M; Morentin, Benito; Bedford, Lynn; King, Emma; Tooth, David; Brewer, Charlotte; Wayne, Declan; Johnson, Laura; Gerdes, Henry K; Wigmore, Peter; Callado, Luis F; Carter, Wayne G
Understanding the evolutionary consequences of anthropogenic change is an emerging topic in evolutionary biology. While highly sensitive species may go extinct in response to anthropogenic habitat alteration, those with broader environmental tolerances may persist and adapt to the changes. Here, we use morphological data from the brown anole (Anolis sagrei), a lizard species that lives in both natural and human-disturbed habitats, to examine the impact of anthropogenic habitat alteration. We find populations inhabiting disturbed habitats were significantly larger in snout-vent length, hindspan, and mass and provide evidence that the observed divergence in hindspan is driven by human-induced changes in habitat structure. Populations were found to be genetically distinct among islands but are not genetically differentiated between habitat types on islands. Thus, the observed pattern of intra-island morphological differences cannot be explained by separate founding populations. Rather, our results are consistent with morphological differences between habitats having arisen in situ on each island. Results underscore the significant impact anthropogenic change may have on evolutionary trajectories of populations that persist in human-altered habitats.
Marnocha, Erin; Pollinger, John; Smith, Thomas B
This paper provides a new perspective on human motion with an investigation of whether and how patterns of human mobility inside cities are affected by two urban morphological characteristics: compactness and size. Mobile phone data have been collected in eight cities in Northeast China and used to extract individuals’ movement trajectories. The massive mobile phone data provides a wide coverage and detailed depiction of individuals’ movement in space and time. Considering that most individuals’ movement is limited within particular urban areas, boundaries of urban agglomerations are demarcated based on the spatial distribution of mobile phone base towers. Results indicate that the distribution of human’s intra-urban travel in general follows the exponential law. The exponents, however, vary from city to city and indicate the impact of city sizes and shapes. Individuals living in large or less compact cities generally need to travel farther on a daily basis, and vice versa. A Monte Carlo simulation analysis based on Levy flight is conducted to further examine and validate the relation between intra-urban human mobility and urban morphology.
Kang, Chaogui; Ma, Xiujun; Tong, Daoqin; Liu, Yu
For a long time, researchers have been working on a marriage of human and machine that sounds like something out of science fiction: a brain-computer interface. BCIs read electrical signals or other manifestations of brain activity and translate them into a digital form that computers can understand, process, and convert into actions of some kind, such as moving a cursor
Sixto Ortiz Jr.
The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI)
Tom M. Mitchell; Svetlana V. Shinkareva; Andrew Carlson; Kai-Min Chang; Vicente L. Malave; Robert A. Mason; Marcel Adam Just
Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool
Patric Hagmann; Maciej Kurant; Xavier Gigandet; Patrick Thiran; Van J. Wedeen; Reto Meuli
The human brain is found to produce a magnetic field near the scalp which varies in synchrony with periodic electrical stimulation applied to a finger. Use of a highly sensitive superconducting quantum interference device as a magnetic field detector reveals that the brain's field is sharply localized over the primary projection area of the sensory cortex contralateral to the digit
D. Brenner; J. Lipton; L. Kaufman; S. J. Williamson
Background Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and tissue. Methods Primary human brain cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells were treated with pro-inflammatory compounds IFN?, TNF?, IL-1?, and LPS, and chemokines IP-10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR. Microarray analysis was also performed on late passage cultures treated with vehicle or IFN? and IL-1?. Results Early passage human brain cell cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes. Later passage cultures contained proliferating fibroblasts and pericytes only. Under basal culture conditions all cell types showed cytoplasmic NF?B indicating that they were in a non-activated state. Expression of IP-10 and MCP-1 were significantly increased in response to pro-inflammatory stimuli. The two chemokines were expressed in mixed cultures as well as cultures of fibroblasts and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA and protein level, and both were secreted into cell culture media. NF?B nuclear translocation was also detected in response to pro-inflammatory cues (except IFN?) in all cell types. Microarray analysis of brain pericytes also revealed widespread changes in gene expression in response to the combination of IFN? and IL-1? treatment including interleukins, chemokines, cellular adhesion molecules and much more. Conclusions Adult human brain cells are sensitive to cytokine challenge. As expected ‘classical’ brain immune cells, such as microglia and astrocytes, responded to cytokine challenge but of even more interest, brain pericytes also responded to such challenge with a rich repertoire of gene expression. Immune activation of brain pericytes may play an important role in communicating inflammatory signals to and within the brain interior and may also be involved in blood brain barrier (BBB) disruption . Targeting brain pericytes, as well as microglia and astrocytes, may provide novel opportunities for reducing brain inflammation and maintaining BBB function and brain homeostasis in human brain disease.
In their natural auditory environment, humans are faced with a highly complex array of stimulus sources of varying location, frequency, and intensity, usually overlapping in time. This three- dimensional auditory space is to be analysed and represented by the human brain for the organism to function adequately. Slightly simplifying, the human auditory cortex can be described as a two- dimensional
H. Tiitinen; K. Palomäki; V. Mäkinen; P. May; P. Alku
Belliveau JW, Kwong KK, Kennedy DN, Baker JR, Stern CE, Benson R, Chesler DA, Weisskoff RM, Cohen MS, Tootell RBH, Fox PT, Brady TJ, Rosen BR. Magnetic resonance imaging mapping of brain function: human visual cortex. Invest Radiol 1992;27:SS9–S65. Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology of MRI brain mapping and results from the investigation of the functional organization and frequency response of human primary visual cortex (Vl) are presented.
BELLIVEAU, J.W.; KWONG, K.K.; KENNEDY, D.N.; BAKER, J.R.; STERN, C.E.; BENSON, R.; CHESLER, D.A.; WEISSKOFF, R.M.; COHEN, M.S.; TOOTELL, R.B.H.; FOX, P.T.; BRADY, T.J.; ROSEN, B.R.
This article describes a recent workshop at which advancements in the study of the structure and function of the brain were discussed. Although studies utilizing techniques of MRI, electroencephalography and magnetoencephalography have been useful, positron emission tomography is the only technique capable, at present, of giving images of activity across the entire brain.
Substance abuse is the most prevalent comorbid psychiatric condition associated with schizophrenia, and cannabis is the illicit drug most often abused. Apart from worsening the course of schizophrenia, frequent cannabis use especially at an early age seems to be an important risk factor for developing schizophrenia. Although a large body of neuroimaging studies gives evidence for structural alterations in many different brain regions in schizophrenia patients, there is still limited knowledge of the impact of cannabis abuse on brain structure in schizophrenia. We performed a systematic review including structural magnetic resonance imaging studies comparing high-risk and schizophrenia patients with and without cannabis abuse and found inconclusive results. While there is some evidence that chronic cannabis abuse could alter brain morphology in schizophrenia in patients continuing their cannabis consumption, there is no convincing evidence that this alteration takes place before the onset of schizophrenia when looking at first-episode patients. There is some weak evidence that cannabis abuse could affect brain structures in high-risk subjects, but replication of these studies is needed. PMID:22907121
Malchow, Berend; Hasan, Alkomiet; Fusar-Poli, Paolo; Schmitt, Andrea; Falkai, Peter; Wobrock, Thomas
The hierarchically organized human brain is viewed as a prime example of a massively parallel, adaptive information processing and process control system. A brief overview of the human brain is provided for computer architects, in hopes that the principles of massive parallelism, dense connectivity and self-organization of assemblies of processing elements will prove relevant to the design of fifth generation VLSI computing networks. 6 references.
The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field. PMID:14509213
Frackowiak, R S
For decades, it was believed that the adult brain was a quiescent organ unable to produce new neurons. At the beginning of the1960's, this dogma was challenged by a small group of neuroscientists. To date, it is well-known that new neurons are generated in the adult brain throughout life. Adult neurogenesis is primary confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone of the dentate gyrus within the hippocampus. In both the human and the rodent brain, the primary progenitor of adult SVZ is a subpopulation of astrocytes that have stem-cell-like features. The human SVZ possesses a peculiar cell composition and displays important organizational differences when compared to the SVZ of other mammals. Some evidence suggests that the human SVZ may be not only an endogenous source of neural precursor cells for brain repair, but also a source of brain tumors. In this review, we described the cytoarchitecture and cellular composition of the SVZ in the adult human brain. We also discussed some clinical implications of SVZ, such as: stem-cell-based therapies against neurodegenerative diseases and its potential as a source of malignant cells. Understanding the biology of human SVZ and its neural progenitors is one of the crucial steps to develop novel therapies against neurological diseases in humans.
Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD) response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course). Knowledge of the neural signal is critical if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by non-invasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential applications ranging from general cognitive studies to assessment of neuropathologies.
Tyler, Christopher W.; Likova, Lora T.
There is a growing interest in exploring the connectivity patterns of the human brain. Specifically, the utility of noninvasive neuroimaging data and graph theoretical analysis have provided important insights into the anatomical connections and topological pattern of human brain structural networks in vivo. This review focuses on recent methodological and application studies, utilizing graph theoretical approaches, on brain structural networks with structural magnetic resonance imaging (MRI) and diffusion MRI. These studies showed many nonrandom properties of structural brain networks, such as small-worldness, modularity, and highly connected hubs. Importantly, topological organization of the networks shows changes during normal development, aging, and neuropsychiatric diseases. Network structures have also been found to correlate with behavioral or cognitive functions, which imply their associations with functional dynamics. These advances not only help us to understand how the healthy human brain is structurally organized, but also provide a novel insight into the biological mechanisms of brain disorders. Future studies will involve the combination of structural/diffusion MRI and functional MRI, to realize how the structural connectivity patterns of the brain underlie its functional states, and will explore whether graph theoretical analysis of structural brain networks could serve as potential imaging biomarkers for disease diagnosis and treatment. PMID:21861783
Lo, Chun-Yi Zac; He, Yong; Lin, Ching-Po
The human brain exhibits remarkable interindividual variability in cortical architecture. Despite extensive evidence for the behavioral consequences of such anatomical variability in individual cortical regions, it is unclear whether and how different cortical regions covary in morphology. Using a novel approach that combined noninvasive cortical functional mapping with whole-brain voxel-based morphometric analyses, we investigated the anatomical relationship between the functionally mapped visual cortices and other cortical structures in healthy humans. We found a striking anticorrelation between the gray matter volume of primary visual cortex and that of anterior prefrontal cortex, independent from individual differences in overall brain volume. Notably, this negative correlation formed along anatomically separate pathways, as the dorsal and ventral parts of primary visual cortex showed focal anticorrelation with the dorsolateral and ventromedial parts of anterior prefrontal cortex, respectively. Moreover, a similar inverse correlation was found between primary auditory cortex and anterior prefrontal cortex, but no anatomical relationship was observed between other visual cortices and anterior prefrontal cortex. Together, these findings indicate that an anatomical trade-off exists between primary sensory cortices and anterior prefrontal cortex as a possible general principle of human cortical organization. This new discovery challenges the traditional view that the sizes of different brain areas simply scale with overall brain size and suggests the existence of shared genetic or developmental factors that contributes to the formation of anatomically and functionally distant cortical regions. PMID:21715612
Song, Chen; Schwarzkopf, Dietrich Samuel; Kanai, Ryota; Rees, Geraint
Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses. PMID:15820887
Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner
Cortical mapping (CSM) studies have shown cortical locations for language function are highly variable from one subject to the next. If individual variation can be normalized, patterns of language organization may emerge that were heretofore hidden. In order to uncover these patterns, computer-aided spatial normalization to a common atlas is required. Our goal was to determine a methodology by which spatial normalization methods could be evaluated and compared. We developed key metrics to measure accuracy of a surface-based (Caret) and volume-based (SPM2) method. We specified that the optimal method would i) minimize variation as measured by spread reduction between CSM language sites across subjects while also ii) preserving anatomical localization of all CSM sites. Eleven subject's structural MR image sets and corresponding CSM site coordinates were registered to the colin27 human brain atlas using each method. Local analysis showed that mapping error rates were highest in morphological regions with the greatest difference between source and target. Also, SPM2 mapped significantly less type 2 errors. Although our experiment did not show statistically significant global differences between the methods, our methodology provided valuable insights into the pros and cons of each method. PMID:17281455
Smith, Veronica; Shapiro, Linda; Hanlon, Donna; Martin, Richard; Brinkley, James; Poliakov, Andrew; Ojemann, George; Corina, David
Comparative studies of the brain in mammals suggest that there are general architectural principles governing its growth and evolutionary development. We are beginning to understand the geometric, biophysical and energy constraints that have governed the evolution and functional organization of the brain and its underlying neuronal network. The object of this review is to present current perspectives on primate brain evolution, especially in humans, and to examine some hypothetical organizing principles that underlie the brain's complex organization. Some of the design principles and operational modes that underlie the information processing capacity of the cerebral cortex in primates will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains, then otherwise would have been possible. In view of the central importance placed on brain evolution in explaining the success of our own species, one may wonder whether there are physical limits that constrain its processing power and evolutionary potential. It will be argued that at a brain size of about 3500 cm3, corresponding to a brain volume two to three times that of modern man, the brain seems to reach its maximum processing capacity. The larger the brain grows beyond this critical size, the less efficient it will become, thus limiting any improvement in cognitive power.
Hofman, Michel A.
As a rule the pterygopalatine ganglion (PPG) is considered to be a single structure of the parasympathetic nervous system, associated with the maxillary nerve in the pterygopalatine fossa (PPF). A few structural studies in humans are available in the indexed references. We designed the present study of the PPG in order to provide evidence of possible variations in morphological patterns of the PPG. We performed dissections of the PPF on 20 human adult heads, using different approaches. The dissected specimens were stained with hematoxylin-eosin and silver (Bielschowsky) or prepared for immunohistochemistry for synaptophisin and neurofilament. Four morphological types of the PPG were defined macroscopically: A (10%): partitioned PPG, the upper partition receiving the vidian nerve; B (55%): single, the upper part (base) receiving the vidian nerve; C (15%): single, but the vidian nerve reaches the lower part (tip) of the ganglion; D (20%): partitioned, the lower partition receiving the vidian nerve. We propose that it may be inappropriate to invariably regard the PPG as a single morphological structure. From individual to individual the PPG may present either as a single ganglion or as a partitioned one, with distinct superior and inferior components. Nevertheless, the presence of the dispersed pterygopalatine microganglia (DPPG) evidenced by histochemistry and immunohistochemistry serves to complete an individually variable morphological pattern of a structure usually described as single. The individual variation may be the reason for failures in ablation procedures of the PPG; partitions of the PPG and/or the DPPG may functionally correlate with specific territories and targets and further tracing studies may be helpful in validating or invalidating this theory. PMID:19124232
Rusu, M C; Pop, F; Curc?, G C; Podoleanu, L; Voinea, L M
Brain structure varies between people in a markedly organized fashion. Communities of brain regions co-vary in their morphological properties. For example, cortical thickness in one region influences the thickness of structurally and functionally connected regions. Such networks of structural co-variance partially recapitulate the functional networks of healthy individuals and the foci of grey matter loss in neurodegenerative disease. This architecture is genetically heritable, is associated with behavioural and cognitive abilities and is changed systematically across the lifespan. The biological meaning of this structural co-variance remains controversial, but it appears to reflect developmental coordination or synchronized maturation between areas of the brain. This Review discusses the state of current research into brain structural co-variance, its underlying mechanisms and its potential value in the understanding of various neurological and psychiatric conditions.
Alexander-Bloch, Aaron; Giedd, Jay N.; Bullmore, Ed
Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind–brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind–brain mechanisms.
Bassett, Danielle S.; Gazzaniga, Michael S.
The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth. PMID:16568243
Talos, I-F; Mian, A Z; Zou, K H; Hsu, L; Goldberg-Zimring, D; Haker, S; Bhagwat, J G; Mulkern, R V
Candida albicans is an opportunistic pathogen, which primarily affects neonates and immunocompromised individuals. The pathogen can invade the central nervous system, resulting in meningitis. At present, the pathogenesis of C. albicans meningitis is unclear. We used an in vitro model of the human blood-brain barrier to investigate the interaction(s) of C. albicans with human brain microvascular endothelial cells (BMEC). Binding of C. albicans to human BMEC was time and inoculum dependent. Invasion of C. albicans into human BMEC was demonstrated by using an enzyme-linked immunosorbent assay based on fluorescent staining of C. albicans with calcoflour. In contrast, avirulent Candida mutant strains and nonpathogenic yeast Saccharomyces cerevisiae were not able to bind and invade human BMEC. Morphological studies revealed that on association with human BMEC, C. albicans formed germ tubes and was able to bud intracellularly. Transmission electron microscopy showed various stages of C. albicans interactions with human BMEC, e.g., pseudopod-like structures on human BMEC membrane and intracellular vacuole-like structures retaining C. albicans. Of interest, C. albicans was able to bud and develop pseudohyphae inside human BMEC without apparent morphological changes of the host cells. In addition, C. albicans penetrates through human BMEC monolayers without a detectable change in transendothelial electrical resistance and inulin permeability. This is the first demonstration that C. albicans is able to adhere, invade, and transcytose across human BMEC without affecting monolayer integrity. A complete understanding of the interaction(s) of C. albicans with human BMEC should contribute to the understanding of the pathogenic mechanism(s) of C. albicans meningitis.
Jong, Ambrose Y.; Stins, Monique F.; Huang, Sheng-He; Chen, Steven H. M.; Kim, Kwang Sik
Modularity, presumably shaped by evolutionary constraints, underlies the functionality of most complex networks ranged from social to biological networks. However, it remains largely unknown in human cortical networks. In a previous study, we demonstrated a network of correlations of cortical thickness among specific cortical areas and speculated that these correlations reflected an underlying structural connectivity among those brain regions. Here, we further investigated the intrinsic modular architecture of the human brain network derived from cortical thickness measurement. Modules were defined as groups of cortical regions that are connected morphologically to achieve the maximum network modularity. We show that the human cortical network is organized into 6 topological modules that closely overlap known functional domains such as auditory/language, strategic/executive, sensorimotor, visual, and mnemonic processing. The identified structure-based modular architecture may provide new insights into the functionality of cortical regions and connections between structural brain modules. This study provides the first report of modular architecture of the structural network in the human brain using cortical thickness measurements.
Chen, Zhang J.; He, Yong; Rosa-Neto, Pedro; Germann, Jurgen
Modularity, presumably shaped by evolutionary constraints, underlies the functionality of most complex networks ranged from social to biological networks. However, it remains largely unknown in human cortical networks. In a previous study, we demonstrated a network of correlations of cortical thickness among specific cortical areas and speculated that these correlations reflected an underlying structural connectivity among those brain regions. Here, we further investigated the intrinsic modular architecture of the human brain network derived from cortical thickness measurement. Modules were defined as groups of cortical regions that are connected morphologically to achieve the maximum network modularity. We show that the human cortical network is organized into 6 topological modules that closely overlap known functional domains such as auditory/language, strategic/executive, sensorimotor, visual, and mnemonic processing. The identified structure-based modular architecture may provide new insights into the functionality of cortical regions and connections between structural brain modules. This study provides the first report of modular architecture of the structural network in the human brain using cortical thickness measurements. PMID:18267952
Chen, Zhang J; He, Yong; Rosa-Neto, Pedro; Germann, Jurgen; Evans, Alan C
The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/). PMID:23861951
Xia, Mingrui; Wang, Jinhui; He, Yong
Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.
Byne, William; Haroutunian, Vahram; Garcia-Villanueva, Mercedes; Rabano, Alberto; Garcia-Amado, Maria; Prensa, Lucia; Gimenez-Amaya, Jose Manuel
Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880
Alelú-Paz, Raúl; Iturrieta-Zuazo, Ignacio; Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel
"Contre-coup" lesions occurring particularly in the frontal and temporal lobes following head injury have been claimed to be caused by sudden negative pressure transients, as part of the "contre-coup" end pressures occurring in the brain tissue at an occipital impact. With a new experimental model such impact acceleration pressure (near-1 atm) could be generated in the rabbit brain through a parietal opening. Resulting morphological changes were evaluated with various microscopical methods, including Evan's blue-albumin technique for observations on vascular permeability changes. Regardless of the magnitude of the negative pressure transients no changes characteristic of "contre-coup" lesions were seen in temporal lobes, i.e. in areas where preparative artefacts are absent in control animals. Therefore such negative pressure transients per se do not appear to be of major importance for the development of contre-coup lesions. However, vascular permeability changes were frequently observed in the brain stem and upper cervical cord and are presumably related to the flow of tissue in the cranio-spinal junction. PMID:1155026
Stålhammar, D; Olsson, Y
There is no consensus as to whether, and if so, in which regard and to what extent science and religion is needed for human survival. Here a circumscribed domain is taken up: the sovereignty and sufficiency of the human brain in this context. Several of its shortcomings are pointed out. Religion and other aspects of culture are needed for remedial…
Reich, K. Helmut
Sepiapterin reductase (SPR) is the enzyme that catalyzes the final step of the synthesis of tetrahydrobiopterin (BH4), the cofactor for phenylalanine hydroxylase, tyrosine hydroxylase (TH), tryptophan hydroxylase, and nitric oxide synthase (NOS). Although SPR is essential for synthesizing BH4, the distribution of SPR in the human brain has not yet been clarified. In the present study, we purified recombinant human
Keiko Ikemoto; Takahiro Suzuki; Hiroshi Ichinose; Tamae Ohye; Akiyoshi Nishimura; Katsuji Nishi; Ikuko Nagatsu; Toshiharu Nagatsu
Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. PMID:22579279
Tyler-Smith, Chris; Xue, Yali
In this report, we review two cases of brain infection due to Dialister pneumosintes in previously healthy patients. The bacterium was isolated from the first patient by blood culture and directly from a brain abscess in the second patient. In both cases, the infection was suspected to be of nasopharyngeal or dental origin. The patients had favorable outcomes following surgical debridement and antibiotic treatment. After in vitro amplification and partial sequencing of the 16S rRNA gene, two strains were classified as D. pneumosintes. However, traditional biochemical tests were not sufficient to identify the bacteria. In addition to causing periodontal and opportunistic infections, D. pneumosintes, contained in mixed flora, may behave as a clinically important pathogen, especially in the brain. In addition to phenotypic characterization, 16S rRNA partial sequencing was used to identify D. pneumosintes definitively.
Rousee, J. M.; Bermond, D.; Piemont, Y.; Tournoud, C.; Heller, R.; Kehrli, P.; Harlay, M. L.; Monteil, H.; Jaulhac, B.
Previous research has identified morphological differences between the brains of Neanderthals and anatomically modern humans (AMHs). However, studies using endocasts or the cranium itself are limited to investigating external surface features and the overall size and shape of the brain. A complementary approach uses comparative primate data to estimate the size of internal brain areas. Previous attempts to do this have generally assumed that identical total brain volumes imply identical internal organization. Here, we argue that, in the case of Neanderthals and AMHs, differences in the size of the body and visual system imply differences in organization between the same-sized brains of these two taxa. We show that Neanderthals had significantly larger visual systems than contemporary AMHs (indexed by orbital volume) and that when this, along with their greater body mass, is taken into account, Neanderthals have significantly smaller adjusted endocranial capacities than contemporary AMHs. We discuss possible implications of differing brain organization in terms of social cognition, and consider these in the context of differing abilities to cope with fluctuating resources and cultural maintenance.
Pearce, Eiluned; Stringer, Chris; Dunbar, R. I. M.
The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed. PMID:23973007
Buchweitz, Augusto; Prat, Chantel
The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.
