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Sample records for affect normal brain

  1. Normal language in abnormal brains.

    PubMed

    Piattelli-Palmarini, Massimo

    2017-02-27

    There is little doubt that, in the adult, specific brain lesions cause specific language deficits. Yet, brain localizations of linguistic functions are made problematic by several reported cases of normal language in spite of major brain anomalies, mostly, but not exclusively, occurring early in life. The signal cases are hydrocephaly, spina bifida and hemispherectomy. These cases are discussed and possible solutions are suggested: namely a vast redundancy of neurons and/or the role of microtubules as neuron-internal processors and key factors in signaling and guiding the growth and reconfiguration of the brain.

  2. How Body Affects Brain.

    PubMed

    Suzuki, Wendy A

    2016-08-09

    Studies show that physical exercise can affect a range of brain and cognitive functions. However, little is known about the peripheral signals that initiate these central changes. Moon et al. (2016) provide exciting new evidence that a novel myokine, cathepsin B (CTSB), released with exercise is associated with improved memory.

  3. Monoclonal antibody against a peptide of human prion protein discriminates between Creutzfeldt-Jacob's disease-affected and normal brain tissue.

    PubMed

    Curin Serbec, Vladka; Bresjanac, Mara; Popovic, Mara; Pretnar Hartman, Katrina; Galvani, Vesna; Rupreht, Ruth; Cernilec, Maja; Vranac, Tanja; Hafner, Iva; Jerala, Roman

    2004-01-30

    Current methods for diagnosing transmissible spongiform encephalopathies rely on the degradation of the cellular prion protein (PrP(C)) and the subsequent detection of the protease-resistant remnant of the pathological prion isoform PrP(Sc) by antibodies that react with all forms of PrP. We report on a monoclonal antibody, V5B2, raised against a peptide from the C-terminal part of PrP, which recognizes an epitope specific to PrP(Sc). In cryostat sections from Creutzfeldt-Jacob's disease (CJD) patients' brains, V5B2 selectively labels various deposits of PrP(Sc) without any pretreatment for removal of PrP(C). V5B2 does not bind to non-CJD brain samples or to recombinant PrP, either in its native or denatured form. Specificity for PrP is confirmed by a sandwich enzyme-linked immunosorbent assay utilizing V5B2, which discriminates between CJD and normal samples without proteinase K treatment, and by immunoprecipitation from CJD brain homogenate. The PrP(Sc)-specific epitope is disrupted by denaturation. We conclude that the C-terminal part of PrP in disease-associated PrP(Sc) aggregates forms a structural epitope whose conformation is distinct from that of PrP(C).

  4. Normal development of brain circuits.

    PubMed

    Tau, Gregory Z; Peterson, Bradley S

    2010-01-01

    Spanning functions from the simplest reflex arc to complex cognitive processes, neural circuits have diverse functional roles. In the cerebral cortex, functional domains such as visual processing, attention, memory, and cognitive control rely on the development of distinct yet interconnected sets of anatomically distributed cortical and subcortical regions. The developmental organization of these circuits is a remarkably complex process that is influenced by genetic predispositions, environmental events, and neuroplastic responses to experiential demand that modulates connectivity and communication among neurons, within individual brain regions and circuits, and across neural pathways. Recent advances in neuroimaging and computational neurobiology, together with traditional investigational approaches such as histological studies and cellular and molecular biology, have been invaluable in improving our understanding of these developmental processes in humans in both health and illness. To contextualize the developmental origins of a wide array of neuropsychiatric illnesses, this review describes the development and maturation of neural circuits from the first synapse through critical periods of vulnerability and opportunity to the emergent capacity for cognitive and behavioral regulation, and finally the dynamic interplay across levels of circuit organization and developmental epochs.

  5. Flow of affective information between communicating brains.

    PubMed

    Anders, Silke; Heinzle, Jakob; Weiskopf, Nikolaus; Ethofer, Thomas; Haynes, John-Dylan

    2011-01-01

    When people interact, affective information is transmitted between their brains. Modern imaging techniques permit to investigate the dynamics of this brain-to-brain transfer of information. Here, we used information-based functional magnetic resonance imaging (fMRI) to investigate the flow of affective information between the brains of senders and perceivers engaged in ongoing facial communication of affect. We found that the level of neural activity within a distributed network of the perceiver's brain can be successfully predicted from the neural activity in the same network in the sender's brain, depending on the affect that is currently being communicated. Furthermore, there was a temporal succession in the flow of affective information from the sender's brain to the perceiver's brain, with information in the perceiver's brain being significantly delayed relative to information in the sender's brain. This delay decreased over time, possibly reflecting some 'tuning in' of the perceiver with the sender. Our data support current theories of intersubjectivity by providing direct evidence that during ongoing facial communication a 'shared space' of affect is successively built up between senders and perceivers of affective facial signals.

  6. CT scanning phantom for normalization of infant brain attenuation.

    PubMed

    Thompson, J R; Triolo, P J; Moore, R J; Hinshaw, D B; Hasso, A N

    1984-01-01

    The x-ray attenuation values of brain studied with computed tomography (CT) are strikingly affected by the ages of the subjects. Premature neonates, for example, may have brain attenuation values 20-30 H below adult values. These lower attenuation values for developing compared with adult brain can be ascribed partly to machine-related effects (beam-hardening, adult algorithms, scanning geometry, etc.). A scanning phantom made from aluminum was developed that can be used to develop a nomogram for any particular scanner from which normalized brain attenuation may be derived for any small head size. Using this nomogram, predicted neonatal attenuations are still 10-15 H higher than those actually observed in