Buchweitz, Augusto; Prat, Chantel
Based on a complexity analysis of mutual information transmission of EEG developed by us [Xu J, Liu Z, Liu R, Yang Q (1997) Physica D 106: 363-374], dynamic processes of the complexity of mutual information transmission in human brains were studied. To diminish possible problems due to coarse graining preprocessing, some new measures of complexity were used. The results show that, just before and after generalized seizures, the complexities of almost all information transmission between different brain areas drop significantly; there is also a temporary decrease of complexity when subjects shift their attention. The above facts suggest that there is a transient decrease of information transmission complexity when brain state changes occur suddenly. Mental arithmetic tasks activate the left temporal lobe to exchange more information with other brain areas. The results hint that the methods used here might be an approach to observe quick processes in the living brain. PMID:11039700
Chen, F; Xu, J; Gu, F; Yu, X; Meng, X; Qiu, Z
The flow of information from sensory stimuli to motor responses in the human brain can be flexibly re-routed depending on task demands. However, it has remained unclear which sequence of processes is involved in preparing the brain for an upcoming task. Here, we used a combination of fMRI and multivariate pattern classification to decompose the information flow in a task-switching
Stefan Bode; John-Dylan Haynes
New neurons are continuously generated in certain regions of the adult brain. Studies in rodents have shown that new neurons are generated from self-renewing multipotent neural stem cells. Here we demonstrate that both the lateral ventricle wall and the hippocampus of the adult human brain harbor self-renewing cells capable of generating neurons, astrocytes, and oligodendrocytes in vitro, i.e., bona fide
Clas B. Johansson; Mikael Svensson; Lars Wallstedt; Ann Marie Janson; Jonas Frisén
Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/. PMID:20176931
Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian; Gohel, Suril; Kelly, Clare; Smith, Steve M; Beckmann, Christian F; Adelstein, Jonathan S; Buckner, Randy L; Colcombe, Stan; Dogonowski, Anne-Marie; Ernst, Monique; Fair, Damien; Hampson, Michelle; Hoptman, Matthew J; Hyde, James S; Kiviniemi, Vesa J; Kötter, Rolf; Li, Shi-Jiang; Lin, Ching-Po; Lowe, Mark J; Mackay, Clare; Madden, David J; Madsen, Kristoffer H; Margulies, Daniel S; Mayberg, Helen S; McMahon, Katie; Monk, Christopher S; Mostofsky, Stewart H; Nagel, Bonnie J; Pekar, James J; Peltier, Scott J; Petersen, Steven E; Riedl, Valentin; Rombouts, Serge A R B; Rypma, Bart; Schlaggar, Bradley L; Schmidt, Sein; Seidler, Rachael D; Siegle, Greg J; Sorg, Christian; Teng, Gao-Jun; Veijola, Juha; Villringer, Arno; Walter, Martin; Wang, Lihong; Weng, Xu-Chu; Whitfield-Gabrieli, Susan; Williamson, Peter; Windischberger, Christian; Zang, Yu-Feng; Zhang, Hong-Ying; Castellanos, F Xavier; Milham, Michael P
The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral vasculature has allowed measurements of regional cerebral blood volume (rCBV), which are activity dependent. Subsequent investigations linked the MR relaxation properties of brain tissue to blood oxygenation levels which are also modulated by consumption and blood flow (rCBF). These methods have allowed mapping of brain activity in human visual and motor cortex as well as in areas of the frontal lobe involved in language. The methods have high enough spatial and temporal sensitivity to be used in individual subjects. MR spectroscopy of proton and carbon-13 nuclei has been used to measure rates of glucose transport and metabolism in the human brain. The steady-state measurements of brain glucose concentrations can be used to monitor the glycolytic flux, whereas subsequent glucose metabolism--i.e., the flux into the cerebral glutamate pool--can be used to measure tricarboxylic acid cycle flux. Under visual stimulation the concentration of lactate in the visual cortex has been shown to increase by MR spectroscopy. This increase is compatible with an increase of anaerobic glycolysis under these conditions as earlier proposed from positron emission tomography studies. It is shown how MR spectroscopy can extend this understanding of brain metabolism. Images Fig. 1 Fig. 2 Fig. 3
Shulman, R G; Blamire, A M; Rothman, D L; McCarthy, G
We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable (3H)cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific (3H)cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with (3H)cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species.
Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.
Recent work regarding the analysis of brain imaging data has focused on examining functional and effective connectivity of the brain. We develop a novel descriptive and inferential method to analyze the connectivity of the human brain using functional MRI (fMRI). We assess the relationship between pairs of distinct brain regions by comparing expected joint and marginal probabilities of elevated activity of voxel pairs through a Bayesian paradigm, which allows for the incorporation of previously known anatomical and functional information. We define the relationship between two distinct brain regions by measures of functional connectivity and ascendancy. After assessing the relationship between all pairs of brain voxels, we are able to construct hierarchical functional networks from any given brain region and assess significant functional connectivity and ascendancy in these networks. We illustrate the use of our connectivity analysis using data from an fMRI study of social cooperation among women who played an iterated "Prisoner's Dilemma" game. Our analysis reveals a functional network that includes the amygdala, anterior insula cortex, and anterior cingulate cortex, and another network that includes the ventral striatum, orbitofrontal cortex, and anterior insula. Our method can be used to develop causal brain networks for use with structural equation modeling and dynamic causal models. PMID:16092131
Patel, Rajan S; Bowman, F Dubois; Rilling, James K
Adult mandibles of 317 modern humans and 91 great apes were selected that showed no pathology. Adult mandibles of Pan troglodytes troglodytes, Pongo pygmaeus pygmaeus and Gorilla gorilla gorilla and from 2 modern human populations (Zulu and Europeans from Spitalfields) were reliably sexed. Thirteen measurements were defined and included mandibular height, length and breadth in representative positions. Univariate statistical techniques and multivariate (principal component analysis and discriminant analysis) statistical techniques were used to investigate interspecific variability and sexual dimorphism in human and great ape mandibles, and intraspecific variability among the modern human mandibles. Analysis of interspecific differences revealed some pairs of variables with a tight linear relationship and others where Homo and the great apes pulled apart from one another due to shape differences. Homo and Pan are least sexually dimorphic in the mandible, Pan less so than Homo sapiens, but both the magnitude of sexual dimorphism and the distribution of sexually dimorphic measurements varied both among and between modern humans and great apes. Intraspecific variation among the 10 populations of modern humans was less than that generally reported in studies of crania (74.3% of mandibles were correctly classified into 1 of 10 populations using discriminant functions based on 13 variables as compared with 93% of crania from 17 populations based on 70 variables in one extensive study of crania). A subrecent European population (Poundbury) emerged as more different from a recent European population (Spitalfields) than other more diverse modern populations were from each other, suggesting considerable morphological plasticity in the mandible through time. This study forms a sound basis on which to explore mandibular variation in Neanderthals, early Homo sapiens and other more ancient fossil hominids.
HUMPHREY, L. T.; DEAN, M. C.; STRINGER, C. B.
Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109–110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.
Conturo, Thomas E.; Lori, Nicolas F.; Cull, Thomas S.; Akbudak, Erbil; Snyder, Abraham Z.; Shimony, Joshua S.; McKinstry, Robert C.; Burton, Harold; Raichle, Marcus E.
When defining an MRI protocol, brain researchers need to set multiple interdependent parameters that define repetition time (TR), voxel size, field-of-view (FOV), etc. Typically, researchers aim to image the full brain, making the expected FOV an important parameter to consider. Especially in 2D-EPI sequences, non-wasteful FOV settings are important to achieve the best temporal and spatial resolution. In practice, however, imperfect FOV size estimation often results in partial brain coverage for a significant number of participants per study, or, alternatively, an unnecessarily large voxel-size or number of slices to guarantee full brain coverage. To provide normative FOV guidelines we estimated population distributions of brain size in the x-, y-, and z-direction using data from 14,781 individuals. Our results indicated that 11mm in the z-direction differentiate between obtaining full brain coverage for 90% vs. 99.9% of participants. Importantly, we observed that rotating the FOV to optimally cover the brain, and thus minimize the number of slices needed, effectively reduces the required inferior-superior FOV size by ~5%. For a typical adult imaging study, 99.9% of the population can be imaged with full brain coverage when using an inferior-superior FOV of 142mm, assuming optimal slice orientation and minimal within-scan head motion. By providing population distributions for brain size in the x-, y-, and z-direction we improve the potential for obtaining full brain coverage, especially in 2D-EPI sequences used in most functional and diffusion MRI studies. We further enable optimization of related imaging parameters including the number of slices, TR and total acquisition time. PMID:24747737
Mennes, Maarten; Jenkinson, Mark; Valabregue, Romain; Buitelaar, Jan K; Beckmann, Christian; Smith, Stephen
1. The distribution of adenosine triphosphatase was studied in morphologically characterized subcellular fractions of guinea-pig brain. The conditions of homogenization were selected so as to favour the survival of nerve endings as organized structures. 2. A fraction consisting mainly of the external membranes of nerve endings was rich in a ouabain-sensitive Na+–K+-stimulated adenosine triphosphatase which closely resembled that present in the classical microsomal fraction studied by other workers, but which showed a higher specific activity. 3. A dinitrophenol-stimulated adenosine triphosphatase was located in the nerve-ending mitochondria. 4. The synaptic-vesicle fraction contained a small amount of adenosine triphosphatase that differed in its response to several ions and other compounds from the membrane, myelin and mitochondrial fractions, indicating freedom from contamination by these elements. ImagesPLATE 1PLATE 2
Hosie, R. Jeanette A.
Despite the fact that several theories link cortical development and function to the development of white matter and its geometrical structure, the relationship between gray and white matter morphology has not been widely researched. In this paper, we propose a novel framework for investigating this relationship. Given a set of fiber tracts which connect to a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. The distributions of these scalar values are then linked via Mutual Information, which results in a quantitative marker that can be used in the study of normal and pathological brain structure and development. We apply this framework to a population study on autism spectrum disorder in children.
Savadjiev, Peter; Rathi, Yogesh; Bouix, Sylvain; Smith, Alex R.; Schultz, Robert T.; Verma, Ragini; Westin, Carl-Fredrik
The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells.
Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Havard K.; Nygard, Stale; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.
Frequency-modulation is a ubiquitous sound feature present in communicative sounds of various animal species and humans. Functional imaging of the human auditory system has seen remarkable advances in the last two decades and studies pertaining to frequency-modulation have centered around two major questions: a) are there dedicated feature-detectors encoding frequency-modulation in the brain and b) is there concurrent representation with amplitude-modulation, another temporal sound feature? In this review, we first describe how these two questions are motivated by psychophysical studies and neurophysiology in animal models. We then review how human non-invasive neuroimaging studies have furthered our understanding of the representation of frequency-modulated sounds in the brain. Finally, we conclude with some suggestions on how human neuroimaging could be used in future studies to address currently still open questions on this fundamental sound feature. This article is part of a Special Issue entitled Human Auditory Neuroimaging. PMID:23933098
Altmann, Christian F; Gaese, Bernhard H
Background Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and ?-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases.
Toth, Andrea E.; Walter, Fruzsina R.; Bocsik, Alexandra; Santha, Petra; Veszelka, Szilvia; Nagy, Lajos; Puskas, Laszlo G.; Couraud, Pierre-Olivier; Takata, Fuyuko; Dohgu, Shinya; Kataoka, Yasufumi; Deli, Maria A.
Thrombin, a serine protease that regulates hemostasis, has been shown to stimulate the formation of cGMP in murine neuroblastoma cells. The nervous system in vivo thus may be postulated to respond to this blood-borne factor after it breaches the blood-brain barrier, as in trauma. Human alpha-thrombin was radiolabeled with 125I and shown to bind rapidly, reversibly, and with high affinity to human brain and spinal cord. These findings indicate the presence of specific thrombin-binding sites in nervous tissue and may have important clinical implications.
McKinney, M.; Snider, R.M.; Richelson, E.
In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brain regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. 109 references.
The complex functional morphologic characteristics of the knee are of ancient origin. The multiple asymmetries of anatomy can be traced back more than 300 million years to the pelvic appendages of Sarcoptorigian lobe-finned fish. The knee functions as a biologic transmission with ligaments acting as sensate linkages and the menisci acting as sensate, mobile bearings. Cine-computed tomography and magnetic resonance imaging studies of intact knees from cadavers reveal a combined rolling and gliding motion, with posterior displacement of the femorotibial contact point with increasing flexion. The posterior displacement of the femorotibial contact point is greater in the lateral compartment by approximately a factor of two. The anatomy of the lateral compartment, including the inferior sloping of the posterior tibial plateau, reflects and accommodates this greater motion. This asymmetry of kinematics between the medial and lateral compartment, an established characteristic of human and many other extant mammalian knees, results in an internal rotation of the tibia relative to femur with increasing flexion. By taking into account the complexities of functional morphologic features of the knee, the design of joint replacements and bracing systems may be improved. PMID:12771813
Dye, Scott F
On admission to the hospital, a splenectomized man was found to have 85% of his erythrocytes parasitized by Babesia microti. His extensive parasitemia allowed for direct study of the morphology and ultrastructure of this organism as it appears in human infection; the need for animal inoculation and rescue techniques was thus eliminated. Positive characteristics (other than the tetrad form) that are diagnostic for babesiosis were identified. By transmission and scanning electron microscopy, parasite-induced changes in the erythrocyte membrane were observed; these alterations may explain the hemolysis seen in babesiosis. Factors that may have allowed the patient to sustain such high-level parasitemia are considered. The experience with this patient confirms that exchange transfusion is a reliable, rapid method for reduction of the parasite load in serious infection with B microti. PMID:6684141
Sun, T; Tenenbaum, M J; Greenspan, J; Teichberg, S; Wang, R T; Degnan, T; Kaplan, M H
Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed. PMID:23256049
Chen, Bin; Moreland, John; Zhang, Jingyu
The concept of attention as central to human performance extends back to the start of experimental psychology, yet even a few years ago, it would not have been possible to outline in even a preliminary form a functional anatomy of the human attentional sy...
M. I. Posner S. E. Petersen
Reinforcements and punishments facilitate adaptive behavior in diverse domains ranging from perception to social interactions. A conventional approach to understanding the corresponding neural substrates focuses on the basal ganglia and its dopaminergic projections. Here, we show that reinforcement and punishment signals are surprisingly ubiquitous in the gray matter of nearly every subdivision of the human brain. Humans played either matching-pennies or rock-paper-scissors games against computerized opponents while being scanned using fMRI. Multivoxel pattern analysis was used to decode previous choices and their outcomes, and to predict upcoming choices. Whereas choices were decodable from a confined set of brain structures, their outcomes were decodable from nearly all cortical and subcortical structures. In addition, signals related to both reinforcements and punishments were recovered reliably in many areas and displayed patterns not consistent with salience-based explanations. Thus, reinforcement and punishment might play global modulatory roles in the entire brain. PMID:21982377
Vickery, Timothy J; Chun, Marvin M; Lee, Daeyeol
The majority of studies of frontal bone morphology in paleoanthropology have analyzed the frontal squama and the browridge as a single unit, mixing information from different functional elements. Taking into account that the bulging of the frontal bone is often described as a species-specific trait of Homo sapiens, in this article we analyze variation in the midsagittal profile of the genus Homo, focusing on the frontal squama alone, using landmark-based superimpositions and principal components analysis. Our results demonstrate that anatomically modern humans are definitely separated from extinct human taxa on the basis of frontal bulging. However, there is minor overlap among these groups, indicating that it is necessary to exercise caution when using this trait alone to make taxonomic inferences on individual specimens. Early modern humans do not show differences with recent modern humans, and "transitional" individuals such as Jebel Irhoud 1, Maba, and Florisbad, show modern-like frontal squama morphology. The bulging of the frontal squama in modern humans may represent a structural consequence of more general cranial changes, or it could be a response to changes in the morphology of the underlying prefrontal brain elements. A subtle difference between Neandertals and the Afro-European Middle Pleistocene Homo sample is associated with flattening at bregma in the former group, a result that merits further investigation. PMID:23292748
Bruner, Emiliano; Athreya, Sheela; de la Cuétara, José Manuel; Marks, Tarah
The purpose of this study is to investigate whether specific patterns of correlation exist in diffusion tensor imaging (DTI) parameters across different white matter tracts in the normal human brain, and whether the relative strengths of these putative microstructural correlations might reflect phylogenetic and functional similarities between tracts. We performed quantitative DTI fiber tracking on 44 healthy adult volunteers to
Michael Wahl; Yi-Ou Li; Joshua Ng; Sara C. LaHue; Shelly R. Cooper; Elliott H. Sherr; Pratik Mukherjee
The concentration of manganese per gram dry tissue weight was determined in samples from 39 areas of 8 normal human brains. Manganese was shown to be unevenly distributed with the largest concentrations in the pineal gland and the olfactory bulb. The gray matter yielded a higher content of manganese than the white matter. Significant differences between individuals were found for
Ernesto Bonilla; Enrique Salazar; Jose Joaquin Villasmil; Ruddy Villalobos
We have found marked anatomical asymmetries between the upper surfaces of the human right and left temporal lobes. The planum temporale (the area behind Heschl's gyrus) is larger on the left in 65 percent of brains; on the right it is larger in only 11 percent. The left planum is on the average one-third longer than the right planum. This
Norman Geschwind; Walter Levitsky
The aim of this project was to provide students with plastinated specimens showing the three-dimensional features and contents of the human brain ventricular cavities. To fill the cavities, six cannulas were introduced through the cerebral cortex into the horns of both lateral ventricles, and a seventh one between the pons and the cerebellum into the fourth ventricle. Ventricles were filled
Gilles Grondin; Atchara Sianothai; Regis Olry
Functional magnetic resonance imaging (FMRI) can provide detailed images of human brain that reflect localized changes in cerebral blood flow and oxygenation induced by sensory, motor, or cognitive tasks. This review presents methods for gradient-recalled echo-planar functional magnetic resonance imaging (FMRI). Also included is a discussion of the hypothesized basis of FMRI, imaging hardware, a unique visual stimulation apparatus, image
Edgar A. DeYoe; Peter Bandettini; Jay Neitz; David Miller; Paula Winans
I go deep into the biology of the human organism to argue that the psychological features and functions of persons are realized by cellular and molecular parallel distributed processing networks dispersed throughout the whole body. Persons supervene on the computational processes of nervous, endocrine, immune, and genetic networks. Persons do not go with brains.
I go deep into the biology of the human organism to argue that the psychological features and functions of persons are realized by cellular and molecular parallel distributed processing networks dispersed throughout the whole body. Persons supervene on the compu- tational processes of nervous, endocrine, immune, and genetic networks. Persons do not go with brains.
Romantic love has been the source for some of the greatest achievements of mankind throughout the ages. The recent localization of romantic love within subcortico–cortical reward, motivation and emotion systems in the human brain has suggested that love is a goal-directed drive with predictable facilitation effects on cognitive behavior, rather than a pure emotion. Here we show that the subliminal
Francesco Bianchi-Demicheli; Scott T. Grafton; Stephanie Ortigue
Objective. Circulus arteriosus/circle of Willis (CW) is a polygonal anastomotic channel at the base of the brain which unites the internal carotid and vertebrobasilar system. It maintains the steady and constant supply to the brain. The variations of CW are seen often. The Aim of the present work is to find out the percentage of normal pattern of CW, and the frequency of variations of the CW and to study the morphological and morphometric aspects of all components of CW. Methods. Circulus arteriosus of 150 formalin preserved brains were dissected. Dimensions of all the components forming circles were measured. Variations of all the segments were noted and well photographed. The variations such as aplasia, hypoplasia, duplication, fenestrations, and difference in dimensions with opposite segments were noted. The data collected in the study was analyzed. Results. Twenty-one different types of CW were found in the present study. Normal and complete CW was found in 60%. CW with gross morphological variations was seen in 40%. Maximum variations were seen in the PCoA followed by the ACoA in 50% and 40%, respectively. Conclusion. As it confirms high percentage of variations, all surgical interventions should be preceded by angiography. Awareness of these anatomical variations is important in neurovascular procedures.
Gunnal, S. A.; Farooqui, M. S.; Wabale, R. N.
A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.
Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.
Theory predicts a close structural relation of formal languages with natural languages. Both share the aspect of an underlying grammar which either generates (hierarchically) structured expressions or allows us to decide whether a sentence is syntactically correct or not. The advantage of rule-based communication is commonly believed to be its efficiency and effectiveness. A particularly important class of formal languages are those underlying the mathematical syntax. Here we provide brain-imaging evidence that the syntactic processing of abstract mathematical formulae, written in a first order language, is, indeed efficient and effective as a rule-based generation and decision process. However, it is remarkable, that the neural network involved, consisting of intraparietal and prefrontal regions, only involves Broca's area in a surprisingly selective way. This seems to imply that despite structural analogies of common and current formal languages, at the neural level, mathematics and natural language are processed differently, in principal.
Friedrich, Roland; Friederici, Angela D.
A unique feature of Citrobacter koseri is the extremely high propensity to initiate brain abscesses during neonatal meningitis. Previous clinical reports and studies on infant rats have documented many Citrobacter-filled macrophages within the ventricles and brain abscesses. It has been hypothesized that intracellular survival and replication within macrophages may be a mechanism by which C. koseri subverts the host response and elicits chronic infection, resulting in brain abscess formation. In this study, we showed that C. koseri causes meningitis and brain abscesses in the neonatal rat model, and we utilized histology and magnetic resonance imaging technology to visualize brain abscess formation. Histology and electron microscopy (EM) revealed that macrophages (and not fibroblasts, astrocytes, oligodendrocytes, or neurons) were the primary target for long-term C. koseri infection. To better understand C. koseri pathogenesis, we have characterized the interactions of C. koseri with human macrophages. We found that C. koseri survives and replicates within macrophages in vitro and that uptake of C. koseri increases in the presence of human pooled serum in a dose-dependent manner. EM studies lend support to the hypothesis that C. koseri uses morphologically different methods of uptake to enter macrophages. FcgammaRI blocking experiments show that this receptor primarily facilitates the entry of opsonized C. koseri into macrophages. Further, confocal fluorescence microscopy demonstrates that C. koseri survives phagolysosomal fusion and that more than 90% of intracellular C. koseri organisms are colocalized within phagolysosomes. The ability of C. koseri to survive phagolysosome fusion and replicate within macrophages may contribute to the establishment of chronic central nervous system infection including brain abscesses. PMID:14500508
Townsend, Stacy M; Pollack, Harvey A; Gonzalez-Gomez, Ignacio; Shimada, Hiroyuki; Badger, Julie L
The diagnostic stages of intestinal parasites are differentiated on the basis of specific morphologic features that can be seen microscopically. Although Dientamoeba fragilis is a flagellate, morphologically, it resembles the amebae. Therefore, in this ma...
M. M. Brooke D. M. Melvin
Magnetite has a long and distinguished career as one of the most important minerals in geophysics, as it is responsible for most of the remanent magnetization in marine sediments and the oceanic crust. It may come as a surprise to discover that it also ranks as the third or fourth most diverse mineral product formed biochemically by living organisms, and forms naturally in a variety of human tissues [Kirschvink et al., 1992].Magnetite was discovered in teeth of the Polyplacophora mollusks over 30 years ago, in magnetotactic bacteria nearly 20 years ago, in honey bees and homing pigeons nearly 15 years ago, but only recently in human tissue.
Kirschvink, Joseph L.
Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [11C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([11C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [11C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [11C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (> 250% higher, p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.
Sekine, Yoshimoto; Ouchi, Yasuomi; Sugihara, Genichi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Iwata, Yasuhide; Tsuchiya, Kenji J.; Suda, Shiro; Suzuki, Katsuaki; Kawai, Masayoshi; Takebayashi, Kiyokazu; Yamamoto, Shigeyuki; Matsuzaki, Hideo; Ueki, Takatoshi; Mori, Norio; Gold, Mark S.; Cadet, Jean L.
This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (iv) catheter were exposed to METH (9 mg/kg) at standard (23°C) and warm (29°C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological levels (38–42°C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5°C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na+, K+, Cl?) contents, immunostained for albumin and glial fibrillary acidic protein, and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29°C than 23°C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse.
Sharma, Hari S.; Kiyatkin, Eugene A.
Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta, an antacid, given to one case. The evidence that chromium induced pathological changes in these three brains is circumstantial but shows that chromium can penetrate the human brain. This study indicates that vascular siderosis found in the brains of the majority of middle-aged and elderly humans is not simply an anecdotal pathological curiosity, but that it can serve as a route of entry for toxic products into the brain. Images
Traumatic brain injury (TBI) survivors experience long-term post-traumatic morbidities. In diffuse brain-injured rats, a chronic sensory sensitivity to whisker stimulation models the agitation of TBI survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate post-traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. Here we hypothesize that a temporal sequence of microglial activation states contributes to the circuit pathology responsible for post-traumatic morbidity, and test the hypothesis by examining microglial morphological activation and neuroinflammatory markers for activation states through gene expression and receptor-binding affinity. Adult male, Sprague-Dawley rats were subjected to a single moderate midline fluid percussion injury (FPI) or sham injury. Microglial activation was determined by immunohistochemistry, quantitative real-time PCR and receptor autoradiography in the primary somatosensory barrel field (S1BF) and ventral posterior medial nucleus (VPM) of the thalamus at 7 and 28 days following FPI. Morphological changes indicative of microglial activation, including swollen cell body with thicker, shrunken processes, were evident in S1BF and VPM at 7 and 28 days post-injury. Principally at 7 days post-injury in VPM, general inflammatory gene expression (major histocompatibility complex I, major histocompatibility complex II, translocator protein 18 kDa [TSPO]) is increased above sham level and TSPO gene expression confirmed by receptor autoradiography. Further, CD45, a marker of classical activation, and TGF-?I, an acquired deactivation marker, were elevated significantly above sham at 7 days post-injury. Daily administration of the anti-inflammatory ibuprofen (20mg/kg, i.p.) significantly reduced the expression of these genes. Evidence for alternative activation (arginase 1) was not observed. Thus, these data demonstrate concomitant classical activation and acquired deactivation phenotypes of microglia in diffuse TBI in the absence of overt contusion or cavitation. Anti-inflammatory treatment may further alleviate the neuropathological burden of post-traumatic inflammation. PMID:22960311
Cao, T; Thomas, T C; Ziebell, J M; Pauly, J R; Lifshitz, J
Behavioral categories of functional imaging experiments along with standardized brain coordinates of associated activations were used to develop a method to automate regional behavioral analysis of human brain images. Behavioral and coordinate data were taken from the BrainMap database (http://www.brainmap.org/), which documents over 20 years of published functional brain imaging studies. A brain region of interest (ROI) for behavioral analysis can be defined in functional images, anatomical images or brain atlases, if images are spatially normalized to MNI or Talairach standards. Results of behavioral analysis are presented for each of BrainMap's 51 behavioral sub-domains spanning five behavioral domains (Action, Cognition, Emotion, Interoception, and Perception). For each behavioral sub-domain the fraction of coordinates falling within the ROI was computed and compared with the fraction expected if coordinates for the behavior were not clustered, i.e., uniformly distributed. When the difference between these fractions is large behavioral association is indicated. A z-score ? 3.0 was used to designate statistically significant behavioral association. The left-right symmetry of ~100K activation foci was evaluated by hemisphere, lobe, and by behavioral sub-domain. Results highlighted the classic left-side dominance for language while asymmetry for most sub-domains (~75%) was not statistically significant. Use scenarios were presented for anatomical ROIs from the Harvard-Oxford cortical (HOC) brain atlas, functional ROIs from statistical parametric maps in a TMS-PET study, a task-based fMRI study, and ROIs from the ten “major representative” functional networks in a previously published resting state fMRI study. Statistically significant behavioral findings for these use scenarios were consistent with published behaviors for associated anatomical and functional regions.
Lancaster, Jack L.; Laird, Angela R.; Eickhoff, Simon B.; Martinez, Michael J.; Fox, P. Mickle; Fox, Peter T.
The arterial baroreflex is a key mechanism for the homeostatic control of blood pressure (BP). In animals and humans, psychological stressors suppress the capacity of the arterial baroreflex to control short-term fluctuations in BP, reflected by reduced baroreflex sensitivity (BRS). While animal studies have characterized the brain systems that link stressor processing to BRS suppression, comparable human studies are lacking. Here, we measured beat-to-beat BP and heart rate (HR) in 97 adults who performed a multisource interference task that evoked changes in spontaneous BRS, which were quantified by a validated sequence method. The same 97 participants also performed the task during functional magnetic resonance imaging (fMRI) of brain activity. Across participants, task performance (i) increased BP and HR and (ii) reduced BRS. Analyses of fMRI data further demonstrated that a greater task-evoked reduction in BRS covaried with greater activity in brain systems important for central autonomic and cardiovascular control, particularly the cingulate cortex, insula, amygdala, and midbrain periaqueductal gray (PAG). Moreover, task performance increased the functional connectivity of a discrete area of the anterior insula with both the cingulate cortex and amygdala. In parallel, this same insula area showed increased task-evoked functional connectivity with midbrain PAG and pons. These novel findings provide human evidence for the brain systems presumptively involved in suppressing baroreflex functionality, with relevance for understanding the neurobiological mechanisms of stressor-related cardiovascular reactivity and associated risk for essential hypertension and atherosclerotic heart disease.
Gianaros, Peter J.; Onyewuenyi, Ikechukwu C.; Sheu, Lei K.; Christie, Israel C.; Critchley, Hugo D.
Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.
Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.
The aim of the present work was to study human neural stem\\/progenitor cells (SPC) cultured in vitro and their potential to survive, migrate, and differentiate after transplantation into adult rat brain. SPC were extracted from the brains of nine-week human embryos and were cultured in selective medium for three weeks. Transplantation was with suspensions of cells or whole neurospheres; these
M. A. Aleksandrova; R. A. Poltavtseva; A. V. Revishchin; L. I. Korochkin; G. T. Sukhikh
The membrane-associated drug transporter P-glycoprotein (P-gp) plays an essential role in drug efflux from the brain. Induction of this protein at the blood-brain barrier (BBB) could further affect the ability of a drug to enter the brain. At present, P-gp induction mediated by antiretroviral drugs at the BBB has not been fully investigated. Since P-gp expression is regulated by ligand-activated nuclear receptors, i.e., human pregnane X receptor (hPXR) and human constitutive androstane receptor (hCAR), these receptors could represent potential pathways involved in P-gp induction by antiretroviral drugs. The aims of this study were (i) to determine whether antiretroviral drugs currently used in HIV pharmacotherapy are ligands for hPXR or hCAR and (ii) to examine P-gp function and expression in human brain microvessel endothelial cells treated with antiretroviral drugs identified as ligands of hPXR and/or hCAR. Luciferase reporter gene assays were performed to examine the activation of hPXR and hCAR by antiretroviral drugs. The hCMEC/D3 cell line, which is known to display several morphological and biochemical properties of the BBB in humans, was used to examine P-gp induction following 72 h of exposure to these agents. Amprenavir, atazanavir, darunavir, efavirenz, ritonavir, and lopinavir were found to activate hPXR, whereas abacavir, efavirenz, and nevirapine were found to activate hCAR. P-gp expression and function were significantly induced in hCMEC/D3 cells treated with these drugs at clinical concentrations in plasma. Together, our data suggest that P-gp induction could occur at the BBB during chronic treatment with antiretroviral drugs identified as ligands of hPXR and/or hCAR.
Chan, Gary N. Y.; Patel, Rucha; Cummins, Carolyn L.
A human malignant continuous cell line, named NG97, was recently established in our laboratory. This cell line has been serially subcultured over 100 times in standard culture media presenting no sign of cell senescence. The NG97 cell line has a doubling time of about 24 h. Immunocytochemical analysis of glial markers demonstrated that cells are positive for glial fibrillary acidic protein (GFAP) and S-100 protein, and negative for vimentin. Under phase-contrast microscope, cultures of NG97 showed cells with variable morphological features, such as small rounded cells, fusiform cells (fibroblastic-like cells), and dendritic-like cells. However, at confluence just small rounded and fusiform cells can be observed. At scanning electron microscopy (SEM) small rounded cells showed heterogeneous microextentions, including blebs and filopodia. Dendritic-like cells were flat and presented extensive prolongations, making several contacts with small rounded cells, while fusiform cells presented their surfaces dominated by microvilli.We believe that the knowledge about NG97 cell line may be useful for a deeper understanding of biological and immunological characteristics of gliomas. PMID:15885136
Machado, Camila Ml; Schenka, André; Vassallo, José; Tamashiro, Wirla Msc; Gonçalves, Estela M; Genari, Selma C; Verinaud, Liana
A human malignant continuous cell line, named NG97, was recently established in our laboratory. This cell line has been serially subcultured over 100 times in standard culture media presenting no sign of cell senescence. The NG97 cell line has a doubling time of about 24 h. Immunocytochemical analysis of glial markers demonstrated that cells are positive for glial fibrillary acidic protein (GFAP) and S-100 protein, and negative for vimentin. Under phase-contrast microscope, cultures of NG97 showed cells with variable morphological features, such as small rounded cells, fusiform cells (fibroblastic-like cells), and dendritic-like cells. However, at confluence just small rounded and fusiform cells can be observed. At scanning electron microscopy (SEM) small rounded cells showed heterogeneous microextentions, including blebs and filopodia. Dendritic-like cells were flat and presented extensive prolongations, making several contacts with small rounded cells, while fusiform cells presented their surfaces dominated by microvilli. We believe that the knowledge about NG97 cell line may be useful for a deeper understanding of biological and immunological characteristics of gliomas.
Machado, Camila ML; Schenka, Andre; Vassallo, Jose; Tamashiro, Wirla MSC; Goncalves, Estela M; Genari, Selma C; Verinaud, Liana
The observation of koilocyte-like features in the squamous epithelium of some endometrial adenoacanthomas prompted an investigation into a possible viral aetiology. These changes closely resemble those that occur in the ectocervical mucosa which are accepted as morphological evidence of human papillomavirus (HPV) infection. Sections of 87 hysterectomy specimens removed for endometrial carcinoma over 12 years, together with preoperative curettings, were reviewed for the presence of acanthomatous change and for appearances suggestive of HPV infection. The ages of the women ranged from 36 to 84 years, average age 62.6. Light microscopical examination showed koilocytosis, papillary formations, and intranuclear eosinophilic inclusions of both squamous and glandular epithelium in some tumours. Immunocytochemistry and DNA in situ hybridisation indicated the presence of HPV antigen in squamous and glandular cells, and perinuclear virus particles characteristic of HPV were seen on electron microscopical examination in those cells with nuclear inclusions. HPV probably infects endometrial adenocarcinomas directly from the cervix but it is unlikely that it has an aetiological role. It is possible, however, that in addition to being a "passenger," the virus may stimulate squamous metaplasia in some adenocarcinomas of the endometrium and may also exert some influence on their behaviour. Images
Kealy, W F; Annis, P G; Barry, J A; Hogan, J M
The observation of koilocyte-like features in the squamous epithelium of some endometrial adenoacanthomas prompted an investigation into a possible viral aetiology. These changes closely resemble those that occur in the ectocervical mucosa which are accepted as morphological evidence of human papillomavirus (HPV) infection. Sections of 87 hysterectomy specimens removed for endometrial carcinoma over 12 years, together with preoperative curettings, were reviewed for the presence of acanthomatous change and for appearances suggestive of HPV infection. The ages of the women ranged from 36 to 84 years, average age 62.6. Light microscopical examination showed koilocytosis, papillary formations, and intranuclear eosinophilic inclusions of both squamous and glandular epithelium in some tumours. Immunocytochemistry and DNA in situ hybridisation indicated the presence of HPV antigen in squamous and glandular cells, and perinuclear virus particles characteristic of HPV were seen on electron microscopical examination in those cells with nuclear inclusions. HPV probably infects endometrial adenocarcinomas directly from the cervix but it is unlikely that it has an aetiological role. It is possible, however, that in addition to being a "passenger," the virus may stimulate squamous metaplasia in some adenocarcinomas of the endometrium and may also exert some influence on their behaviour. PMID:2166095
Kealy, W F; Annis, P G; Barry, J A; Hogan, J M
This paper describes a method for subcortical identification and labeling of 3D medical MRI images. Indeed, the ability to identify similarities between the most characteristic subcortical structures such as sulci and gyri is helpful for human brain mapping studies in general and medical diagnosis in particular. However, these structures vary greatly from one individual to another because they have different geometric properties. For this purpose, we have developed an efficient tool that allows a user to start with brain imaging, to segment the border gray/white matter, to simplify the obtained cortex surface, and to describe this shape locally in order to identify homogeneous features. In this paper, a segmentation procedure using geometric curvature properties that provide an efficient discrimination for local shape is implemented on the brain cortical surface. Experimental results demonstrate the effectiveness and the validity of our approach.
Genetic, biochemical, and animal model studies strongly suggest a central role for ?-synuclein in the pathogenesis of Parkinson's disease. ?-synuclein lacks a signal peptide sequence and has thus been considered a cytosolic protein. Recent data has suggested that the protein may be released from cells via a non-classical secretory pathway and may therefore exert paracrine effects in the extracellular environment. However, proof that ?-synuclein is actually secreted into the brain extracellular space in vivo has not been obtained. We developed a novel highly sensitive ELISA in conjugation with an in vivo microdialysis technique to measure ?-synuclein in brain interstitial fluid. We show for the first time that ?-synuclein is readily detected in the interstitial fluid of both ?-synuclein transgenic mice and human patients with traumatic brain injury. Our data suggest that ?-synuclein is physiologically secreted by neurons in vivo. This interstitial fluid pool of the protein may have a role in the propagation of synuclein pathology and progression of Parkinson's disease.
Emmanouilidou, Evangelia; Elenis, Dimitris; Papasilekas, Themis; Stranjalis, Georgios; Gerozissis, Kyriaki; Ioannou, Penelopi C.; Vekrellis, Kostas
Epidemiological studies demonstrate an association between chronic consumption of arsenic contaminated water and cognitive deficits, especially when the exposure takes place during childhood. This study documents structural changes and nitrergic deficits in the striatum of adult female Wistar rats exposed to arsenic in drinking water (3 ppm, approximately 0.4 mg/kg per day) from gestation, throughout lactation and development until the age of 4 months. Kainic acid injected animals (10mg/kg, i.p.) were also analyzed as positive controls of neural cell damage. Morphological characteristics of cells, fiber tracts and axons were analyzed by means of light microscopy as well as immunoreactivity to neuronal nitric oxide synthase (nNOS). As nitrergic markers, nitrite/nitrate concentrations, nNOS levels and expression of nNOS-mRNA were quantified in striatal tissue. Reactive oxygen species (ROS) and lipid peroxidation (LPx) were determined as oxidative stress markers. Arsenic exposure resulted in moderate to severe alterations of thickness, organization, surrounding space and shape of fiber tracts and axons, while cell bodies remained healthy. These anomalies were not accompanied by ROS and/or LPx increases. By contrast, except the expression of nNOS-mRNA, all nitrergic markers including striatal nNOS immunoreactivity presented a significant decrease. These results indicate that arsenic targets the central nitrergic system and disturbs brain structural organization at low exposure levels. PMID:19409443
Ríos, R; Zarazúa, S; Santoyo, M E; Sepúlveda-Saavedra, J; Romero-Díaz, V; Jiménez, V; Pérez-Severiano, F; Vidal-Cantú, G; Delgado, J M; Jiménez-Capdeville, M E
A new effective procedure for purifying of glutamine synthetase (GS, EC 22.214.171.124) from human brain has been developed. The procedure includes homogenization of brain tissue, centrifugation, precipitation with (NH4)2SO4, ion-exchange chromatography on cellulose DE-32 and CM-32, gel-filtration on Sepharose CL-6B and chromatography on AH-Sepharose 4B. On SDS-PAAG electrophoresis purified GS gives a single protein band with a molecular mass of about 44 kDa. Two-dimensional electrophoresis of GS performed according to O'Farrell gives a protein spots multiplet (all the spots corresponding to M(r) approximately 44 kDa and pI 6.7-7.2), presumably as a result of covalent modification of GS subunits. The apparent Km value for L-Glu in the synthetase reaction is 14.3 mM; the Km value for L-Gln in the transferase reaction is 18.1 mM. The pH values of 6-7 and 7.2 were found to be optimal for the transferase and synthase GS activities in the imidazole buffer. The optimal concentrations of Mg2+ ions for the synthetase and transferase activities of GS were 10 and 15-20 mM, respectively; that of Mn2+ ions was 1 mM for the both reactions. Some biochemical properties (isoelectric point, subunit molecular masses, optimal concentrations of metal ions) differ essentially from those of animal GS. Rabbit polyclonal antibodies raised against the human brain GS detect GS in human brain homogenates, but not in rat or bovine brain homogenates. PMID:8555365
Boksha, I S; Tereshkina, E B; Burbaeva, G Sh
Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH) with noxious heat led to activation in different columns of the midbrain periaqueductal gray (PAG). The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by functional MRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM). In a second experiment, we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e., the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.
Ritter, Alexander; Franz, Marcel; Dietrich, Caroline; Miltner, Wolfgang H. R.; Weiss, Thomas
The goal of this study was to address the need for comprehensive reference data regarding maturational and aging effects on regional transverse relaxation rates (R2) of the brain in normal humans. Regional R2s were measured in twenty-five brain structures from a sample of seventy-seven normal volunteers 9 to 85 years of age. The relationships between regional R2 and age were determined using generalized additive models, without the constraint of a specified a priori model. Data analysis demonstrated that the brain tissue R2-age correlations followed various time courses with both linear and non-linear characteristics depending on the particular brain structure. Most anatomical structures studied exhibited non-linear characteristics, including the amygdala, hippocampus, thalamus, globus pallidus, putamen, caudate nucleus, red nucleus, substantia nigra, orbitofrontal white matter and temporal white matter. Linear trends were detected in occipital white matter and in the genu of corpus callosum. These results indicate the complexity of age-related R2 changes in the brain while providing normative reference data that can be utilized in clinical examinations and studies utilizing quantitative transverse relaxation.
Wang, Jianli; Shaffer, Michele L.; Eslinger, Paul J.; Sun, Xiaoyu; Weitekamp, Christopher W.; Patel, Megha M.; Dossick, Deborah; Gill, David J.; Connor, James R.; Yang, Qing X.
Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ?900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553
Hawrylycz, Michael J; Lein, Ed S; Guillozet-Bongaarts, Angela L; Shen, Elaine H; Ng, Lydia; Miller, Jeremy A; van de Lagemaat, Louie N; Smith, Kimberly A; Ebbert, Amanda; Riley, Zackery L; Abajian, Chris; Beckmann, Christian F; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F; Cartagena, Preston M; Chakravarty, M Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A; Daly, Barry David; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A; Faber, Vance; Feng, David; Fowler, David R; Goldy, Jeff; Gregor, Benjamin W; Haradon, Zeb; Haynor, David R; Hohmann, John G; Horvath, Steve; Howard, Robert E; Jeromin, Andreas; Jochim, Jayson M; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T; Lee, Changkyu; Lemon, Tracy A; Li, Ling; Li, Yang; Morris, John A; Overly, Caroline C; Parker, Patrick D; Parry, Sheana E; Reding, Melissa; Royall, Joshua J; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R; Smith, Simon C; Sodt, Andy J; Sunkin, Susan M; Swanson, Beryl E; Vawter, Marquis P; Williams, Derric; Wohnoutka, Paul; Zielke, H Ronald; Geschwind, Daniel H; Hof, Patrick R; Smith, Stephen M; Koch, Christof; Grant, Seth G N; Jones, Allan R
The brain consists of diverse cell types including neurons, astrocytes, oligodendrocytes, and microglia. The isolation of nuclei from these distinct cell populations provides an opportunity to identify cell-type-specific nuclear proteins, histone modifications, and regulation networks that are altered with normal brain aging or neurodegenerative disease. In this study, we used a method by which intact neuronal and non-neuronal nuclei were purified from human post-mortem brain employing a modification of fluorescence activated cell sorting (FACS) termed fluorescence activated nuclei sorting (FANS). An antibody against NeuN, a neuron specific splicing factor, was used to isolate neuronal nuclei. Utilizing mass spectrometry (MS) based label-free quantitative proteomics, we identified 1755 proteins from sorted NeuN-positive and negative nuclear extracts. Approximately 20% of these proteins were significantly enriched or depleted in neuronal versus non-neuronal populations. Immunoblots of primary cultured rat neuron, astrocyte, and oligodendrocyte extracts confirmed that distinct members of the major nucleocytoplasmic structural linkage complex (LINC), nesprin-1 and nesprin-3, were differentially enriched in neurons and astrocytes, respectively. These comparative proteomic data sets also reveal a number of transcription and splicing factors that are selectively enriched in a cell-type-specific manner in human brain. PMID:23768213
Dammer, Eric B; Duong, Duc M; Diner, Ian; Gearing, Marla; Feng, Yue; Lah, James J; Levey, Allan I; Seyfried, Nicholas T
The presence of genetic influences on cognitive performance and brain volume is well established. However, specific genetic determinants of the variance of these quantitative traits are not yet known. Plexins act as receptors for semaphorins and are implicated in axon guidance, which is a key process in brain development. We have previously shown that plexin B3 is a highly potent stimulator of neurite outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits related to human brain development and cerebral connectivity. We identified several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D and V1596E) conserved at the corresponding positions of the orthologs in mouse and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male patients with schizophrenia. Cognitive performance was measured with the vocabulary test (Wortschatztest (WST)), a method to estimate roughly general intelligence (g). Brain morphology was characterized by magnetic resonance imaging. Compared to subjects not carrying the modern, human-specific haplotype A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis (P=0.0004). This effect could be observed in three independent groups (healthy males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037). Additionally, the haplotype A was associated with increased volume of brain white matter that in turn correlated with performance in the vocabulary test. These findings suggest that plexin B3 may influence cognitive performance, and the development of white matter in vivo in a way similar to its known stimulating effect on neurite outgrowth in vitro. These novel observations warrant further replication in independent samples. PMID:17033634
Rujescu, D; Meisenzahl, E M; Krejcova, S; Giegling, I; Zetzsche, T; Reiser, M; Born, C M; Möller, H-J; Veske, A; Gal, A; Finckh, U
The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20-25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a greatly enlarged region of posterior parietal cortex and an expanded motor system and the addition of a ventral premotor area. Higher visual areas in a large temporal lobe facilitated object recognition, and frontal cortex, included granular prefrontal cortex. Auditory cortex included the primary and secondary auditory areas that characterize prosimian and anthropoid primates today. As anthropoids emerged as diurnal primates, the visual system specialized for detailed foveal vision. Other adaptations included an expansion of prefrontal cortex and insular cortex. The human and chimpanzee-bonobo lineages diverged some 6-8 million years ago with brains that were about one-third the size of modern humans. Over the last two million years, the brains of our more recent ancestors increased greatly in size, especially in the prefrontal, posterior parietal, lateral temporal, and insular regions. Specialization of the two cerebral hemispheres for related, but different functions became pronounced, and language and other impressive cognitive abilities emerged. PMID:23529256
Kaas, Jon H
The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20–25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a greatly enlarged region of posterior parietal cortex and an expanded motor system and the addition of a ventral premotor area. Higher visual areas in a large temporal lobe facilitated object recognition, and frontal cortex, included granular prefrontal cortex. Auditory cortex included the primary and secondary auditory areas that characterize prosimian and anthropoid primates today. As anthropoids emerged as diurnal primates, the visual system specialized for detailed foveal vision. Other adaptations included an expansion of prefrontal cortex and insular cortex. The human and chimpanzee-bonobo lineages diverged some 6–8 million years ago with brains that were about one-third the size of modern humans. Over the last two million years, the brains of our more recent ancestors increased greatly in size, especially in the prefrontal, posterior parietal, lateral temporal, and insular regions. Specialization of the two cerebral hemispheres for related, but different functions became pronounced, and language and other impressive cognitive abilities emerged.
Kaas, Jon H.
We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable (3H)cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol\\/mg protein in the cerebral cortex, approximately 42 pmol\\/mg protein in brain microvessels, and approximately 27 pmol\\/mg protein in
Rajesh N. Kalaria; Stephen A. Gravina; James W. Schmidley; George Perry; Sami I. Harik
Quantitative magnetic resonance (MR) imaging allows visualization of age-related changes in the normal human brain from functional, biochemical, and morphologic perspectives. Findings at quantitative MR imaging support age-related microstructural changes in the brain: (a) volume expansion, increased myelination, and axonal growth, which establish neural connectivity in neurodevelopment, followed by (b) volume loss, myelin breakdown, and axonal degradation, leading to the disruption of neural integrity later in life. A rapid growth change followed by a continuous slower change in quantitative MR parameters can be modeled with a logarithmic or exponential decay function. The age dependencies during adulthood often fit a quadratic model for transitional changes with accelerated aging effects or a linear model for steady changes.Understanding these general trends over the human life span can improve assessment for a specific disease by helping determine appropriate study settings. Once a consensus on acquisition techniques and image processing algorithms has been reached, quantitative MR imaging can play an important role in the assessment of disease states affecting the brain. PMID:24025926
Watanabe, Memi; Liao, Joseph H; Jara, Hernán; Sakai, Osamu
The presence of functional cannabinoid CB2 receptors in the CNS has provoked considerable controversy over the past few years. Formerly considered as an exclusively peripheral receptor, it is now accepted that it is also present in limited amounts and distinct locations in the brain of several animal species, including humans. Furthermore, the inducible nature of these receptors under neuroinflammatory conditions, in contrast to CB1, makes them attractive targets for the development of novel therapeutic approaches. In fact, the undesired psychoactive effects caused by CB1 activation have largely limited the clinical use of cannabinoid-related compounds that act on these receptors. In this review some recent findings on the antiinflammatory properties of CB2 receptors are presented, as well as new perspectives that have been obtained based on studies of human postmortem brain samples. In addition, various working hypotheses are also proposed and discussed. PMID:17934510
Benito, C; Tolón, R M; Pazos, M R; Núñez, E; Castillo, A I; Romero, J
The presence of functional cannabinoid CB2 receptors in the CNS has provoked considerable controversy over the past few years. Formerly considered as an exclusively peripheral receptor, it is now accepted that it is also present in limited amounts and distinct locations in the brain of several animal species, including humans. Furthermore, the inducible nature of these receptors under neuroinflammatory conditions, in contrast to CB1, makes them attractive targets for the development of novel therapeutic approaches. In fact, the undesired psychoactive effects caused by CB1 activation have largely limited the clinical use of cannabinoid-related compounds that act on these receptors. In this review some recent findings on the antiinflammatory properties of CB2 receptors are presented, as well as new perspectives that have been obtained based on studies of human postmortem brain samples. In addition, various working hypotheses are also proposed and discussed.
Benito, C; Tolon, R M; Pazos, M R; Nunez, E; Castillo, A I; Romero, J
Contrary to the traditional dogma of being a relatively invariable and quiescent organ lacking the capability to regenerate, there is now widespread evidence that the human brain harbors multipotent neural stem cells, possibly throughout senescence. These cells can divide and give rise to neuroectodermal progeny in vivo and are now regarded as powerful prospective candidates for repairing or enhancing the functional capability of neural tissue in trauma or diseases associated with degeneration or malperfusion. Hopes primarily rest upon techniques to either recruit endogenous stem cells or to utilize exogenous donor-derived material for transplantation. In the search for suitable human cell sources, embryonic, fetal, and adult stem cells appear highly controversial, as they are accompanied by various still-unresolved moral and legal challenges. Fascinatingly, however, recent reports indicate the successful isolation and expansion of viable neural stem cells from the rodent and human brain within a considerable postmortem interval, suggesting that postmortem neural stem cells could potentially become an acceptable alternative cellular resource. This article will provide a brief overview about neural stem cells, their prominent features, and prospects for a cellular therapy, and will furthermore illuminate the cells in particular with respect to their newly discovered postmortem provenience, their advantage as a potential cell source, and several unfolding forensic considerations. Also, important ethical, social, and legal implications arising from this hitherto unpracticed cellular harvest of brain tissue from the deceased are outlined. PMID:16211420
Feldmann, Robert E; Mattern, Rainer
A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the
T. Morimura; K. Kitz; H. Budka
Rationale: Blood platelets have been used ex- tensively as a model system for investigating the role of the serotonin transporter (SERT) in various psychiatric dis- orders, especially depression. However, to date, it is not knownwhetherplateletserotonin(5-HT)transportwouldbe related to that in brain. Objectives: We examined 5-HT transport kinetics simultaneously in human blood platelets andhumancorticalbrainsynaptosomestodeterminewhether they were correlated. Methods: Blood platelets and synap-
Jeffrey L. Rausch; Maria E. Johnson; Junqing Li; Julian Hutcheson; Benjamin M. Carr; Katina M. Corley; Amanda B. Gowans; Joseph Smith
Among mediators of oxidative stress, highly reactive secondary aldehydic lipid peroxidation products can initiate the processes\\u000a of spontaneous mutagenesis and carcinogenesis and can also act as a growth-regulating factors and signaling molecules. We\\u000a explored whether these aldehydes and histone H3 mRNA levels could serve as biomarkers of malignancy and predictive factor\\u000a in human brain astrocytomas. Histone H3 mRNA, a biomarker
Alicja Zajdel; Adam Wilczok; Jerzy Slowinski; Joanna Orchel; Urszula Mazurek
BACKGROUND & AIMS: Lipid islands are a common finding in the gastric mucosa, but their pathogenesis has not yet been established. The aim of this study was to investigate the morphology and immunophenotype of the various cells in lipid islands and to consider the possible mechanisms involved in the pathogenesis of these lesions. METHODS: Morphological and immunohistochemical investigations using antibodies
E Kaiserling; H Heinle; H Itabe; T Takano; W Remmele
A critical component of decision making is the ability to adjust criteria for classifying stimuli. fMRI and drift diffusion models were used to explore the neural representations of perceptual criteria in decision making. The specific focus was on the relative engagement of perceptual- and decision-related neural systems in response to adjustments in perceptual criteria. Human participants classified visual stimuli as big or small based on criteria of different sizes, which effectively biased their choices toward one response over the other. A drift diffusion model was fit to the behavioral data to extract estimates of stimulus size, criterion size, and difficulty for each participant and condition. These parameter values were used as modulated regressors to create a highly constrained model for the fMRI analysis that accounted for several components of the decision process. The results show that perceptual criteria values were reflected by activity in left inferior temporal cortex, a region known to represent objects and their physical properties, whereas stimulus size was reflected by activation in occipital cortex. A frontoparietal network of regions, including dorsolateral prefrontal cortex and superior parietal lobule, corresponded to the decision variables resulting from the downstream stimulus-criterion comparison, independent of stimulus type. The results provide novel evidence that perceptual criteria are represented in stimulus space and serve as inputs to be compared with the presented stimulus, recruiting a common network of decision regions shown to be active in other simple decisions. This work advances our understanding of the neural correlates of decision flexibility and adjustments of behavioral bias. PMID:23175825
White, Corey N; Mumford, Jeanette A; Poldrack, Russell A
We have used a crossreactive monoclonal antibody against a mouse neural cell adhesion molecule (N-CAM) to characterize and purify an antigen from embryonic and neonatal human brain. This antigen was identified as human N-CAM according to several criteria, including molecular weight, sialic acid content, amino acid composition, analysis of peptide fragments, reactivity with a variety of anti-CAM antibodies, and activity of the antigen in assays of cell and membrane vesicle aggregation. The findings make feasible an exploration of the possible role of N-CAM in various neurological disorders. Images
McClain, D A; Edelman, G M
Noninvasive studies of human brain function hold great potential to unlock mysteries of the human mind. The complexity of data generated by such studies, however, has prompted various simplifying assumptions during analysis. Although this has enabled considerable progress, our current understanding is partly contingent upon these assumptions. An emerging approach embraces the complexity, accounting for the fact that neural representations are widely distributed, neural processes involve interactions between regions, interactions vary by cognitive state, and the space of interactions is massive. Because what you see depends on how you look, such unbiased approaches provide the greatest flexibility for discovery.
Turk-Browne, Nicholas B.
Studies of patients with focal brain lesions remain critical components of research programs attempting to understand human brain function. Whereas functional imaging typically reveals activity in distributed brain regions that are involved in a task, lesion studies can define which of these brain regions are necessary for a cognitive process. Further, lesion studies are less critical regarding the selection of
N. G. Müller; R. T. Knight
One human brain was used for this study. The brain was fixed in 5% formalin for two months, rinced and cut in two halves on the sagital plane. Both brain halves were sagitally sliced at a tickness of 4 mm. From each brain half we selected 8 slices and plastinated them with P40 using different immersion and impregnation conditions. Two
Mircea-Constantin Sora; Peter Brugger; Hannes Traxler
As neuroscience learns more about the causes of human behaviors, it will give us new ways to change those behaviors. When behaviors are caused by "brain diseases," effective actions that intervene directly in the brain will be readily accepted, but what about direct brain interventions that treat brain-based causes of socially disfavored behaviors that are not generally viewed as diseases? PMID:22261682
Greely, H T
Background Measuring allelic RNA expression ratios is a powerful approach for detecting cis-acting regulatory variants, RNA editing, loss of heterozygosity in cancer, copy number variation, and allele-specific epigenetic gene silencing. Whole transcriptome RNA sequencing (RNA-Seq) has emerged as a genome-wide tool for identifying allelic expression imbalance (AEI), but numerous factors bias allelic RNA ratio measurements. Here, we compare RNA-Seq allelic ratios measured in nine different human brain regions with a highly sensitive and accurate SNaPshot measure of allelic RNA ratios, identifying factors affecting reliable allelic ratio measurement. Accounting for these factors, we subsequently surveyed the variability of RNA editing across brain regions and across individuals. Results We find that RNA-Seq allelic ratios from standard alignment methods correlate poorly with SNaPshot, but applying alternative alignment strategies and correcting for observed biases significantly improves correlations. Deploying these methods on a transcriptome-wide basis in nine brain regions from a single individual, we identified genes with AEI across all regions (SLC1A3, NHP2L1) and many others with region-specific AEI. In dorsolateral prefrontal cortex (DLPFC) tissues from 14 individuals, we found evidence for frequent regulatory variants affecting RNA expression in tens to hundreds of genes, depending on stringency for assigning AEI. Further, we find that the extent and variability of RNA editing is similar across brain regions and across individuals. Conclusions These results identify critical factors affecting allelic ratios measured by RNA-Seq and provide a foundation for using this technology to screen allelic RNA expression on a transcriptome-wide basis. Using this technology as a screening tool reveals tens to hundreds of genes harboring frequent functional variants affecting RNA expression in the human brain. With respect to RNA editing, the similarities within and between individuals leads us to conclude that this post-transcriptional process is under heavy regulatory influence to maintain an optimal degree of editing for normal biological function.
Objective Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing. Methods We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15–22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB’s integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed. Results Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes. Interpretation Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.
Abolmaali, Nasreddin; Krone, Franziska; Hoffmann, Andre; Holfeld, Elisabeth; Vorwerk, Peter; Kramm, Christof; Gruhn, Bernd; Koustenis, Elisabeth; Hernaiz-Driever, Pablo; Mandal, Rakesh; Suttorp, Meinolf; Hummel, Thomas; Ikonomidou, Chrysanthy; Kirschbaum, Clemens; Smolka, Michael N.
We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations
Paul M. Thompson; Kiralee M. Hayashi; Sara L. Simon; Jennifer A. Geaga; Michael S. Hong; Yihong Sui; Jessica Y. Lee; Arthur W. Toga; Walter Ling; Edythe D. London
Brain tissue biopsies are required to histologically diagnose brain tumors, but current approaches are limited by tissue characterization at the time of surgery. Emerging technologies such as mass spectrometry imaging can enable a rapid direct analysis of cancerous tissue based on molecular composition. Here, we illustrate how gliomas can be rapidly classified by desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine learning. DESI-MS imaging was carried out on 36 human glioma samples, including oligodendroglioma, astrocytoma, and oligoastrocytoma, all of different histologic grades and varied tumor cell concentration. Gray and white matter from glial tumors were readily discriminated and detailed diagnostic information could be provided. Classifiers for subtype, grade, and concentration features generated with lipidomic data showed high recognition capability with more than 97% cross-validation. Specimen classification in an independent validation set agreed with expert histopathology diagnosis for 79% of tested features. Together, our findings offer proof of concept that intraoperative examination and classification of brain tissue by mass spectrometry can provide surgeons, pathologists, and oncologists with critical and previously unavailable information to rapidly guide surgical resections that can improve management of patients with malignant brain tumors. PMID:22139378
Eberlin, Livia S; Norton, Isaiah; Dill, Allison L; Golby, Alexandra J; Ligon, Keith L; Santagata, Sandro; Cooks, R Graham; Agar, Nathalie Y R
Brain tissue biopsies are required to histologically diagnose brain tumors, but current approaches are limited by tissue characterization at the time of surgery. Emerging technologies such as mass spectrometry imaging can enable a rapid direct analysis of cancerous tissue based on molecular composition. Here we illustrate how gliomas can be rapidly classified by desorption electrospray mass spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine learning. DESI-MS imaging was performed on thirty-six human glioma samples, including oligodendroglioma, astrocytoma and oligoastrocytoma, all of different histologic grades and varied tumor cell concentration. Grey and white matter from glial tumors were readily discriminated and detailed diagnostic information could be provided. Classifiers for subtype, grade and concentration features generated with lipidomic data showed high recognition capability with >97% cross-validation. Specimen classification in an independent validation set agreed with expert histopathology diagnosis for 81% of tested features. Together, our findings offer proof of concept that intra-operative examination and classification of brain tissue by mass spectrometry can provide surgeons, pathologists, and oncologists with critical and previously unavailable information to rapidly guide surgical resections that can improve management of patients with malignant brain tumors.
Eberlin, Livia S.; Norton, Isaiah; Dill, Allison L.; Golby, Alexandra J.; Ligon, Keith L.; Santagata, Sandro; Cooks, R. Graham; Agar, Nathalie Y.R.
We present in vivo images of the human brain acquired with an ultralow field MRI (ULFMRI) system operating at a magnetic field B0 ? 130 ?T. The system features prepolarization of the proton spins at Bp ? 80 mT and detection of the NMR signals with a superconducting, second-derivative gradiometer inductively coupled to a superconducting quantum interference device (SQUID). We report measurements of the longitudinal relaxation time T1 of brain tissue, blood, and scalp fat at B0 and Bp, and cerebrospinal fluid at B0. We use these T1 values to construct inversion recovery sequences that we combine with Carr–Purcell–Meiboom–Gill echo trains to obtain images in which one species can be nulled and another species emphasized. In particular, we show an image in which only blood is visible. Such techniques greatly enhance the already high intrinsic T1 contrast obtainable at ULF. We further present 2D images of T1 and the transverse relaxation time T2 of the brain and show that, as expected at ULF, they exhibit similar contrast. Applications of brain ULFMRI include integration with systems for magnetoencephalography. More generally, these techniques may be applicable, for example, to the imaging of tumors without the need for a contrast agent and to modalities recently demonstrated with T1? contrast imaging (T1 in the rotating frame) at fields of 1.5 T and above.
Inglis, Ben; Buckenmaier, Kai; SanGiorgio, Paul; Pedersen, Anders F.; Nichols, Matthew A.; Clarke, John
The expression of the EGF receptor, c-erbB-2 and PDGF receptor proteins has been studied in a series of human brain tumour biopsies and cell lines. Western blotting was used to determine the amount of protein present and their intrinsic and ligand promoted enzyme activities were studied by immunoprecipitation followed by autophosphorylation. EGF receptors were found to be expressed at very high levels in 40% of primary tumour biopsies, but at uniformly low levels in tumour derived cell lines. The c-erbB-2 protein was not detected in tumour biopsies, but was present at variable, but low levels in extracts of tumour cell lines. PDGF receptors were also found at moderate to low levels in both primary tumours and cell lines. The EGF receptor gene was amplified in four out of 14 primary tumours and this generally correlated with high levels of protein expression. The c-erbB-2 gene was not amplified. Employing the polymerase chain reaction and sequence specific oligonucleotides as probes there was no evidence of mutations in the c-erbB-2 gene transmembrane region. These results suggest that alterations of expression of the EGF receptor may play a role in human brain tumours. There was however no evidence for aberrant expression of the c-erbB-2 protein. Additional experiments are required to assess the influence of PDGF receptor expression in brain tumour cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6
Tuzi, N. L.; Venter, D. J.; Kumar, S.; Staddon, S. L.; Lemoine, N. R.; Gullick, W. J.
Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a "rich club"-a high-cost, high-capacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical-subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants. PMID:24799693
Ball, Gareth; Aljabar, Paul; Zebari, Sally; Tusor, Nora; Arichi, Tomoki; Merchant, Nazakat; Robinson, Emma C; Ogundipe, Enitan; Rueckert, Daniel; Edwards, A David; Counsell, Serena J
Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a “rich club”—a high-cost, high-capacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical–subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants.
Ball, Gareth; Aljabar, Paul; Zebari, Sally; Tusor, Nora; Arichi, Tomoki; Merchant, Nazakat; Robinson, Emma C.; Ogundipe, Enitan; Rueckert, Daniel; Edwards, A. David; Counsell, Serena J.
Why Neuroergonomics. To design effective human-machine systems, we must (1) Understand mind in relation to work and technology -- ergonomics (2) Mind cannot be understood without studying the brain -- neuroscience (3) Hence study brain and mind in complex...
Rapid progress in effective methods to image brain functions has revolutionized neuroscience. It is now possible to study noninvasively in humans neural processes that were previously only accessible in experimental animals and in brain-injured patients. In this endeavor, positron emission tomography has been the leader, but the superconducting quantum interference device-based magnetoencephalography (MEG) is gaining a firm role, too. With the advent of instruments covering the whole scalp, MEG, typically with 5-mm spatial and 1-ms temporal resolution, allows neuroscientists to track cortical functions accurately in time and space. We present five representative examples of recent MEG studies in our laboratory that demonstrate the usefulness of whole-head magnetoencephalography in investigations of spatiotemporal dynamics of cortical signal processing. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7
Lounasmaa, O V; Hamalainen, M; Hari, R; Salmelin, R
Quantitative magnetization transfer (qMT) imaging yields indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular to free pool size ratio (PSR), which has been shown to be correlated with myelin content in white matter. Because of the long scan times required for whole-brain imaging (?20-30 min), qMT studies of the human brain have not found widespread application. Herein, we investigated whether the increased signal-to-noise ratio available at 7.0 T could be used to reduce qMT scan times. More specifically, we developed a selective inversion recovery (SIR) qMT imaging protocol with a i) novel transmit radiofrequency (B(1)(+)) and static field (B(0)) insensitive inversion pulse, ii) turbo field-echo readout, and iii) reduced TR. In vivo qMT data were obtained in the brains of healthy volunteers at 7.0 T using the resulting protocol (scan time?40 s/slice, resolution=2 × 2 × 3 mm(3)). Reliability was also assessed in repeated acquisitions. The results of this study demonstrate that SIR qMT imaging can be reliably performed within the radiofrequency power restrictions present at 7.0 T, even in the presence of large B(1)(+) and B(0) inhomogeneities. Consistent with qMT studies at lower field strengths, the observed PSR values were higher in white matter (mean±SD=17.6 ± 1.3%) relative to gray matter (10.3 ± 1.6%) at 7.0 T. In addition, regional variations in PSR were observed in white matter. Together, these results suggest that qMT measurements are feasible at 7.0 T and may eventually allow for the high-resolution assessment of changes in composition throughout the normal and diseased human brain in vivo. PMID:22940589
Dortch, Richard D; Moore, Jay; Li, Ke; Jankiewicz, Marcin; Gochberg, Daniel F; Hirtle, Jane A; Gore, John C; Smith, Seth A
Eight elements (i.e. K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) were measured in 50 different regions of 12 normal human brains by particle-induced X-ray emission (PIXE) analysis. The dry weight concentrations of K, Fe, Cu, Zn, Se, and Rb were consistently higher for gray than for white matter areas. The K, Zn and Se concentrations for the regions of mixed composition and, to some extent, also the Rb concentrations, were intermediate between the gray and white matter values, and they tended to decrease with decreasing neuron density. The mean dry weight concentrations of K, Ca, Zn, Se, and Rb in the various brain regions were highly correlated with the mean wet-to-dry weight ratios of these regions. For Mn, Fe, and Cu, however, such a correlation was not observed, and these elements exhibited elevated levels in several structures of the basal ganglia. For K, Fe, and Se the concentrations seemed to change with age. A hierarchical cluster analysis indicated that the structures clustered into two large groups, one comprising gray and mixed matter regions, the other white and mixed matter areas. Brain structures involved in the same physiological function or morphologically similar regions often conglomerated in a single subcluster. PMID:2594142
Duflou, H; Maenhaut, W; De Reuck, J
Analysis of changes in intracellular signal transduction will provide clear images of the projected target neurons. We have recently developed a technique which allows second-messenger imaging of changes in intracellular signal transduction which is activated in parallel with phosphoinositide (PI) turnover. Using carbon-11-labeled 1,2-diacylglycerol (DAG), we have recently succeeded in making an image of intracellular signal transduction during the course of synaptic transmission in human brains. When five healthy volunteers were examined by this technique, they had high activity in the associate field, in particular the prefrontal area. In the absence of paradigm loading, the associate field was unilaterally active, and human subjects showed predominant activity in the right prefrontal area. Activation of the ipsilateral supraorbital region and the superior temporal area was also seen at the same time. In conclusion, no previous study has directly demonstrated the unilateral predominance of the activity in the associate fields (projected target area) and the accompanying areas. Unlike the conventional positron-labeled compounds which did not permit visualization of activation of the associate fields, our technique can measure the PI turnover, as a postsynaptic response, and thus provide clear images of the projected target nerve cells in relation to higher cortical function in human brain.
Imahori, Y.; Fujii, R.; Ueda, S. [Kyoto Prefectural Univ. of Medicine (Japan)] [and others
We investigated large-scale systems organization of the whole human brain using functional magnetic resonance imaging (fMRI) data acquired from healthy volunteers in a no-task or 'resting' state. Images were parcellated using a prior anatomical template, yielding regional mean time series for each of 90 regions (major cortical gyri and subcortical nuclei) in each subject. Significant pairwise functional connections, defined by the group mean inter-regional partial correlation matrix, were mostly either local and intrahemispheric or symmetrically interhemispheric. Low-frequency components in the time series subtended stronger inter-regional correlations than high-frequency components. Intrahemispheric connectivity was generally related to anatomical distance by an inverse square law; many symmetrical interhemispheric connections were stronger than predicted by the anatomical distance between bilaterally homologous regions. Strong interhemispheric connectivity was notably absent in data acquired from a single patient, minimally conscious following a brainstem lesion. Multivariate analysis by hierarchical clustering and multidimensional scaling consistently defined six major systems in healthy volunteers-- corresponding approximately to four neocortical lobes, medial temporal lobe and subcortical nuclei- - that could be further decomposed into anatomically and functionally plausible subsystems, e.g. dorsal and ventral divisions of occipital cortex. An undirected graph derived by thresholding the healthy group mean partial correlation matrix demonstrated local clustering or cliquishness of connectivity and short mean path length compatible with prior data on small world characteristics of non-human cortical anatomy. Functional MRI demonstrates a neurophysiological architecture of the normal human brain that is anatomically sensible, strongly symmetrical, disrupted by acute brain injury, subtended predominantly by low frequencies and consistent with a small world network topology. PMID:15635061
Salvador, Raymond; Suckling, John; Coleman, Martin R; Pickard, John D; Menon, David; Bullmore, Ed
A cDNA library from human basal ganglia was screened with oligonucleotide probes corresponding to portions of the amino acid sequence of human serum cholinesterase. Five overlapping clones, representing 2.4 kilobases, were isolated. The sequenced cDNA contained 207 base pairs of coding sequence 5' to the amino terminus of the mature protein in which there were four ATG translation start sites in the same reading frame as the protein. Only the ATG coding for Met-(-28) lay within a favorable consensus sequence for functional initiators. There were 1722 base pairs of coding sequence corresponding to the protein found circulating in human serum. The amino acid sequence deduced from the cDNA exactly matched the 574 amino acid sequence of human serum cholinesterase, as previously determined by Edman degradation. Therefore, our clones represented cholinesterase rather than acetylcholinesterase. It was concluded that the amino acid sequences of cholinesterase from two different tissues, human brain and human serum, were identical. Hybridization of genomic DNA blots suggested that a single gene, or very few genes coded for cholinesterase.
McTiernan, C.; Adkins, S.; Chatonnet, A.; Vaughan, T.A.; Bartels, C.F.; Kott, M.; Rosenberry, T.L.; La Du, B.N.; Lockridge, O.
The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients. PMID:23719806
Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M
Looking at ambiguous figures results in rivalry with spontaneous alternation between two percepts. Using event-related functional magnetic resonance imaging, we localized transient human brain activity changes during perceptual reversals. Activation occurred in ventral occipital and intraparietal higher-order visual areas, deactivation in primary visual cortex and the pulvinar. Thus, without any physical stimulus changes, salient perceptual flips briefly engage widely separated specialized cortical areas, but are also associated with intermittent activity breakdown in structures putatively maintaining perceptual stability. Together, the dynamics of integrative perceptual experience are reflected in rapid spatially differentiated activity modulation within a cooperative set of neural structures.
Kleinschmidt, A; Buchel, C; Zeki, S; Frackowiak, R S
Prenatal neuroimaging requires reference models that reflect the normal spectrum of fetal brain development, and summarize observations from a representative sample of individuals. Collecting a sufficiently large data set of manually annotated data to construct a comprehensive in vivo atlas of rapidly developing structures is challenging but necessary for large population studies and clinical application. We propose a method for the semi-supervised learning of a spatio-temporal latent atlas of fetal brain development, and corresponding segmentations of emerging cerebral structures, such as the ventricles or cortex. The atlas is based on the annotation of a few examples, and a large number of imaging data without annotation. It models the morphological and developmental variability across the population. Furthermore, it serves as basis for the estimation of a structures' morphological age, and its deviation from the nominal gestational age during the assessment of pathologies. Experimental results covering the gestational period of 20-30 gestational weeks demonstrate segmentation accuracy achievable with minimal annotation, and precision of morphological age estimation. Age estimation results on fetuses suffering from lissencephaly demonstrate that they detect significant differences in the age offset compared to a control group. PMID:24080527
Dittrich, Eva; Riklin Raviv, Tammy; Kasprian, Gregor; Donner, René; Brugger, Peter C; Prayer, Daniela; Langs, Georg
Blood smears from 13 patients infected with Babesia microti were reviewed to define the range of morphologic characteristics of the organism. Organisms resembling rings of Plasmodium falciparum were the predominant forms in all patients' blood smears. Babesia microti and Plasmodium spp. may be differentiated by the presence of pigment deposits in erythrocytes parasitized with mature stages of Plasmodium. PMID:7188717
Healy, G R; Ruebush, T K
A system for culturing human fetal liver cells in monolayers is described and the effects of various conditions of growth on the morphology and function of the cultured cells are presented. The addition of 10% calf serum or 1% human serum to the growth medium accelerated the proliferation of the liver cells, with subsequent loss of characteristic morphology and specific functional activity. In the absence of serum, the cultured liver cells retained their morphology and their function for at least 4 wk, as evidenced by secretion of serum albumin and storage of glycogen and iron. PMID:4104969
Bissell, D M; Tilles, J G
A system for culturing human fetal liver cells in monolayers is described and the effects of various conditions of growth on the morphology and function of the cultured cells are presented. The addition of 10% calf serum or 1% human serum to the growth medium accelerated the proliferation of the liver cells, with subsequent loss of characteristic morphology and specific functional activity. In the absence of serum, the cultured liver cells retained their morphology and their function for at least 4 wk, as evidenced by secretion of serum albumin and storage of glycogen and iron.
Bissell, D. Montgomery; Tilles, Jeremiah G.
The brain is not a passive sensory-motor analyzer driven by environmental stimuli, but actively maintains ongoing representations that may be involved in the coding of expected sensory stimuli, prospective motor responses, and prior experience. Spontaneous cortical activity has been proposed to play an important part in maintaining these ongoing, internal representations, although its functional role is not well understood. One spontaneous signal being intensely investigated in the human brain is the interregional temporal correlation of the blood-oxygen level-dependent (BOLD) signal recorded at rest by functional MRI (functional connectivity-by-MRI, fcMRI, or BOLD connectivity). This signal is intrinsic and coherent within a number of distributed networks whose topography closely resembles that of functional networks recruited during tasks. While it is apparent that fcMRI networks reflect anatomical connectivity, it is less clear whether they have any dynamic functional importance. Here, we demonstrate that visual perceptual learning, an example of adult neural plasticity, modifies the resting covariance structure of spontaneous activity between networks engaged by the task. Specifically, after intense training on a shape-identification task constrained to one visual quadrant, resting BOLD functional connectivity and directed mutual interaction between trained visual cortex and frontal-parietal areas involved in the control of spatial attention were significantly modified. Critically, these changes correlated with the degree of perceptual learning. We conclude that functional connectivity serves a dynamic role in brain function, supporting the consolidation of previous experience.
Lewis, Christopher M.; Baldassarre, Antonello; Committeri, Giorgia; Romani, Gian Luca; Corbetta, Maurizio
To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilites for the delta, theta, alpha and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans.
van Beijsterveldt, C. E.; Molenaar, P. C.; de Geus, E. J.; Boomsma, D. I.
Abstract DJ-1, the product of a causative gene of a familial form of Parkinson disease, undergoes preferential oxidation of Cys106 (cysteine residue at position 106) under oxidative stress. Using specific monoclonal antibodies against Cys106 oxidized DJ-1 (oxDJ-1), we examined oxDJ-1 immunoreactivity in brain sections from DJ-1 knockout and wild-type mice and in human brain sections from cases classified into different Lewy body stages of Parkinson disease and Parkinson disease with dementia. Oxidized DJ-1 immunoreactivity was prominently observed in neuromelanin-containing neurons and neuron processes of the substantia nigra; Lewy bodies also showed oxDJ-1 immunoreactivity. Oxidized DJ-1 was also detected in astrocytes in the striatum, in neurons and glia in the red nucleus, and in the inferior olivary nucleus, all of which are related to regulation of movement. These observations suggest the relevance of DJ-1 oxidation to homeostasis in multiple brain regions, including neuromelanin-containing neurons of the substantia nigra, and raise the possibility that oxDJ-1 levels might change during the progression of Lewy body–associated neurodegenerative diseases.
Saito, Yoshiro; Miyasaka, Tomohiro; Hatsuta, Hiroyuki; Takahashi-Niki, Kazuko; Hayashi, Kojiro; Mita, Yuichiro; Kusano-Arai, Osamu; Iwanari, Hiroko; Ariga, Hiroyoshi; Hamakubo, Takao; Yoshida, Yasukazu; Niki, Etsuo; Murayama, Shigeo; Ihara, Yasuo; Noguchi, Noriko
DJ-1, the product of a causative gene of a familial form of Parkinson disease, undergoes preferential oxidation of Cys106 (cysteine residue at position 106) under oxidative stress. Using specific monoclonal antibodies against Cys106 oxidized DJ-1 (oxDJ-1), we examined oxDJ-1 immunoreactivity in brain sections from DJ-1 knockout and wild-type mice and in human brain sections from cases classified into different Lewy body stages of Parkinson disease and Parkinson disease with dementia. Oxidized DJ-1 immunoreactivity was prominently observed in neuromelanin-containing neurons and neuron processes of the substantia nigra; Lewy bodies also showed oxDJ-1 immunoreactivity. Oxidized DJ-1 was also detected in astrocytes in the striatum, in neurons and glia in the red nucleus, and in the inferior olivary nucleus, all of which are related to regulation of movement. These observations suggest the relevance of DJ-1 oxidation to homeostasis in multiple brain regions, including neuromelanin-containing neurons of the substantia nigra, and raise the possibility that oxDJ-1 levels might change during the progression of Lewy body-associated neurodegenerative diseases. PMID:24918637
Saito, Yoshiro; Miyasaka, Tomohiro; Hatsuta, Hiroyuki; Takahashi-Niki, Kazuko; Hayashi, Kojiro; Mita, Yuichiro; Kusano-Arai, Osamu; Iwanari, Hiroko; Ariga, Hiroyoshi; Hamakubo, Takao; Yoshida, Yasukazu; Niki, Etsuo; Murayama, Shigeo; Ihara, Yasuo; Noguchi, Noriko
Creativity is a vast construct, seemingly intractable to scientific inquiry—perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR). Behaviorally, one can limit the “blind variation” component to idea generation tests as manifested by measures of divergent thinking. The “selective retention” component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS). We also review lesion studies, considered to be the “gold standard” of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981). We provide a perspective, involving aspects of the default mode network (DMN), which might provide a “first approximation” regarding how creative cognition might map on to the human brain.
Jung, Rex E.; Mead, Brittany S.; Carrasco, Jessica; Flores, Ranee A.
Brain maturation is a complex process that continues well beyond infancy, and adolescence is thought to be a key period of brain rewiring. To assess structural brain maturation from childhood to adulthood, we charted brain development in subjects aged 5 to 30 years using diffusion tensor magnetic resonance imaging, a novel brain imaging technique that is sensitive to axonal packing and
C. Lebel; L. Walker; A. Leemans; L. Phillips; C. Beaulieu
Context: Although maternal hypothyroxinemia is suggested to be related to various adverse consequences in a child's neurodevelopment, the underlying neurobiology is largely unknown. Objective: The objective of the study was to examine the relationship between maternal hypothyroxinemia in early pregnancy and children's nonverbal intelligence quotient (IQ). Furthermore, we explored whether global brain volumes, cortical thickness, and brain surface area differed between children exposed prenatally to hypothyroxinemia and healthy controls. Design and Setting: The study included a large population-based prospective birth cohort in The Netherlands. Participants: A total of 3727 mother-child pairs with data on prenatal thyroid function at less than 18 weeks of gestation and nonverbal IQ at 6 years participated in the study. In 652 children, brain imaging was performed at 8 years of age. Main Measures: Maternal hypothyroxinemia was defined as free T4 in the lowest 5% of the sample, whereas TSH was in the normal range. At 6 years, children's IQ was assessed using a Dutch test battery. Global brain volumetric measures, cortical thickness, and surface area were assessed using high-resolution structural magnetic resonance imaging. Results: The children of mothers with hypothyroxinemia in early pregnancy scored 4.3 points IQ lower than the children of mothers with normal thyroid status (95% confidence interval -6.68, -1.81; P = .001). After adjustment for multiple testing, we did not find any differences in brain volumetric measures, cortical thickness, and surface area between children exposed prenatally to hypothyroxinemia and controls. Conclusions: Our findings confirm a large adverse effect of maternal hypothyroxinemia on children's nonverbal IQ at school age. However, we found no evidence that maternal hypothyroxinemia is associated with differences in brain morphology in school-age children. PMID:24684462
Ghassabian, Akhgar; El Marroun, Hanan; Peeters, Robin P; Jaddoe, Vincent W; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning; White, Tonya
Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity. PMID:17278586
Linninger, Andreas A; Xenos, Michalis; Zhu, David C; Somayaji, MahadevaBharath R; Kondapalli, Srinivasa; Penn, Richard D
Background Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT) and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF) 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP) complex. Objective To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. Materials and Methods Eight Low Grade Astrocytomas (LGA), 11 Anaplastic Astrocytomas (AA) and 11 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP) assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. Results LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. Conclusions In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.
La Torre, Domenico; Conti, Alfredo; Aguennouz, M?Hammed; De Pasquale, Maria Grazia; Romeo, Sara; Angileri, Filippo Flavio; Cardali, Salvatore; Tomasello, Chiara; Alafaci, Concetta; Germano, Antonino
For over a century, models of pitch perception have been based on the frequency composition of the sound. Pitch phenomena can also be explained, however, in terms of the time structure, or temporal regularity, of sounds. To locate the mechanism for the detection of temporal regularity in humans, we used functional imaging and a 'delay-and-add' noise, which activates all frequency regions uniformly, like noise, but which nevertheless produces strong pitch perceptions and tuneful melodies. This stimulus has temporal regularity that can be systematically altered. We found that the activity of primary auditory cortex increased with the regularity of the sound. Moreover, a melody composed of delay-and-add 'notes' produced a distinct pattern of activation in two areas of the temporal lobe distinct from primary auditory cortex. These results suggest a hierarchical analysis of time structure in the human brain. PMID:10196534
Griffiths, T D; Büchel, C; Frackowiak, R S; Patterson, R D
Modeling and simulation based on mechanisms is important in order to design and control mechatronic systems. In particular, in-depth understanding and realistic modeling of biological systems is indispensable for biomechatronics. This paper presents open brain simulator, which estimates the neural state of human through external measurement for the purpose of improving motor and social skills. Macroscopic anatomical nervous systems model was built which can be connected to the musculoskeletal model. Microscopic anatomical and physiological neural models were interfaced to the macroscopic model. Neural activities of somatosensory area and Purkinje cell were calculated from motion capture data. The simulator provides technical infrastructure for human biomechatronics, which is promising for the novel diagnosis of neurological disorders and their treatments through medication and movement therapy, and for motor learning support system supporting acquisition of motor skill considering neural mechanism.
Otake, Mihoko; Takagi, Toshihisa; Asama, Hajime
We hypothesized that myelin breakdown in vulnerable late-myelinating regions releases oligodendrocyte- and myelin-associated iron that promotes amyloid beta (A?) oligomerization, its associated toxicity, and the deposition of oligomerized A? and iron in neuritic plaques observed in Alzheimer’s disease (AD). The model was tested by using published maps of cortical myelination from 1901 and recent in vivo imaging maps of A? deposits in humans. The data show that in AD, radiolabeled ligands detect A? deposition in a distribution that matches the map of late-myelinating regions. Furthermore, the strikingly lower ability of this imaging ligand to bind A? in animal models is consistent with the much lower levels of myelin and associated iron levels in rodents when compared with humans. The hypotheses derived from the “myelin model” are testable with current imaging methods and have important implications for therapeutic interventions that should be expanded to include novel targets such as oligodendrocytes, myelin, and brain iron.
Bartzokis, George; Lu, Po H.; Mintz, Jim
What constitutes normal cortical dynamics in healthy human subjects is a major question in systems neuroscience. Numerous in vitro and in vivo animal studies have shown that ongoing or resting cortical dynamics are characterized by cascades of activity across many spatial scales, termed neuronal avalanches. In experiment and theory, avalanche dynamics are identified by two measures: (1) a power law in the size distribution of activity cascades with an exponent of ?3/2 and (2) a branching parameter of the critical value of 1, reflecting balanced propagation of activity at the border of premature termination and potential blowup. Here we analyzed resting-state brain activity recorded using noninvasive magnetoencephalography (MEG) from 124 healthy human subjects and two different MEG facilities using different sensor technologies. We identified large deflections at single MEG sensors and combined them into spatiotemporal cascades on the sensor array using multiple timescales. Cascade size distributions obeyed power laws. For the timescale at which the branching parameter was close to 1, the power law exponent was ?3/2. This relationship was robust to scaling and coarse graining of the sensor array. It was absent in phase-shuffled controls with the same power spectrum or empty scanner data. Our results demonstrate that normal cortical activity in healthy human subjects at rest organizes as neuronal avalanches and is well described by a critical branching process. Theory and experiment have shown that such critical, scale-free dynamics optimize information processing. Therefore, our findings imply that the human brain attains an optimal dynamical regime for information processing.
Shriki, Oren; Alstott, Jeff; Carver, Frederick; Holroyd, Tom; Henson, Richard N.A.; Smith, Marie L.; Coppola, Richard; Bullmore, Edward; Plenz, Dietmar
Background The multifunctional glycoprotein clusterin has been associated with late-onset Alzheimer’s disease (AD). Further investigation to define the role of clusterin in AD phenotypes would be aided by the development of techniques to quantify level, potential post-translational modifications, and isoforms of clusterin. We have developed a quantitative technique based on multiple reaction monitoring (MRM) mass spectrometry to measure clusterin in human postmortem brain tissues. Results A stable isotope-labeled concatenated peptide (QconCAT) bearing selected peptides from clusterin was expressed with an in vitro translation system and purified. This clusterin QconCAT was validated for use as an internal standard for clusterin quantification using MRM mass spectrometry. Measurements were performed on the human postmortem frontal and temporal cortex from control and severe AD cases. During brain tissues processing, 1% SDS was used in the homogenization buffer to preserve potential post-translational modifications of clusterin. However, MRM quantifications in the brain did not suggest phosphorylation of Thr393, Ser394, and Ser396 residues reported for clusterin in serum. MRM quantifications in the frontal cortex demonstrated significantly higher (P?0.01) level of clusterin in severe AD group (39.1?±?9.1 pmol/mg tissue protein) in comparison to control group (25.4?±?4.4 pmol/mg tissue protein). In the temporal cortex, the clusterin levels were not significantly different, 29.0?±?7.9 pmol/mg tissue protein and 28.0?±?8.4 pmol/mg tissue protein in control and severe AD groups, respectively. Conclusions The proposed protocol is a universal quantitative technique to assess expression level of clusterin. It is expected that application of this protocol to quantification of various clusterin isoforms and potential post-translational modifications will be helpful in addressing the role of clusterin in AD.
We used the technique of functional magnetic resonance imaging to chart the colour pathways in the human brain beyond V4. We asked subjects to view objects that were dressed in natural and unnatural colours as well as their achromatic counterparts and compared the activity produced in the brain by each condition. The results showed that both naturally and unnaturally coloured objects activate a pathway extending from V1 to V4, though not overlapping totally the activity produced by viewing abstract coloured Mondrian scenes. Normally coloured objects activated, in addition, more anterior parts of the fusiform gyrus, the hippocampus and the ventrolateral frontal cortex. Abnormally coloured objects, by contrast, activated the dorsolateral frontal cortex. A study of the cortical covariation produced by these activations revealed that activity in large parts of the occipital lobe covaried with each. These results, considered against the background of previous physiological and clinical studies, allow us to discern three broad cortical stages of colour processing in the human brain. The first is based on V1 and possibly V2 and is concerned mainly with registering the presence and intensity of different wavelengths, and with wavelength differencing. The second stage is based on V4 and is concerned with automatic colour constancy operations, without regard to memory, judgement and learning. The third stage, based on the inferior temporal and frontal cortex, is more concerned with object colours. The results we report, as well as the schema that we suggest, also allow us to reconcile the computational theory of Land, implemented without regard to cognitive factors such as memory and learning, and the cognitive systems of Helmholtz and Hering, which view such factors as critical in the determination of colours. PMID:9762956
Zeki, S; Marini, L
Creatine kinase activity and high-energy phosphate concentration have been investigated using localized 31P spectroscopy in the human brain in vivo. The phase-modulated rotating frame imaging technique, incorporating magnetization transfer and inversion recovery, has been used to produce a 1-dimensional rate profile map of steady-state enzyme activity. Large differences in the flux from phosphocreatine (PCr) to ATP have been discovered between volumes of human brain consisting of predominantly gray (2.0 cm) and white (4.5 cm) matter. The concentration of PCr changes slightly (2.0 cm = 5.20 +/- 0.45 mmol.l-1, 4.5 cm = 4.63 +/- 0.31 mmol.l-1), while the ATP concentration remains within limits (3.30 +/- 0.4 mmol.l-1). No change in pHi was detected between the two regions in normal volunteers (n = 6). The forward rate constant of the PCr----ATP reaction in regions of predominantly gray matter (0.30 +/- 0.04 s-1) was twice that of white matter (0.16 +/- 0.02 s-1) in vivo. PMID:2629743
Cadoux-Hudson, T A; Blackledge, M J; Radda, G K
This book provides an introduction to the current scientific understanding of the human brain and its processes. Chapter 1, "At the Edge of a Major Transformation," is an introduction to the field. Chapter 2, "How Our Brain Organizes Itself on the Cellular and Systems Levels," covers what body/brain cellular systems do, how cells process units of…
Eight normal human brain autopsy samples were analyzed for Na, K, P, Ca, Mg, Si, Cr, Cu, Ni, Zn, Fe, Al, Cd, Pb and As in 12 regions of brain (frontal cerebrum, temporal cerebrum, parietal cerebrum, somatosensory cortex, occipital cerebrum, cerebellum, mid-brain, pons, hypothalamus, thalamus, hippocampus and medulla oblongata) using inductively coupled plasma atomic emission spectrometry (ICPAES). The distribution of
M. T. Rajan; K. S. Jagannatha Rao; B. M. Mamatha; R. V. Rao; P. Shanmugavelu; Rani. B. Menon; M. V. Pavithran
Paragonimus mexicanus is the causal agent of human paragonimiasis in several countries of the Americas. It is considered to be the only species of the genus present in Mexico, where it is responsible for human infection. Through the investigation of P. mexicanus specimens from several places throughout Mexico, we provide morphological, molecular and geographical evidence that strongly suggests the presence of at least three species from this genus in Mexico. These results raise questions regarding the diagnosis, treatment, prophylaxis and control of human paragonimiasis in Mexico. We also provide a brief discussion regarding biodiversity inventories and the convenience of providing molecular and morphological information in biodiversity studies. PMID:23530893
López-Caballero, J; Oceguera-Figueroa, A; León-Règagnon, V
Neuropathologic studies of AIDS patients have shown that brain capillary endothelial cells are a cellular target for human immunodeficiency virus (HIV) in vivo. We have established in vitro cultures of primary human brain capillary endothelial (HBCE) cells. Using this model system, we have shown a significant HIV infection of HBCE cells that is productive yet noncytopathic. The infection is mediated
Ashlee V. Moses; Floyd E. Bloom; C. David Pauza; Jay A. Nelson
Dopamine plays an important role in several brain functions and is involved in the pathogenesis of several psychiatric and neurological disorders. Neuroimaging techniques such as positron emission tomography allow us to quantify dopaminergic activity in the living human brain. Combining these with brain stimulation techniques offers us the unique opportunity to tackle questions regarding region-specific neurochemical activity. Such studies may aid clinicians and scientists to disentangle neural circuitries within the human brain and thereby help them to understand the underlying mechanisms of a given function in relation to brain diseases. Furthermore, it may also aid the development of alternative treatment approaches for various neurological and psychiatric conditions.
Ko, Ji Hyun; Strafella, Antonio P.
Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both.
Herculano-Houzel, Suzana; Kaas, Jon H.
Aerosol therapy protocols could be improved if inhaled pharmacologic drugs were selectively deposited within the human lung. he targeted delivery to specific sites, such as receptors and sensitive airway cells, would enhance the efficacies of airborne pharmaceuticals. he high res...
Success rates with IVF have improved remarkably since the procedure was first established for clinical use with the first successful birth in 1978. The main goals today are to perform single-embryo transfer in order to prevent multiple pregnancies and achieve higher overall pregnancy rates. However, the ability to identify the most viable embryo in a cohort remains a challenge despite the numerous scoring systems currently in use. Clinicians still depend on developmental rate and morphological assessment using light microscopy as the first-line approach for embryo selection. Active research in the field involves developing non-invasive methods for scoring embryos and ranking them according to their ability to implant and give rise to a healthy birth. Current attention is particularly being focused on time-lapse evaluation. Available data from preliminary studies indicate that these systems are safe;prospective data now need to be collected to determine whether these methods do improve implantation rates. This review gives brief consideration to the use of morphological evaluations in assisted reproduction treatment, discusses the types of embryo scoring,digital imaging and biometric approaches currently in use and comments on future developments for embryo evaluation. PMID:23352813
Machtinger, Ronit; Racowsky, Catherine
Complex cognitive functions are widely recognized to be the result of a number of brain regions working together as large-scale networks. Recently, complex network analysis has been used to characterize various structural properties of the large-scale network organization of the brain. For example, the human brain has been found to have a modular architecture i.e., regions within the network form communities (modules) with more connections between regions within the community compared to regions outside it. The aim of this study was to examine the modular and overlapping modular architecture of the brain networks using complex network analysis. We also examined the association between neighborhood level deprivation and brain network structure—modularity and gray nodes. We compared network structure derived from anatomical MRI scans of 42 middle-aged neurologically healthy men from the least (LD) and the most deprived (MD) neighborhoods of Glasgow with their corresponding random networks. Cortical morphological covariance networks were constructed from the cortical thickness derived from the MRI scans of the brain. For a given modularity threshold, networks derived from the MD group showed similar number of modules compared to their corresponding random networks, while networks derived from the LD group had more modules compared to their corresponding random networks. The MD group also had fewer gray nodes—a measure of overlapping modular structure. These results suggest that apparent structural difference in brain networks may be driven by differences in cortical thicknesses between groups. This demonstrates a structural organization that is consistent with a system that is less robust and less efficient in information processing. These findings provide some evidence of the relationship between socioeconomic deprivation and brain network topology.
Krishnadas, Rajeev; Kim, Jongrae; McLean, John; Batty, G. David; McLean, Jennifer S.; Millar, Keith; Packard, Chris J.; Cavanagh, Jonathan
The cerebellum involves diverse functions from motor coordination to higher cognitive functions. Impairment of the cerebellum can cause ataxia and cerebellar cognitive affective syndrome. Multiple system atrophy of the cerebellar type (MSA-C) is a neurodegenerative disorder with atrophy of medullo-ponto-cerebellar (MPC) white matter (WM). To understand the role of the cerebellum from the perspective of the local structure to the global function in the presence of MPC WM degeneration, we acquired T1-weighted and diffusion tensor images for 17 patients with MSA-C and 19 normal controls. We concurrently used the measures of local morphology, including MPC WM volume and inner surface area, and properties of global network organization based on graph theory for the MSA-C and control groups. The results showed that MPC WM degeneration caused the destruction of cerebello-ponto-cerebral loops, resulting in reduced communication efficiency between regions in the whole-brain network. In addition, the sulcal area of the inner cortical surface in the cerebellum decreased linearly with the MPC WM volume, and the inferoposterior lobe exhibited a steeper atrophy rate than that of vermis regions. We concluded that the integrity of MPC WM is critical in sustaining the local morphology and the global functions of the whole-brain fiber network. PMID:23636223
Lu, Chia-Feng; Wang, Po-Shan; Lao, Yuan-Lin; Wu, Hsiu-Mei; Soong, Bing-Wen; Wu, Yu-Te
Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM) and then conducted three-way comparisons among (i) mouse, OWM, and human,
Hurng-Yi Wang; Huan-Chieh Chien; Naoki Osada; Katsuyuki Hashimoto; Sumio Sugano; Takashi Gojobori; Chen-Kung Chou; Shih-Feng Tsai; Chung-I Wu; C.-K. James Shen
Magnetic Amplifying Magneto-Optical System (MAMMOS) shows human brain like memory behavior. Magnetic field and laser power have threshold to recover the stored memory like the human response of remembering. MAMMOS also has a feature to amplify very small ...
N. Ota H. Awano M. Tani S. Imai
Platinum nanoparticles (NP-Pt) are noble metal nanoparticles with unique physiochemical properties that have recently elicited much interest in medical research. However, we still know little about their toxicity and influence on general health. We investigated effects of NP-Pt on the growth and development of the chicken embryo model with emphasis on brain tissue micro- and ultrastructure. The embryos were administered solutions of NP-Pt injected in ovo at concentrations from 1 to 20 ?g/ml. The results demonstrate that NP-Pt did not affect the growth and development of the embryos; however, they induced apoptosis and decreased the number of proliferating cells in the brain tissue. These preliminary results indicate that properties of NP-Pt might be utilized in brain cancer therapy, but potential toxic side effects must be elucidated in extensive follow-up research.
Prasek, Marta; Sawosz, Ewa; Jaworski, Slawomir; Grodzik, Marta; Ostaszewska, Teresa; Kamaszewski, Maciej; Wierzbicki, Mateusz; Chwalibog, Andre
As a group, people with the sex chromosome aneuploidy 49,XXXXY have characteristic physical and cognitive/behavioral tendencies, although there is high individual variation. In this study we use magnetic resonance imaging (MRI) to examine brain morphometry in 14 youth with 49,XXXXY compared to 42 age-matched healthy controls. Total brain size was significantly smaller (t=9.0, p<.001), and rates of brain abnormalities such as colpocephaly, plagiocephaly, periventricular cysts, and minor craniofacial abnormalities were significantly increased. White matter lesions were identified in 50% of subjects, supporting the inclusion of 49,XXXXY in the differential diagnosis of small multifocal white matter lesions. Further evidence of abnormal development of white matter was provided by the smaller cross sectional area of the corpus callosum. These results suggest that increased dosage of genes on the X chromosome has adverse effects on white matter development. PMID:23667827
Blumenthal, Jonathan D; Baker, Eva H; Lee, Nancy Raitano; Wade, Benjamin; Clasen, Liv S; Lenroot, Rhoshel K; Giedd, Jay N
The gross anatomical features of human cervical vertebrae during the fetal-neonatal period were investigated in order to develop morphological standards for the individual ossification centres for use in forensic and anthropological osteology. It was found that the morphology of the cervical vertebral arches and the centra cannot be used for the determination of fetal age although the dens of the axis displays some developmental differences which may be useful for the determination of fetal maturity.
CASTELLANA, C.; KOSA, F.
Morphological observation and measurements of endocasts have played a vital role in research on the evolution of the human brain. However, endocasts have never been used to investigate how the human brain has evolved since the Neolithic period. We investigated the evolution of the human brain during the Holocene by comparing virtual endocasts from Beiqian site (a Neolithic Chinese site) and a sample of Chinese modern-day humans. Standardized measurements and indices were taken to provide quantification of the overall endocast shape, including the length, breadth, height, frontal breadth, and the ratio of frontal breadth to breadth, as well as the cranial capacity. We found that the height of the endocasts and cranial capacity have decreased between our two samples, whereas the frontal breadth and sexual dimorphism have increased. We argue that these changes can be caused by random genetic mutation and epigenetic change in response to changes in the environment. Am J Phys Anthropol 154:94-103, 2014. © 2014 Wiley Periodicals, Inc. PMID:24470191
Liu, Chao; Tang, Yuchun; Ge, Haitao; Wang, Fen; Sun, Huafu; Meng, Haiwei; Wang, Shaoyu; Xu, Junhai; Fan, Rong; Fan, Lingzhong; Zhang, Zhonghe; Shan, Tao; Yuan, Hongtu; Zhan, Jinfeng; Yu, Qiaowen; Ge, Xinting; Tang, Haiyan; Leng, Yuan; Ding, Shihai; Liu, Shuwei
The immunocytochemical expression of the antigen reacting with the monoclonal antibody Ki-67 (Ki-67 positivity) was investigated in 50 imprint preparations from human brain tumours. Data were related to tumour proliferative activity, as determined from in vivo bromodeoxyuridine (BrdU) incorporation (BrdU-labelling index, BrdU-LI) and histology. The percentage of Ki-67-positive cells was greater than the corresponding BrdU-LI value in all tumours, and the differences in Ki-67 positivity among tumour subtypes paralleled the BrdU-LI differences. Both the BrdU-LI and the percentage of Ki-67 positive cells were significantly greater (P less than 0.005) in the group of clinically aggressive adult tumours, histologically identified as anaplastic astrocytomas and glioblastomas, than in the less aggressive ones (oligodendroglioma, meningiomas, schwannomas, pituitary adenomas, dermoid cyst) and in the cerebral metastatic localizations. These data suggest that Ki-67 positivity, which is easily evaluated with immunocytochemistry, is related to the proliferative activity of brain tumours and that this parameter is endowed with clinical significance. PMID:2275874
Girino, M; Riccardi, A; Danova, M; Gaetani, P; Butti, G; Giordano, M; Cuomo, A
Two hundred years ago, Giovanni Aldini published a highly influential book that reported experiments in which the principles of Luigi Galvani (animal electricity) and Alessandro Volta (bimetallic electricity) were used together for the first time. Aldini was born in Bologna in 1762 and graduated in physics at the University of his native town in 1782. As nephew and assistant of Galvani, he actively participated in a series of crucial experiments with frog's muscles that led to the idea that electricity was the long-sought vital force coursing from brain to muscles. Aldini became professor of experimental physics at the University of Bologna in 1798. He traveled extensively throughout Europe, spending much time defending the concept of his discreet uncle against the incessant attacks of Volta, who did not believe in animal electricity. Aldini used Volta's bimetallic pile to apply electric current to dismembered bodies of animals and humans; these spectacular galvanic reanimation experiments made a strong and enduring impression on his contemporaries. Aldini also treated patients with personality disorders and reported complete rehabilitation following transcranial administration of electric current. Aldini's work laid the ground for the development of various forms of electrotherapy that were heavily used later in the 19th century. Even today, deep brain stimulation, a procedure currently employed to relieve patients with motor or behavioral disorders, owes much to Aldini and galvanism. In recognition of his merits, Aldini was made a knight of the Iron Crown and a councillor of state at Milan, where he died in 1834. PMID:15595271
The morphological structure of words, in terms of their stem morphemes and affixes, could influence word access and representation in lexical memory. Three experiments were carried out to explore the attributes of event-related potentials evoked by different types of priming. Morphological priming, with pairs of words related by their stem (hijo/hija [ son/ daughter]), produced a sustained attenuation (and even a tendency to positivity) of the N400 shown by unrelated words across the three experiments. Homographic priming (Experiment 1), using pairs of words with a superficially similar stem, but without morphological or semantic relation (foco/foca [floodlight/seal]), produced an initial attenuation similar to the morphological pairs, but which rapidly tended to form a delayed N400, due to the impossibility of integration. However, orthographic priming (rasa/rana [flat/frog]) in Experiment 2 does not produce attenuation of the N400 but an effect similar to that of unrelated pairs. Experiment 3 shows that synonyms advance more slowly than morphological pairs to meaning coherence, but finally produce a more positive peak around 600 msec. PMID:15165350
Domínguez, Alberto; de Vega, Manuel; Barber, Horacio
This study deals with the appearance, function and pathophysiological action of the lingual venous valve in the design of surgical tongue flaps and in analyzing inspection of the tongue. Thirty two adult cadavers were studied, of which 7 were corrosive cast specimens. The lingual v. is well supplied with venous valves which may be divided into 3 types morphologically: hemispherical, spherical, and hanging spherical. Venous valves are classified according to their structures: bivalves, monovalves, and venous cristae. The abundant venous valves of the tongue effectively prevent reflux of blood. Various factors that influence venous blood reflux in the head and neck can be observed, analysed and judged by inspection of the tongue; the design of the pedicle and the anastomotic position of tongue flap should comply with the positions and orientations of its venous valves. PMID:9706674
Shangkuan, H; Xinghai, W; Shizhen, Z; Zengxing, W; Shiying, J
Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic ?-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of ?- and ?-cells that resulted in an altered ?-cell-to-?-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of ?-cells are potential contributors to the ?-cell compensatory response to insulin resistance in the absence of overt diabetes. PMID:24215793
Mezza, Teresa; Muscogiuri, Giovanna; Sorice, Gian Pio; Clemente, Gennaro; Hu, Jiang; Pontecorvi, Alfredo; Holst, Jens J; Giaccari, Andrea; Kulkarni, Rohit N
Neuroimaging studies have provided important information regarding how and where pitch is coded and processed in the human brain. Recordings of the frequency-following response (FFR), an electrophysiological measure of neural temporal coding in the brainstem, have shown that the precision of temporal pitch information is dependent on linguistic and musical experience, and can even be modified by short-term training. However, the FFR does not seem to represent the output of a pitch extraction process, and this raises questions regarding how the peripheral neural signal is processed to produce a unified sensation. Since stimuli with a wide variety of spectral and binaural characteristics can produce the same pitch, it has been suggested that there is a place in the ascending auditory pathway at which the representations converge. There is evidence from many different human neuroimaging studies that certain areas of auditory cortex are specifically sensitive to pitch, although the location is still a matter of debate. Taken together, the results suggest that the initial temporal pitch code in the auditory periphery is converted to a code based on neural firing rate in the brainstem. In the upper brainstem or auditory cortex, the information from the individual harmonics of complex tones is combined to form a general representation of pitch. This article is part of a Special Issue entitled Human Auditory Neuroimaging. PMID:23938209
Plack, Christopher J; Barker, Daphne; Hall, Deborah A
Craniofacial integration is prevalent in anatomical modernity research. Little investigation has been done on mandibular integration. Integration patterns were quantified in a longitudinal modern human sample of mandibles. This integration pattern is one of modularization between the alveolar and muscle attachment regions, but with age-specific differences. The ascending ramus and nonalveolar portions of the corpus remain integrated throughout ontogeny. The alveolar region is dynamic, becoming modularized according to the needs of the mandible at a particular developmental stage. Early in ontogeny, this modularity reflects the need for space for the developing dentition; later, modularity is more reflective of mastication. The overall pattern of modern human mandibular integration follows the integration pattern seen in other mammals, including chimpanzees. Given the differences in craniofacial integration patterns between humans and chimpanzees, but the similarities in mandibular integration, it is likely that the mandible has played the more passive role in hominin skull evolution.
Polanski, Joshua M.
BACKGROUND: The multiple drug resistance protein (MDR1\\/P-glycoprotein) is overexpressed in glia and blood-brain barrier (BBB) endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs) can act as substrates for MDR1, the enhanced expression\\/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. METHODS: Human drug resistant epileptic brain tissues
Nicola Marchi; Kerri L Hallene; Kelly M Kight; Luca Cucullo; Gabriel Moddel; William Bingaman; Gabriele Dini; Annamaria Vezzani; Damir Janigro
CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed
Sharon Miksys; Caryn Lerman; Peter G. Shields; Deborah C. Mash; Rachel F. Tyndale
A well-established navigation method is one of the key conditions for successful brain surgery: it should be accurate, safe and online operable. Recent research shows that optical coherence tomography (OCT) is a potential solution for this application by providing a high resolution and small probe dimension. In this study a fiber-based spectral-domain OCT system utilizing a super-luminescent-diode with the center wavelength of 840 nm providing 14.5 ?m axial resolution was used. A composite 125 ?m diameter detecting probe with a gradient index (GRIN) fiber fused to a single mode fiber was employed. Signals were reconstructed into grayscale images by horizontally aligning A-scans from the same trajectory with different depths. The reconstructed images can display brain morphology along the entire trajectory. For scans of typical white matter, the signals showed a higher reflection of light intensity with lower penetration depth as well as a steeper attenuation rate compared to the scans typical for gray matter. Micro-structures such as axon bundles (70 ?m) in the caudate nucleus are visible in the reconstructed images. This study explores the potential of OCT to be a navigation modality in brain surgery.
Xie, Yijing; Bonin, Tim; Löffler, Susanne; Hüttmann, Gereon; Tronnier, Volker; Hofmann, Ulrich G.
BrainResonance is an Electroencephalogram (EEG)-based system proposed to explore the feasibility of using EEG signals for human interaction. EEG signals that measure human brain activities were captured from two users simultaneously in real- time. The correlation values of their EEG alpha and beta rhythms were computed and used to drive a visual feedback system that was in the form of
Background: Using human brain microvascular endothelial cells (HBMECs) as an in vitro model for how African trypanosomes cross the human blood-brain barrier (BBB) we recently reported that the parasites cross the BBB by generating calcium activation signals in HBMECs through the activity of parasite cysteine proteases, particularly cathepsin L (brucipain). In the current study, we examined the possible role of
Dennis J. Grab; Jose C. Garcia-Garcia; Olga V. Nikolskaia; Yuri V. Kim; Amanda Brown; Carlos A. Pardo; Yongqing Zhang; Kevin G. Becker; Brenda A. Wilson; Julio Scharfstein; J. Stephen Dumler
BACKGROUND & AIMS: Brain loci that process human esophageal sensation remain unidentified. The aim of this study was to identify the brain loci that process nonpainful and painful human esophageal sensation. METHODS: In 8 healthy subjects (7 men; age range, 24-47 years), distal esophageal stimulation was performed by repeatedly inflating a balloon at volumes that produced either no sensation, definite
Q Aziz; JL Andersson; S Valind; A Sundin; S Hamdy; AK Jones; ER Foster; B Langstrom; DG Thompson
Congenital human cytomegalovirus (HCMV) infection is the most frequent infectious cause of birth defects, primarily neurological disorders. Neural progenitor/stem cells (NPCs) are the major cell type in the subventricular zone and are susceptible to HCMV infection. In culture, the differentiation status of NPCs may change with passage, which in turn may alter susceptibility to virus infection. Previously, only early-passage (i.e., prior to passage 9) NPCs were studied and shown to be permissive to HCMV infection. In this study, NPC cultures derived at different gestational ages were evaluated after short (passages 3 to 6) and extended (passages 11 to 20) in vitro passages for biological and virological parameters (i.e., cell morphology, expression of NPC markers and HCMV receptors, viral entry efficiency, viral gene expression, virus-induced cytopathic effect, and release of infectious progeny). These parameters were not significantly influenced by the gestational age of the source tissues. However, extended-passage cultures showed evidence of initiation of differentiation, increased viral entry, and more efficient production of infectious progeny. These results confirm that NPCs are fully permissive for HCMV infection and that extended-passage NPCs initiate differentiation and are more permissive for HCMV infection. Later-passage NPCs being differentiated and more permissive for HCMV infection suggest that HCMV infection in fetal brain may cause more neural cell loss and give rise to severe neurological disabilities with advancing brain development.
Pan, Xing; Li, Xiao-Jun; Liu, Xi-Juan; Yuan, Hui; Li, Jia-Fu; Duan, Ying-Liang; Ye, Han-Qing; Fu, Ya-Ru; Qiao, Guan-Hua; Wu, Cong-Cong; Yang, Bo; Tian, Xiao-Hui; Hu, Kang-Hong; Miao, Ling-Feng; Chen, Xiao-Ling; Zheng, Jun; Rayner, Simon; Schwartz, Philip H.; Britt, William J.
Purpose The aim of the study was to examine the different morphometric variations of the human mandibles, comparing between males\\u000a and females in dentate and edentulous mandibles.\\u000a \\u000a \\u000a \\u000a \\u000a Methods Eighty adult human dry mandibles were studied. Thirty-two variations were evaluated according to the presence and absence\\u000a of teeth. Kolmogorov–Smirnov test was performed to evaluate the normal distribution of the morphometric variables. Levene\\u000a test
Bruno Ramos Chrcanovic; Mauro Henrique Nogueira Guimarães Abreu; Antônio Luís Neto Custódio
To make decisions based on the value of different options, we often have to combine different sources of probabilistic evidence. For example, when shopping for strawberries on a fruit stand, one uses their color and size to infer—with some uncertainty—which strawberries taste best. Despite much progress in understanding the neural underpinnings of value-based decision making in humans, it remains unclear how the brain represents different sources of probabilistic evidence and how they are used to compute value signals needed to drive the decision. Here, we use a visual probabilistic categorization task to show that regions in ventral temporal cortex encode probabilistic evidence for different decision alternatives, while ventromedial prefrontal cortex integrates information from these regions into a value signal using a difference-based comparator operation.
Philiastides, Marios G.; Biele, Guido; Heekeren, Hauke R.
A procedure to characterize firing patterns of neuron spikes from the human brain, in both temporal domain and the frequency domain, is presented. The combination of multitaper spectral estimation and the polynomial curve-fitting method is employed to transform the firing patterns to the frequency domain. To generate temporal shapes, eight local maxima are smoothly connected by cubic spline interpolation. We then used a rotated principal component analysis, which removes the orthogonality constraints of traditional PCA, to extract common firing patterns as templates from around 4100 neuron spike signals. Dynamic time warping was used to assign each neuron firings into the closest template without shift error. This technique can be utilized for finding firing similarities in neuroscience applications and in development of a query system. PMID:17271330
Cho, Hansang; Corina, D; Ojemann, G A; Shapiro, Linda
Musicians recognize pitch as having two dimensions. On the keyboard, these are illustrated by the octave and the cycle of notes within the octave. In perception, these dimensions are referred to as pitch height and pitch chroma, respectively. Pitch chroma provides a basis for presenting acoustic patterns (melodies) that do not depend on the particular sound source. In contrast, pitch height provides a basis for segregation of notes into streams to separate sound sources. This paper reports a functional magnetic resonance experiment designed to search for distinct mappings of these two types of pitch change in the human brain. The results show that chroma change is specifically represented anterior to primary auditory cortex, whereas height change is specifically represented posterior to primary auditory cortex. We propose that tracking of acoustic information streams occurs in anterior auditory areas, whereas the segregation of sound objects (a crucial aspect of auditory scene analysis) depends on posterior areas.
Warren, J. D.; Uppenkamp, S.; Patterson, R. D.; Griffiths, T. D.
Dynamic shim updating (DSU) of the zero- to second-order spherical harmonic field terms has previously been shown to improve the magnetic field homogeneity in the human brain at 4 Tesla. The increased magnetic field inhomogeneity at 7 Tesla can benefit from inclusion of third-order shims during DSU. However, pulsed higher-order shims can generate a multitude of temporally varying magnetic fields arising from eddy-currents that can strongly degrade the magnetic field homogeneity. The first realization of zero- to third-order DSU with full preemphasis and B0 compensation enabled improved shimming of the human brain at 7 Tesla not only in comparison with global (i.e. static) shimming, but also when compared to state-of-the-art zero- to second-order DSU. Temporal shim-to-shim interactions were measured for each of the 16 zero- to third-order shim coils along 1D column projections on a spherical phantom. The decomposition into up to 3 exponentials allowed full preemphasis and B0 compensation of all 16 shims covering 67 potential shim-to-shim interactions. Despite the significant improvements achievable with DSU, the magnetic field homogeneity is still not perfect even when updating all zero- through third-order shims. This is because DSU is still inherently limited by the shallowness of the low order spherical harmonic fields and their inability to compensate the higher-order inhomogeneities encountered in vivo. However, DSU maximizes the usefulness of conventional shim coil systems and provides magnetic field homogeneity that is adequate for a wide range of applications.
Juchem, Christoph; Nixon, Terence W.; Diduch, Piotr; Rothman, Douglas L.; Starewicz, Piotr; de Graaf, Robin A.
The ability to perceive causality is a central human ability constructed from elemental spatial and temporal information present in the environment. Although the nature of causality has captivated philosophers and scientists since antiquity, the neural correlates of causality remain poorly understood. In the present study, we used functional magnetic resonance imaging (fMRI) to generate hypotheses for candidate brain regions related to component processes important for perceptual causality in the human brain: elemental space perception, elemental time perception, and decision-making (Experiment 1; n=16). We then used transcranial direct current stimulation (tDCS) to test neural hypotheses generated from the fMRI experiment (Experiment 2; n=16). In both experiments, participants judged causality in billiard-ball style launching events; a blue ball approaches and contacts a red ball. Spatial and temporal contributions to causal perception were assessed by parametrically varying the spatial linearity and the temporal delays of the movement of the balls. Experiment 1 demonstrated unique patterns of activation correlated with spatial, temporal, and decision-making components of causality perception. Using tDCS, we then tested hypotheses for the specific roles of the parietal and frontal cortices found in the fMRI experiment. Parietal stimulation only decreased participants' perception of causality based on spatial violations, while frontal stimulation made participants less likely to perceive causality based on violations of space and time. Converging results from fMRI and tDCS indicate that parietal cortices contribute to causal perception because of their specific role in processing spatial relations, while the frontal cortices contribute more generally, consistent with their role in decision-making. PMID:24561228
Woods, Adam J; Hamilton, Roy H; Kranjec, Alexander; Minhaus, Preet; Bikson, Marom; Yu, Jonathan; Chatterjee, Anjan
Recent interest in human brain connectivity has led to the application of graph theoretical analysis to human brain structural networks, in particular white matter connectivity inferred from diffusion imaging and fiber tractography. While these methods have been used to study a variety of patient populations, there has been less examination of the reproducibility of these methods. A number of tractography algorithms exist and many of these are known to be sensitive to user-selected parameters. The methods used to derive a connectivity matrix from fiber tractography output may also influence the resulting graph metrics. Here we examine how these algorithm and parameter choices influence the reproducibility of proposed graph metrics on a publicly available test-retest dataset consisting of 21 healthy adults. The dice coefficient is used to examine topological similarity of constant density subgraphs both within and between subjects. Seven graph metrics are examined here: mean clustering coefficient, characteristic path length, largest connected component size, assortativity, global efficiency, local efficiency, and rich club coefficient. The reproducibility of these network summary measures is examined using the intraclass correlation coefficient (ICC). Graph curves are created by treating the graph metrics as functions of a parameter such as graph density. Functional data analysis techniques are used to examine differences in graph measures that result from the choice of fiber tracking algorithm. The graph metrics consistently showed good levels of reproducibility as measured with ICC, with the exception of some instability at low graph density levels. The global and local efficiency measures were the most robust to the choice of fiber tracking algorithm. PMID:24847245
Duda, Jeffrey T; Cook, Philip A; Gee, James C
Recent interest in human brain connectivity has led to the application of graph theoretical analysis to human brain structural networks, in particular white matter connectivity inferred from diffusion imaging and fiber tractography. While these methods have been used to study a variety of patient populations, there has been less examination of the reproducibility of these methods. A number of tractography algorithms exist and many of these are known to be sensitive to user-selected parameters. The methods used to derive a connectivity matrix from fiber tractography output may also influence the resulting graph metrics. Here we examine how these algorithm and parameter choices influence the reproducibility of proposed graph metrics on a publicly available test-retest dataset consisting of 21 healthy adults. The dice coefficient is used to examine topological similarity of constant density subgraphs both within and between subjects. Seven graph metrics are examined here: mean clustering coefficient, characteristic path length, largest connected component size, assortativity, global efficiency, local efficiency, and rich club coefficient. The reproducibility of these network summary measures is examined using the intraclass correlation coefficient (ICC). Graph curves are created by treating the graph metrics as functions of a parameter such as graph density. Functional data analysis techniques are used to examine differences in graph measures that result from the choice of fiber tracking algorithm. The graph metrics consistently showed good levels of reproducibility as measured with ICC, with the exception of some instability at low graph density levels. The global and local efficiency measures were the most robust to the choice of fiber tracking algorithm.
Duda, Jeffrey T.; Cook, Philip A.; Gee, James C.
The mammalian target of rapamycin (mTOR) assembles into two distinct multi-protein complexes called mTORC1 and mTORC2. Whereas mTORC1 is known to regulate cell and organismal growth, the role of mTORC2 is less understood. We describe two mouse lines that are devoid of the mTORC2 component rictor in the entire central nervous system or in Purkinje cells. In both lines neurons were smaller and their morphology and function were strongly affected. The phenotypes were accompanied by loss of activation of Akt, PKC, and SGK1 without effects on mTORC1 activity. The striking decrease in the activation and expression of several PKC isoforms, the subsequent loss of activation of GAP-43 and MARCKS, and the established role of PKCs in spinocerebellar ataxia and in shaping the actin cytoskeleton strongly suggest that the morphological deficits observed in rictor-deficient neurons are mediated by PKCs. Together our experiments show that mTORC2 has a particularly important role in the brain and that it affects size, morphology, and function of neurons.
Thomanetz, Venus; Angliker, Nico; Cloetta, Dimitri; Lustenberger, Regula M.; Schweighauser, Manuel; Oliveri, Filippo; Suzuki, Noboru
The aim of this study has been to characterize adult human somatic periodontium-derived stem cells (PDSCS) isolated from human periodontium and to follow their differentiation after cell culture. PDSCS were isolated from human periodontal tissue and cultured as spheres in serum-free medium. After 10 days the primary spheres were dissociated and the secondary spheres sub-cultured for another 1-2 weeks. Cells from different time points were analyzed, and immunohistochemical and electron microscopic investigations carried out. Histological analysis showed differentiation of spheres deriving from the PDSCS with central production of extracellular matrix beginning 3 days after sub-culturing. Isolated PDSCS developed pseudopodia which contained actin. Tubulin was found in the central portion of the cells. Pseudopodia between different cells anastomosed, indicating intercellular transport. Immunostaining for osteopontin demonstrated a positive reaction in primary spheres and within extracellular matrix vesicles after sub-culturing. In cell culture under serum-free conditions human PDSCS form spheres which are capable of producing extracellular matrix. Further investigations have do be carried out to investigate the capability of these cells to differentiate into osteogenic progenitor cells. PMID:20591640
Arnold, Wolfgang H; Becher, Sebastian; Dannan, A; Widera, Darius; Dittmar, T; Jacob, Monica; Mannherz, Hans Georg; Dittmar, Thomas; Kaltschmidt, B; Kaltschmidt, C; Grimm, Wolf-Dieter
BACKGROUND: Global ubiquitination in human semen has been found to negatively correlate with standard semen parameters, indicating that ubiquitination can be considered a marker of poor semen quality. However, the inclusion of all semen components in the analysis may be misleading on the biological significance of ubiquitination of sperm cells. We have recently demonstrated the variable presence of bodies of
Monica Muratori; Sara Marchiani; Gianni Forti; Elisabetta Baldi
The objective of the project is to perform anatomically correlated high resolution DTI studies and quantitative immunohistochemical analyses of axonal injury in the human brain following traumatic brain injury. The specific aims are Aim (1) To optimize th...
D. L. Brody
SUMMARY Visual commissures of the honeybee brain were investigated by electrophysiologi- cal and histological methods. 1. A newly described serpentine optic commissure (SOC) consists of four neurones each of which has widely extending arborizations in both medullae and lobulae. The cells are monocularly sensitive, the best stimulus being a moving target. 2. Neurones of the posterior optic commissure (POC) connect
HORST HERTEL; SABINE SCHAFER; ULRIKE MARONDE
The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive…
Thomann, Philipp A.; Toro, Pablo; Santos, Vasco Dos; Essig, Marco; Schroder, Johannes
Background: Pathomorphologic brain changes occur- ring as early as first-episode schizophrenia have been ex- tensively described. Longitudinal studies have demon- strated that these changes may be progressive and associated with clinical outcome. This raises the possi- bility that antipsychotics might alter such pathomorpho- logic progression in early-stage schizophrenia. Objective: To test a priori hypotheses that olanzapine- treated patients have less
Jeffrey A. Lieberman; Gary D. Tollefson; Cecil Charles; Robert Zipursky; Tonmoy Sharma; Rene S. Kahn; Richard S. E. Keefe; Alan I. Green; Raquel E. Gur; Joseph McEvoy; Diana Perkins; Robert M. Hamer; Hongbin Gu; Mauricio Tohen
The first isolation in the UK of Balamuthia mandrillaris amoebae from a fatal case of granulomatous amoebic meningoencephalitis is reported. Using primary cultures of human brain microvascular endothelial cells (HBMECs), amoebae were isolated from the brain and cerebrospinal fluid (CSF). The cultures showed a cytopathic effect at 20-28 days, but morphologically identifiable B. mandrillaris amoebae were seen in cleared plaques in subcultures at 45 days. The identification of the organism was later confirmed using PCR on Chelex-treated extracts. Serum taken while the patient was still alive reacted strongly with slide antigen prepared from cultures of the post-mortem isolate, and also with those from a baboon B. mandrillaris strain at 1:10,000 in indirect immunofluorescence, but with Acanthamoeba castellanii (Neff) at 1:160, supporting B. mandrillaris to be the causative agent. If the presence of amoebae in the post-mortem CSF reflects the condition in life, PCR studies on CSF and on biopsies of cutaneous lesions may also be a valuable tool. The role of HBMECs in understanding the interactions of B. mandrillaris with the blood-brain barrier is discussed. PMID:15358823
Jayasekera, Samantha; Sissons, James; Tucker, Julie; Rogers, Claire; Nolder, Debbie; Warhurst, David; Alsam, Selwa; White, Jonathan M L; Higgins, E M; Khan, Naveed Ahmed
Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development.
Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.
Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. PMID:24440528
Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos
A reliable understanding of the nature of causation is the core feature of science. In this paper the concept of top-down causation in the hierarchy of structure and causation is examined in depth. Five different classes of top-down causation are identified and illustrated with real-world examples. They are (1) al gorithmic top-down causation; (2) top-down causation via nonadaptive information control; (3) top-down causation via adaptive selection; (4) top-down causation via adaptive information control; and (5) intelligent top-down causation (i.e., the effect of the human mind on the physical world). Recognizing these forms of causation implies that other kinds of causes than physical and chemical interactions are effective in the real world. Because of the existence of random processes at the bottom, there is sufficient causal slack at the physical level to allow all these kinds of causation to occur without violation of physical causation. That they do indeed occur is indicated by many kinds of evidence. Each such kind of causation takes place in particular in the human brain, as is indicated by specific examples.
Ellis, George F. R.
The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer’s disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based
Philipp A. Thomann; Pablo Toro; Vasco Dos Santos; Marco Essig; Johannes Schröder
\\u000a Previous research has shown that polymorphisms of the apolipoproteins E (APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these\\u000a genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample
J. M. Serra-Grabulosa; P. Salgado-Pineda; C. Junqué; C. Solé-Padullés; P. Moral; A. López-Alomar; T. López; A. López-Guillén; N. Bargalló; J. M. Mercader; I. C. Clemente; D. Bartrés-Faz
Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X-chromosome inactivation and parent-of-origin of the extra X-chromosome have been suggested to influence cognitive function and psychological traits. These issues have not been clarified for KS patients. We studied X-chromosome inactivation pattern, CAG repeat length and parent-of-origin in relation to educational and cohabitation status, personality and autism traits, psychological distress, cognitive function and brain volumes in 73 KS patients and 73 controls. Grey matter (GM) volume of left insula was significantly decreased in KS patients with skewed X-inactivation (z = 5.78) and we observed a borderline significant difference in global brain matter volume where KS patients with skewed X-chromosome inactivation tended to have smaller brains. Skewed X-inactivation, CAG repeat length and parent-of-origin were not correlated with educational and marital status, personality traits, autism traits, and psychological distress, prevalence of depression and anxiety or cognitive function. Interestingly our results regarding brain volumes indicate that X-inactivation has an influence on GM volume in left insula and might also be related to global GM volume, indicating a possible effect of X-linked genes on the development of GM volume in KS patient. Skewed X-inactivation, CAG repeat length and parent-of-origin have no impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov (Clinical trial NCT00999310)). PMID:24865607
Skakkebaek, A; Bojesen, A; Kristensen, M K; Cohen, A; Hougaard, D M; Hertz, J M; Fedder, J; Laurberg, P; Wallentin, M; Ostergaard, J R; Pedersen, A D; Gravholt, C H
The tissue disruption inside the brain after experimental gunshots to the head was investigated with special reference to\\u000a secondary bone missiles and intracranial pressure effects such as cortical contusion and deep intracerebral haemorrhages.\\u000a The evidential value of various examination methods is compared. 9 mm Parabellum ammunition was fired to the temporal region\\u000a of calves (n = 10) from a distance
B. Karger; Z. Puskas; B. Ruwald; K. Teige; G. Schuirer
D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents and basal cerebral blood volume in fronto-hippocampal areas. In addition, we show that both chronic administration of D-Asp and deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO) trigger plastic modifications of neuronal cytoarchitecture in the prefrontal cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive form of synaptic plasticity in adult mouse brains. To translate these findings in humans and consistent with the experiments using Ddo gene targeting in animals, we performed a hierarchical stepwise translational genetic approach. Specifically, we investigated the association of variation in the gene coding for DDO with complex human prefrontal phenotypes. We demonstrate that genetic variation predicting reduced expression of DDO in postmortem human prefrontal cortex is mapped on greater prefrontal gray matter and activity during working memory as measured with MRI. In conclusion our results identify novel NMDAR-dependent effects of D-Asp on plasticity and physiology in rodents, which also map to prefrontal phenotypes in humans. PMID:25072322
Errico, F; Nisticò, R; Di Giorgio, A; Squillace, M; Vitucci, D; Galbusera, A; Piccinin, S; Mango, D; Fazio, L; Middei, S; Trizio, S; Mercuri, N B; Teule, M A; Centonze, D; Gozzi, A; Blasi, G; Bertolino, A; Usiello, A
The neurocognitive and behavioral profile of individuals with 47,XYY is increasingly documented; however, very little is known about the effect of a supernumerary Y-chromosome on brain development. Establishing the neural phenotype associated with 47,XYY may prove valuable in clarifying the role of Y-chromosome gene dosage effects, a potential factor in several neuropsychiatric disorders that show a prevalence bias toward males, including autism spectrum disorders. Here, we investigated brain structure in 10 young boys with 47,XYY and 10 age-matched healthy controls by combining voxel-based morphometry (VBM) and surface-based morphometry (SBM). The VBM results show the existence of altered gray matter volume (GMV) in the insular and parietal regions of 47,XYY relative to controls, changes that were paralleled by extensive modifications in white matter (WM) bilaterally in the frontal and superior parietal lobes. The SBM analyses corroborated these findings and revealed the presence of abnormal surface area and cortical thinning in regions with abnormal GMV and WMV. Overall, these preliminary results demonstrate a significant impact of a supernumerary Y-chromosome on brain development, provide a neural basis for the motor, speech and behavior regulation difficulties associated with 47,XYY and may relate to sexual dimorphism in these areas. PMID:24308542
Lepage, J-F; Hong, D S; Raman, M; Marzelli, M; Roeltgen, D P; Lai, S; Ross, J; Reiss, A L
Astrocytes are the most prevalent type of glial cell in the brain, participating in a variety of diverse functions from regulating cerebral blood flow to controlling synapse formation. Astrocytes and astrocyte-conditioned media are widely used in models of the blood-brain barrier (BBB), however, very little is known about astrocyte culture in 2D. To test the hypothesis that surface coating and soluble factors influence astrocyte morphology in 2D, we quantitatively analyzed the morphology of human fetal derived astrocytes on glass, matrigel, fibronectin, collagen IV, and collagen I, and after the addition soluble factors including platelet-derived growth factor (PDGF), laminin, basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (LIF). Matrigel surface coatings, as well as addition of leukemia inhibitory factor (LIF) to the media, were found to have the strongest effects on 2D astrocyte morphology, and may be important in improving existing BBB models. In addition, the novel set of quantitative parameters proposed in this paper provide a test for determining the influence of compounds on astrocyte morphology, both to screen for new endothelial cell-secreted factors that influence astrocytes, and to determine in a high-throughput way which factors are important for translation to more complex, 3D BBB models.
Levy, Amanda F.; Zayats, Maya; Guerrero-Cazares, Hugo; Quinones-Hinojosa, Alfredo; Searson, Peter C.
This paper suggests that medically the term a 'human being' should be defined by the presence of an active human brain. The brain is the only unique and irreplaceable organ in the human body, as the orchestrator of all organ systems and the seat of personality. Thus, the presence or absence of brain life truly defines the presence or absence of human life in the medical sense. When viewed in this way, human life may be seen as a continuous spectrum between the onset of brain life in utero (eight weeks gestation), until the occurrence of brain death. At any point human tissue or organ systems may be present, but without the presence of a functional human brain, these do not constitute a 'human being', at least in a medical sense. The implications of this theory for various ethical concerns such as in vitro fertilisation and abortion are discussed. This theory is the most consistent possible for the definition of a human being with no contradictions inherent. However, having a good theory of definition of a 'human being' does not necessarily solve the ethical problems discussed herein.
Goldenring, J M
The capillary from the meningeal inner pial lamella play a crucial role in the development and structural organization of the cerebral cortex extrinsic and intrinsic microvascular compartments. Only pial capillaries are capable of perforating through the cortex external glial limiting membrane (EGLM) to enter into the nervous tissue, although incapable of perforating the membrane to exit the brain. Circulatory dynamics and functional demands determine which capillaries become arterial and which capillaries become venous. The perforation of the cortex EGLM by pial capillaries is a complex process characterized by three fundamental stages: (1) pial capillary contact with the EGLM with fusion of vascular and glial basal laminae at the contact site, (2) endothelial cell filopodium penetration through the fussed laminae with the formation of a funnel between them that accompanies it into the nervous tissue while remaining open to the meningeal interstitium and, (3) penetration of the whole capillary carrying the open funnel with it and establishing an extravascular Virchow-Robin Compartment (V-RC) that maintains the perforating vessel extrinsic (outside) the nervous tissue through its entire length. The V-RC is walled internally by the vascular basal lamina and externally by the basal lamina of joined glial cells endfeet. The VRC outer glial wall appear as an extension of the cortex superficial EGLM. All the perforating vessels within the V-RCs constitute the cerebral cortex extrinsic microvascular compartment. These perforating vessels are the only one capable of responding to inflammatory insults. The V-RC remains open (for life) to the meningeal interstitium permitting the exchanges of fluid and of cells between brain and meninges. The V-RC function as the brain sole drainage (prelymphatic) system in both physiological as well as pathological situations. During cortical development, capillaries emerge from the perforating vessels, by endothelial cells growing sprouts analogous to their angiogenesis, entering into their corresponding V-RCs. These new capillaries to enter into the nervous tissue must perforate through the V-RC outer glial wall, a process analogous to the original perforation of the cortex EGLM by pial capillaries. These emerging capillaries are incapable of reentering the V-RCs and/or perforating vessels. As the new capillary enters into the nervous tissue, it becomes surrounded by glial endfeet and carries a single basal lamina (possibly glial). Capillaries emerging from contiguous perforators establish an anastomotic plexus between them, by mechanisms still poorly understood. The capillaries of this anastomotic plexus constitute the cerebral cortex intrinsic microvascular compartment and together constitute the so-called blood-brain-barrier. The intrinsic capillaries are changing and readapting continuously, by both active angiogenesis and reabsorption, to the gray matter neurons developmental and functional needs. The brain intrinsic capillaries are among the most active microvessels of the human body. Unresolved developmental and functional aspects concerning the cerebral cortex intrinsic capillary plexus need to be further investigated.
Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys. PMID:24866127
Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Pieszek, Raik; Sherwood, Chet C; Hof, Patrick R; Ely, John J; Steinhauser, Dirk; Willmitzer, Lothar; Bangsbo, Jens; Hansson, Ola; Call, Josep; Giavalisco, Patrick; Khaitovich, Philipp
Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.
Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Paabo, Svante; Pieszek, Raik; Sherwood, Chet C.; Hof, Patrick R.; Ely, John J.; Steinhauser, Dirk; Willmitzer, Lothar; Bangsbo, Jens; Hansson, Ola; Call, Josep; Giavalisco, Patrick; Khaitovich, Philipp
Type-specific dendritic arborization patterns dictate synaptic connectivity and are fundamental determinants of neuronal function. We exploit the morphological stereotypy and relative simplicity of the Drosophila nervous system to model the diverse dendritic morphologies of individual motor neurons (MNs) to understand underlying principles of synaptic connectivity in a motor circuit. The genetic tractability of Drosophila allows us to label single MNs with green fluorescent protein (GFP) and serially reconstruct identifiable MNs in 3D with confocal microscopy. Our computational approach aims at the robust segmentation of the MN volumes and the simultaneous partitioning into their compartments, namely the soma, axon and dendrites. We use the idea of co-segmentation, where every image along the z-axis (depth) is clustered using information from 'neighboring' depths. As appearance we use a 3D extension of Haar features and for the shape we define an implicit representation of the segmentation domain. PMID:22256136
Tsechpenakis, Gavriil; Gamage, Ruwan Egoda; Kim, Michael D; Chiba, Akira
Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular
Marie-Claire Daou; Thomas W. Smith; N. Scott Litofsky; Chung C. Hsieh; Alonzo H. Ross
The involvement of noncoding RNAs (ncRNAs) in the development of the human brain remains largely unknown. Applying a cloning strategy for detection of intermediate size (50–500 nt) ncRNAs (is-ncRNAs) we have identified 82 novel transcripts in human fetal brain tissue. Most of the novel is-ncRNAs are not well conserved in vertebrates, and several transcripts were only found in primates. Northern blot and microarray analysis indicated considerable variation in expression across human fetal brain development stages and fetal tissues for both novel and known is-ncRNAs. Expression of several of the novel is-ncRNAs was conspicuously absent in one or two brain cancer cell lines, and transient overexpression of some transcripts in cancer cells significantly inhibited cell proliferation. Overall, our results suggest that is-ncRNAs play important roles in the development and tumorigenesis of human brain.
Chen, Xiaoyan; Fan, Zhen; Chen, Runsheng
Normal and diseased human central nervous system (CNS) tissues were studied immunohistochemically by a monoclonal antibody to human macrophages (EBM/11), antisera to glial fibrillary acidic protein (anti-GFAP), and alpha-1-antichymotrypsin (alpha 1-ACT). EBM/11 reacted with brain macrophages located mainly around blood vessels in normal brain; it also reacted with resting microglia in normal brain and with numerous reactive microglia and macrophages in brain tumours and inflammatory lesions. Microglia did not react with anti-GFAP or alpha 1-ACT. An EBM/11 positive phenotype, therefore, is shared by microglia and macrophages and suggests that microglial cells form a specialised part of the mononuclear phagocyte system. Images
Esiri, M M; McGee, J O
The relation between large-scale brain structure and function is an outstanding open problem in neuroscience. We approach this problem by studying the dynamical regime under which realistic spatiotemporal patterns of brain activity emerge from the empirically derived network of human brain neuroanatomical connections. The results show that critical dynamics unfolding on the structural connectivity of the human brain allow the recovery of many key experimental findings obtained from functional magnetic resonance imaging, such as divergence of the correlation length, the anomalous scaling of correlation fluctuations, and the emergence of large-scale resting state networks.
Haimovici, Ariel; Tagliazucchi, Enzo; Balenzuela, Pablo; Chialvo, Dante R.
NMNAT (nicotinamide 5'-mononucleotide adenylyltransferase; EC 126.96.36.199) catalyses the transfer of the adenylyl group from ATP to NMN to form NAD. We have cloned a novel human NMNAT cDNA, designated hNMNAT-2, from human brain. The cDNA contains a 924 bp open reading frame that encodes a 307 amino acid peptide that was expressed as a histidine-patch-containing thioredoxin fusion protein. Expressed hNMNAT-2 shared only 35% amino acid sequence homology with the human NMNAT enzyme (hNMNAT-1), but possessed enzymic activity comparable with hNMNAT-1. Using human genomic databases, hNMNAT-2 was localized to chromosome 1q25 within a 171 kb gene, whereas hNMNAT-1 is on chromosome 1p32-35. Northern blot analysis revealed highly restricted expression of hNMNAT-2 to brain, heart and muscle tissues, which contrasts with the wide tissue expression of hNMNAT-1; different regions of the brain exhibited differential expression of hNMNAT-2. Substitution mutations of either of two invariant residues, His-24 or Trp-92, abolished enzyme activity. Anti-peptide antibody to a unique epitope within hNMNAT-2 was produced, and immunohistochemical analysis of sections of normal adult human pancreas revealed that hNMNAT-2 protein was markedly expressed in the islets of Langerhans. However, the pancreatic exocrine cells exhibited weak expression of hNMNAT-2 protein. Sections of pancreas from insulinoma patients showed strong expression of hNMNAT-2 protein in the insulin-producing tumour cells, whereas acinar cells exhibited relatively low expression of hNMNAT-2 protein. These data suggest that the unique tissue-expression patterns of hNMNAT-2 reflect distinct functions for the isoforms in the regulation of NAD metabolism.
Yalowitz, Joel A; Xiao, Suhong; Biju, Mangatt P; Antony, Asok C; Cummings, Oscar W; Deeg, Mark A; Jayaram, Hiremagalur N
Functional MR imaging (fMRI) enables to detect different activated brain areas according to the performed tasks. However, data are usually evaluated after the experiment, which prohibits intra-experiment optimization or more sophisticated applications such as biofeedback experiments. Using a human-brain-interface (HBI), subjects are able to communicate with external programs, e.g. to navigate through virtual scenes, or to experience and modify their own brain activation. These applications require the real-time analysis and classification of activated brain areas. Our paper presents first results of different strategies for real-time pattern analysis and classification realized within a flexible experiment control system that enables the volunteers to move through a 3D virtual scene in real-time using finger tapping tasks, and alternatively only thought-based tasks.
Moench, Tobias; Hollmann, Maurice; Grzeschik, Ramona; Mueller, Charles; Luetzkendorf, Ralf; Baecke, Sebastian; Luchtmann, Michael; Wagegg, Daniela; Bernarding, Johannes
ATP-depleted human erythrocytes lose their smooth discoid shape and adopt a spiny, crenated form. This shape change coincides with the conversion of phosphatidylinositol-4,5-bisphosphate to phosphatidylinositol and phosphatidic acid to diacylglycerol. Both crenation and lipid dephosphorylation are accelerated by iodoacetamide, and both are reversed by nutrient supplementation. The observed changes in lipid populations should shrink the membrane inner monolayer by 0.6%, consistent with estimates of bilayer imbalance in crenated cells. These observations suggest that metabolic crenation arises from a loss of inner monolayer area secondary to the degradation of phosphatidylinositol-4,5-bisphosphate and phosphatidic acid. A related process, crenation after Ca2+ loading, appears to arise from a loss inositides by a different pathway.
BACKGROUND: Giant binuclear oocytes occur with considerable frequency in human ovaries, but their ultimate fate remains unknown. We report the morphology, cytogenetics and developmental potential of human giant oocytes from patients undergoing assisted reproductive technologies. METHODS AND RESULTS: A total of 44 giant oocytes was collected from patients aged 22-44 years old, with an overall frequency of 0.3% (44\\/14 272
Hanna Balakier; Derek Bouman; Agata Sojecki; Clifford Librach; Jeremy A. Squire
The Golgi method has been used for over a century to describe the general morphology of neurons in the nervous system of different species. The "single-section" Golgi method of Gabbott and Somogyi (1984) and the modifications made by Izzo et al. (1987) are able to produce consistent results. Here, we describe procedures to show cortical and subcortical neurons of human brains immersed in formalin for months or even years. The tissue was sliced with a vibratome, post-fixed in a combination of paraformaldehyde and picric acid in phosphate buffer, followed by osmium tetroxide and potassium dicromate, "sandwiched" between cover slips, and immersed in silver nitrate. The whole procedure takes between 5 and 11 days to achieve good results. The Golgi method has its characteristic pitfalls but, with this procedure, neurons and glia appear well-impregnated, allowing qualitative and quantitative studies under light microscopy. This contribution adds to the basic techniques for the study of human nervous tissue with the same advantages described for the "single-section" Golgi method in other species; it is easy and fast, requires minimal equipment, and provides consistent results. PMID:20347871
Dall'Oglio, Aline; Ferme, Denise; Brusco, Janaína; Moreira, Jorge E; Rasia-Filho, Alberto A
This review covers the relationship between chromosome abnormalities, morphological abnormalities and embryonic development. The baseline of chromosome abnormalities in human embryos produced by assisted reproduction is higher than 50%, regardless of maternal age. While aneuploidy increases with maternal age, abnormalities arising post-meiotically, such as mosaicism, chaoticism, polyploidy and haploidy, have similar incidence in all age groups (about 33%). Post-meiotic abnormalities
Neurons in the human cerebral cortical white matter below motor, visual, auditory and prefrontal orbital areas have been studied with the Golgi method, immunohistochemistry and diaphorase histochemistry. The majority of white matter neurons are pyramidal cells displaying the typical polarized, spiny dendritic system. The morphological variety includes stellate forms as well as bipolar pyramidal cells, and the expression of a
G. Meyer; P. Wahle; A. Castaneyra-Perdomo; R. Ferres-Torres
Magnetic resonance imaging was used to quantify the vocal tract morphology of 129 normal humans, aged 2-25 years. Morphometric data, including midsagittal vocal tract length, shape, and proportions, were collected using computer graphic techniques. There was a significant positive correlation between vocal tract length and body size ~either height or weight!. The data also reveal clear differences in male and
W. Tecumseh Fitch; Jay Giedd
Morphological and sedimentological responses of streams to basin-scale impact have been well documented for intensively agricultural or urban areas. Sensitivity thresholds of streams to modest levels of disturbance, however, are not well understood. This study addresses the influence of forest conversion on streams of the southern Blue Ridge Mountains, a region that has received little attention with respect to human
Katie Price; David S. Leigh
The BCH (BNIP2 and Cdc42GAP Homology) domain-containing protein Bmcc1/Prune2 is highly enriched in the brain and is involved in the regulation of cytoskeleton dynamics and cell survival. However, the molecular mechanisms accounting for these functions are poorly defined. Here, we have identified Bmcc1s, a novel isoform of Bmcc1 predominantly expressed in the mouse brain. In primary cultures of astrocytes and neurons, Bmcc1s localized on intermediate filaments and microtubules and interacted directly with MAP6/STOP, a microtubule-binding protein responsible for microtubule cold stability. Bmcc1s overexpression inhibited MAP6-induced microtubule cold stability by displacing MAP6 away from microtubules. It also resulted in the formation of membrane protrusions for which MAP6 was a necessary cofactor of Bmcc1s. This study identifies Bmcc1s as a new MAP6 interacting protein able to modulate MAP6-induced microtubule cold stability. Moreover, it illustrates a novel mechanism by which Bmcc1 regulates cell morphology. PMID:22523599
Arama, Jessica; Boulay, Anne-Cécile; Bosc, Christophe; Delphin, Christian; Loew, Damarys; Rostaing, Philippe; Amigou, Edwige; Ezan, Pascal; Wingertsmann, Laure; Guillaud, Laurent; Andrieux, Annie; Giaume, Christian; Cohen-Salmon, Martine
The BCH (BNIP2 and Cdc42GAP Homology) domain-containing protein Bmcc1/Prune2 is highly enriched in the brain and is involved in the regulation of cytoskeleton dynamics and cell survival. However, the molecular mechanisms accounting for these functions are poorly defined. Here, we have identified Bmcc1s, a novel isoform of Bmcc1 predominantly expressed in the mouse brain. In primary cultures of astrocytes and neurons, Bmcc1s localized on intermediate filaments and microtubules and interacted directly with MAP6/STOP, a microtubule-binding protein responsible for microtubule cold stability. Bmcc1s overexpression inhibited MAP6-induced microtubule cold stability by displacing MAP6 away from microtubules. It also resulted in the formation of membrane protrusions for which MAP6 was a necessary cofactor of Bmcc1s. This study identifies Bmcc1s as a new MAP6 interacting protein able to modulate MAP6-induced microtubule cold stability. Moreover, it illustrates a novel mechanism by which Bmcc1 regulates cell morphology.
Bosc, Christophe; Delphin, Christian; Loew, Damarys; Rostaing, Philippe; Amigou, Edwige; Ezan, Pascal; Wingertsmann, Laure; Guillaud, Laurent; Andrieux, Annie; Giaume, Christian; Cohen-Salmon, Martine
Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-11C]DHA mostly entered nonbrain organs, with ?0.5% entering the brain. Then, using PET and intravenous [1-11C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [15O]water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate Jin, the product of K*, and the unesterified plasma DHA concentration equaled 3.8 ± 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-11C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease.
Umhau, John C.; Zhou, Weiyin; Carson, Richard E.; Rapoport, Stanley I.; Polozova, Alla; Demar, James; Hussein, Nahed; Bhattacharjee, Abesh K.; Ma, Kaizong; Esposito, Giuseppe; Majchrzak, Sharon; Herscovitch, Peter; Eckelman, William C.; Kurdziel, Karen A.; Salem, Norman
Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [(11)C]harmine, [(11)C]clorgyline, and [(11)C]befloxatone; MAO-B: [(11)C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n=38) and developmental/aging changes (21?hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [(11)C]befloxatone (binding potential (BP), r=0.61, P=0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P<0.01) for [(11)C]harmine (distribution volume, r=0.86), [(11)C]clorgyline (?k3, r=0.82), and [(11)C]deprenyl-D2 (?k3 or modified Patlak slope, r=0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ?2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality. PMID:23403377
Tong, Junchao; Meyer, Jeffrey H; Furukawa, Yoshiaki; Boileau, Isabelle; Chang, Li-Jan; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J
Cognitive neuroscientists increasingly recognize that continued progress in understanding human brain function will require not only the acquisition of new data, but also the synthesis and integration of data across studies and laboratories. Here we review ongoing efforts to develop a more cumulative science of human brain function. We discuss the rationale for an increased focus on formal synthesis of the cognitive neuroscience literature, provide an overview of recently developed tools and platforms designed to facilitate the sharing and integration of neuroimaging data, and conclude with a discussion of several emerging developments that hold even greater promise in advancing the study of human brain function.
Yarkoni, Tal; Poldrack, Russell A.; Van Essen, David C.; Wager, Tor D.
The cervical vertebral column bears or balances the weight of the head supported by the nuchal muscles that partly originate from the cervical vertebrae. The position of the head relative to the vertebral column, and consequently locomotion and posture behavior, could thus be associated with the form of the cervical vertebrae. In spite of this assumption and some empirical indications along these lines, primate vertebral morphologies have been reported to be very similar and not clearly related to locomotion. We therefore study the relationship between the morphology of the first cervical vertebra, the atlas, and the locomotion pattern within primates using a geometric morphometric approach. Our analysis is based on a total of 116 vertebrae of adult Homo sapiens, Gorilla gorilla, Pan troglodytes, Pongo pygmaeus, Hylobates lar, Macaca mulatta, Papio hamadryas, Ateles geoffroyi, and Alouatta palliata. On each atlas, 56 landmarks were digitized and superimposed by Procrustes registration. The resulting shape variables were analyzed by principal component analysis, multivariate regression, and partial least-squares analysis. We found that the nine primate species differ clearly in their atlas morphology and that allometric shape change is distinct between the nonhuman primates and Homo sapiens. We could further identify morphological features that relate to the species' locomotion pattern. Human atlas shape, however, cannot be predicted by an extrapolation of the nonhuman primate model. This implies that either the primate atlas is generalized enough to allow bipedal locomotion or else the human atlas morphology is a unique adaptation different from that in the more orthograde nonhuman primates. PMID:16955497
Manfreda, Evelyn; Mitteroecker, Philipp; Bookstein, Fred L; Schaefer, Katrin
The latent prevalence of a long-lived and common brain parasite, Toxoplasma gondii, explains a statistically significant portion of the variance in aggregate neuroticism among populations, as well as in the ‘neurotic’ cultural dimensions of sex roles and uncertainty avoidance. Spurious or non-causal correlations between aggregate personality and aspects of climate and culture that influence T. gondii transmission could also drive these patterns. A link between culture and T. gondii hypothetically results from a behavioural manipulation that the parasite uses to increase its transmission to the next host in the life cycle: a cat. While latent toxoplasmosis is usually benign, the parasite's subtle effect on individual personality appears to alter the aggregate personality at the population level. Drivers of the geographical variation in the prevalence of this parasite include the effects of climate on the persistence of infectious stages in soil, the cultural practices of food preparation and cats as pets. Some variation in culture, therefore, may ultimately be related to how climate affects the distribution of T. gondii, though the results only explain a fraction of the variation in two of the four cultural dimensions, suggesting that if T. gondii does influence human culture, it is only one among many factors.
Lafferty, Kevin D
The neurochemical organization of the posterior caudate nucleus (CN) (body, gyrus and tail) and putamen (Put) was analyzed in the human brain using adjacent sections stained for acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), enkephalin (ENK), parvalbumin (PV), calbindin (CB) and tyrosine hydroxylase (TH). Striosomes were visualized in all striatal regions but the anterior two thirds of the CN tail. They were highly immunoreactive (-ir) for ENK and LAMP, devoid of PV and AChE staining, and surrounded by a ring of tissue with pale TH- and CB-ir neuropil. In the Put, other rings of tissue completely free of ENK labeling surrounded certain striosomes (clear septa). In the CN body, gyrus and tail some markers revealed gradients and heterogeneities along the dorsoventral and mediolateral axes. A rim of striatal tissue densely stained for ENK and LAMP and poorly labeled for PV was noticeable along the lateral edge of the Put and the dorsolateral sector of the CN body. Our results illustrate a chemical architecture in the posterior striatum that is heterogeneous and slightly different from that found in the more anterior striatum. PMID:17726572
Bernácer, J; Prensa, L; Giménez-Amaya, J M
Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology. Images
Atwood, W J; Berger, J R; Kaderman, R; Tornatore, C S; Major, E O
Repeated processing of the same information is associated with decreased neuronal responses, termed repetition suppression (RS). Although RS effects (i.e., the difference in activity between novel and repeated stimuli) have been demonstrated within several brain regions, such as the medial temporal lobe, their precise neural mechanisms still remain unclear. Here, we used functional magnetic resonance imaging together with psychopharmacology in 48 healthy human subjects, demonstrating that RS effects within the mesolimbic system are differentially modulated by cholinergic and dopaminergic stimulation. The dopamine precursor levodopa (100 mg) attenuated RS within the hippocampus, parahippocampal cortex, and substantia nigra/ventral tegmental area, and the degree of this reduction correlated with recognition memory performance 24 h later. The acetylcholinesterase inhibitor galantamine (8 mg), in contrast, reversed RS into repetition enhancement, showing no relationship to subsequent recognition memory. This suggests that novelty sensitive neural populations of the mesolimbic system can dynamically shift their responses depending on the balance of cholinergic and dopaminergic neurotransmission, and these shifts can influence memory retention. PMID:23307638
Bunzeck, Nico; Guitart-Masip, Marc; Dolan, Raymond J; Duzel, Emrah
Vascular diseases of the human brain are one of the reasons of deaths and people's incapacitation not only in Russia, but also in the world. The danger of an arteriovenous malformation (AVM) is in premature rupture of pathological vessels of an AVM which may cause haemorrhage. Long-term prognosis without surgical treatment is unfavorable. The reduced impact method of AVM treatment is embolization of a malformation which often results in complete obliteration of an AVM. Pre-surgical mathematical modeling of an arteriovenous malformation can help surgeons with an optimal sequence of the operation. During investigations, the simple mathematical model of arteriovenous malformation is developed and calculated, and stationary and non-stationary processes of its embolization are considered. Various sequences of embolization of a malformation are also considered. Calculations were done with approximate steady flow on the basis of balanced equations derived from conservation laws. Depending on pressure difference, a fistula-type AVM should be embolized at first, and then small racemose AVMs are embolized. Obtained results are in good correspondence with neurosurgical AVM practice.
Nadezhda Telegina, Ms; Aleksandr Chupakhin, Mr; Aleksandr Cherevko, Mr
Angiogenesis is an important physiological and pathological process. Bartonella is the only genus of bacteria known to induce pathological angiogenesis in the mammalian host. Bartonella-induced angiogenesis leads to the formation of vascular tumors including verruga peruana and bacillary angiomatosis. The mechanism of Bartonella-induced angiogenesis is not completely understood. Pericytes, along with endothelial cells, play an important role in physiological angiogenesis, and their role in tumor angiogenesis has been extensively studied. Abnormal signaling between endothelial cells and pericytes contributes to tumor angiogenesis and metastasis; however, the role of pericytes in Bartonella-induced angiogenesis is not known. In this study, after infecting human brain vascular pericytes (HBVPs) with Bartonella henselae, we found that these bacteria were able to invade HBVPs and that bacterial infection resulted in decreased pericyte proliferation and increased pericyte production of vascular endothelial growth factor (VEGF) when compared to the uninfected control cells. In the context of pathological angiogenesis, reduced pericyte coverage, accompanied by increased VEGF production, may promote endothelial cell proliferation and the formation of new vessels. PMID:23184416
Varanat, Mrudula; Maggi, Ricardo G; Linder, Keith E; Breitschwerdt, Edward B
In vitro preincubation of brain membranes of aged mice wirh piracetam (0.1–1.0 mmol\\/L) enhanced membrane fluidity, as indicated by decreased anisotropy of the membrane-bound fluorescence probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Piracetam had similar in vitro effects on brain membranes of aged rats and humans, but it did not alter brain membrane fluidity in young mice. Chronic treatment of young and aged rats
Walter E. Müller; Sabrina Koch; Klaus Scheuer; Angelika Rostock; Reni Bartsch
Cognitive processes, such as spatial attention, are thought to rely on extended networks in the human brain. Both clinical data from lesioned patients and fMRI data acquired when healthy subjects perform particular cognitive tasks typically implicate a wide expanse of potentially contributing areas, rather than just a single brain area. Conversely, evidence from more targeted interventions, such as transcranial magnetic stimulation (TMS) or invasive microstimulation of the brain, or selective study of patients with highly focal brain damage, can sometimes indicate that a single brain area may make a key contribution to a particular cognitive process. But this in turn raises questions about how such a brain area may interface with other interconnected areas within a more extended network to support cognitive processes. Here, we provide a brief overview of new approaches that seek to characterise the causal role of particular brain areas within networks of several interacting areas, by measuring the effects of manipulations for a targeted area on function in remote interconnected areas. In human participants, these approaches include concurrent TMS-fMRI and TMS-EEG, as well as combination of the focal lesion method in selected patients with fMRI and/or EEG measures of the functional impact from the lesion on interconnected intact brain areas. Such approaches shed new light on how frontal cortex and parietal cortex modulate sensory areas in the service of attention and cognition, for the normal and damaged human brain.
Driver, Jon; Blankenburg, Felix; Bestmann, Sven
The growth and morphology as well as collagen biosynthesis of human fibroblasts obtained and cultured on sepiolite-collagen complexes have been studied. No differences on cell morphology and growth properties nor collagen synthesis were observed when compared with standard culture substrates. The type I/type III ratio of biosynthesized collagen by fibroblasts cultured on sepiolite-collagen complexes was about 5-6 with no difference when compared to control conditions. This normal behavior was also observed for the type I/type III procollagens. According to these studies the sepiolite-collagen complexes do not modify the studied features of the fibroblasts. PMID:2967297
Olmo, N; Lizarbe, M A; Turnay, J; Müller, K P; Gavilanes, J G
In order to approach the physiopathological mechanism underlying the selective susceptibility of the immature brain to hypoxia-ischemia (HI), we have compared the lesions experimentally induced in postnatal day 7 rats using a model of neonatal stroke with those occurring in human fetal and neonatal brains. We first observed that gray and white matter lesions demonstrated a similar organization (core with
Antoinette Gelot; S. Villapol; Thierry Billette de Villemeur; Sylvain Renolleau; Christiane Charriaut-Marlangue
The teaching brain is a new concept that mirrors the complex, dynamic, and context-dependent nature of the learning brain. In this article, I use the structure of the human nervous system and its sensing, processing, and responding components as a framework for a re-conceptualized teaching system. This teaching system is capable of responses on an…
The purpose of this study was to analyze participants' levels of hemoglobin as they performed arithmetic mental calculations using Optical Topography (OT, helmet type brain-scanning system, also known as Functional Near-Infrared Spectroscopy or fNIRS). A central issue in cognitive neuroscience involves the study of how the human brain encodes and…
The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched
Louis N. Manganas; Xueying Zhang; Yao Li; Raphael D. Hazel; S. David Smith; Mark E. Wagshul; Fritz Henn; Helene Benveniste; Petar M. Djuric; Grigori Enikolopov; Mirjana Maletic-Savatic
A core aspect of working memory (WM) is the capacity to maintain goal-relevant information in mind, but little is known about how this capacity develops in the human brain. We compared brain activation, via fMRI, between children (ages 7-12 years) and adults (ages 20-29 years) performing tests of verbal and spatial WM with varying amounts (loads)…
Thomason, Moriah E.; Race, Elizabeth; Burrows, Brittany; Whitfield-Gabrieli, Susan; Glover, Gary H.; Gabrieli, John D. E.
A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that,…
ZhuGe, Qichuan; Zhong, Ming; Zheng, WeiMing; Yang, Guo-Yuan; Mao, XiaoOu; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin
Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain. The underlying structural basis of this functional connectivity pattern is still widely unexplored. We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3
Stefan J. Teipel; Arun L. W. Bokde; Thomas Meindl; Edson Amaro; Jasmin Soldner; Maximilian F. Reiser; Sabine C. Herpertz; Hans-Jürgen Möller; Harald Hampel
This volume presents coverage of the use of positron emission tomography (PET) to study the human brain. The contributors assess new developments in high-resolution positron emission tomography, cyclotrons, radiochemistry, and tracer kinetic models, and explore the use of PET in brain energy metabolism, blood flow, and protein synthesis measurements, receptor analysis, and pH determinations, In addition, they discuss the relevance
T. Greitz; D. H. Ingvar; L. Widen
Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3? that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3?), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases.
Pramparo, Tiziano; Libiger, Ondrej; Jain, Sonia; Li, Hong; Youn, Yong Ha; Hirotsune, Shinji; Schork, Nicholas J.; Wynshaw-Boris, Anthony
The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA?31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed. PMID:24788455
Thomason, Moriah E; Brown, Jesse A; Dassanayake, Maya T; Shastri, Rupal; Marusak, Hilary A; Hernandez-Andrade, Edgar; Yeo, Lami; Mody, Swati; Berman, Susan; Hassan, Sonia S; Romero, Roberto
The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA?31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.
Thomason, Moriah E.; Brown, Jesse A.; Dassanayake, Maya T.; Shastri, Rupal; Marusak, Hilary A.; Hernandez-Andrade, Edgar; Yeo, Lami; Mody, Swati; Berman, Susan; Hassan, Sonia S.; Romero, Roberto
Human neural transplants are being developed to treat Par- kinson's disease. Previous characterization of human trans- plants focused on neuronal development, while little is known of the interaction between the transplant and its environ- ment, among which blood is of prime importance. We eval- uated here the formation of blood vessels in human neural xenografts placed into the brain of
Christian Geny; Souad Naimi-Sadaoui; Roland Jeny; Sharon L. Juliano
Differences in cognitive abilities and the relatively large brain are among the most striking differences between humans and their closest primate relatives. The energy trade-off hypothesis predicts that a major shift in energy allocation among tissues occurred during human origins in order to support the remarkable expansion of a metabolically expensive brain. However, the molecular basis of this adaptive scenario is unknown. Two glucose transporters (SLC2A1 and SLC2A4) are promising candidates and present intriguing mutations in humans, resulting, respectively, in microcephaly and disruptions in whole-body glucose homeostasis. We compared SLC2A1 and SLC2A4 expression between humans, chimpanzees and macaques, and found compensatory and biologically significant expression changes on the human lineage within cerebral cortex and skeletal muscle, consistent with mediating an energy trade-off. We also show that these two genes are likely to have undergone adaptation and participated in the development and maintenance of a larger brain in the human lineage by modulating brain and skeletal muscle energy allocation. We found that these two genes show human-specific signatures of positive selection on known regulatory elements within their 5?-untranslated region, suggesting an adaptation of their regulation during human origins. This study represents the first case where adaptive, functional and genetic lines of evidence implicate specific genes in the evolution of human brain size.
Fedrigo, Olivier; Pfefferle, Adam D.; Babbitt, Courtney C.; Haygood, Ralph; Wall, Christine E.; Wray, Gregory A.
DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role,
Vassiliki Fotaki; Mara Dierssen; Soledad Alcantara; S. Martinez; E. Marti; Caty Casas; Joana Visa; Eduardo Soriano; Xavier Estivill; Maria L. Arbones
... human brain. Miller JA, Ding S-L, Sunkin SM, Smith KA, Ng L, Szafer A, Ebbert A, Riley ... Shapovalova NV, Shen EH, Sjoquist N, Slaughterbeck CR, Smith M, Sodt AJ, Williams D, Zöllei L, Fischl ...
The capacity to look inside the living human brain and image its function has been present since the early 1980s. There are some clinicians who use functional brain imaging for diagnostic or prognostic purposes, but much of the work done still relates to research evaluation of brain function. There is a striking dichotomy in the use of functional brain imaging between these two fields. Clinical evaluation of a brain PET or SPECT scan is subjective; that is, a Nuclear Medicine physician examines the brain image, and states whether the brain image looks normal or abnormal. On the other hand, modern research evaluation of functional brain images is almost always objective. Brain images are processed and analyzed with advanced software tools, and a mathematical result that relates to regional changes in brain activity is provided. The potential for this research methodology to provide a more accurate and reliable answer to clinical questions about brain function and pathology are immense, but there are still obstacles to overcome. Foremost in this regard is the use of a standardized normal control database for comparison of patient scan data. The tools and methods used in objective analysis of functional imaging data, as well as potential clinical applications will be the focus of my presentation.
Patterson, James C. II [Louisiana State University Health Science Center, Biomedical Research Foundation of Northwest Louisiana, 1501 Kings Highway, Shreveport, Louisiana, 71103 (United States); PET Imaging Center, Biomedical Research Foundation of Northwest Louisiana, 1501 Kings Highway, Shreveport, Louisiana, 71103 (United States)
When we change our mind about something, does it change our brains? According to George Lakoff, the way we view the world is conditioned by frames, metaphors and narratives that, over time, become hard-wired in our brains. It is not easy to overcome established patterns of thought (or our instincts) when trying to make sense of new information. Is the
David F. Batten
Language is a characteristic feature of human communication. Several familial language impairments have been identified, and candidate genes for language impairments already isolated. Studies comparing expression patterns of these genes in human brain are necessary to further understanding of these genes. However, it is difficult to examine gene expression in human brain. In this study, we used a non-human primate (common marmoset; Callithrix jacchus) as a biological model of the human brain to investigate expression patterns of human speech- and reading-related genes. Expression patterns of speech disorder- (FoxP2, FoxP1, CNTNAP2, and CMIP) and dyslexia- (ROBO1, DCDC2, and KIAA0319) related genes were analyzed. We found the genes displayed overlapping expression patterns in the ocular, auditory, and motor systems. Our results enhance understanding of the molecular mechanisms underlying language impairments. PMID:24769279
Kato, Masaki; Okanoya, Kazuo; Koike, Taku; Sasaki, Erika; Okano, Hideyuki; Watanabe, Shigeru; Iriki, Atsushi
The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair. PMID:23395372
Espuny-Camacho, Ira; Michelsen, Kimmo A; Gall, David; Linaro, Daniele; Hasche, Anja; Bonnefont, Jérôme; Bali, Camilia; Orduz, David; Bilheu, Angéline; Herpoel, Adèle; Lambert, Nelle; Gaspard, Nicolas; Péron, Sophie; Schiffmann, Serge N; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre
Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density. PMID:16025450
Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel
Cytokines may play a pathogenetic role in the brain. Using human fetal brain cell cultures, we investigated whether cytokines released during inflammation modulate neuronal injury. Exposure of human fetal neuronal cells to the excitatory amino acid neurotransmitter, glutamate, for 6 days resulted in a dose-dependent cell loss. Tumor necrosis factor (TNF)-a potentiated glutamate neurotoxicity. This TNF?-potentiated glutamate neurotoxicity was blocked
Chun C. Chao; Shuxian Hu
BACKGROUND: S100B is considered an astrocytic in-situ marker and protein levels in cerebrospinal fluid (CSF) or serum are often used as biomarker for astrocytic damage or dysfunction. However, studies on S100B in the human brain are rare. Thus, the distribution of S100B was studied by immunohistochemistry in adult human brains to evaluate its cell-type specificity. RESULTS: Contrary to glial fibrillary
Johann Steiner; Hans-Gert Bernstein; Hendrik Bielau; Annika Berndt; Ralf Brisch; Christian Mawrin; Gerburg Keilhoff; Bernhard Bogerts
The regional distribution of pro-opiocortin-derived peptides and methionine enkephalin was investigated in human brain post-mortem. Sequence-directed radioimmunoassays for ?-endorphin, ?-lipotropin, adrenocorticotrophin, corticotrophin-like intermediate lobe peptide (ACTH18–39, CLIP) ?-MSH and methionine enkephalin were used and 40 different human brain areas were assayed. The regional distribution of all the pro-opiomelanocortin-derived immunoreactivi-ties were correlated with highest amounts of ?-endorphin, ?-lipotropin and ACTH in
Piers C. Emson; Roger Corder; Sally J. Ratter; Sue Tomlin; Philip J. Lowry; Lesley H. Rees; Alberto Arregui; Martin N. Rossor
Aluminum (Al) is potentially toxic for mammals. In contrast to well documented Al neurotoxicity, neurobehavioral studies of Al in rodents have generally not produced robust or consistent results. In the present study, 16 young male (21 days old) and 16 old male (18 months) rats were exposed to 0 (control group) and 100 mg/kg/day of Al administered as Al nitrate nonahydrate in drinking water concurrently with citric acid (356 mg/kg/day) for a period of 100 days. At the end of the exposure period, rats were evaluated for motor activity in an open-field apparatus and learning in a passive avoidance test. After behavioral testing, rats were sacrificed and brain samples were collected to determine Al concentrations and to study synapses in the left CA1 fields of hippocampal formation. While no significant effects of Al exposure between groups could be detected on behavior, the total number of synapses decreased with age and Al exposure. In turn, the percentage of perforated synapses significantly increased in old Al-loaded rats. PMID:12520767
Colomina, M Teresa; Roig, José L; Sánchez, Domènec J; Domingo, José L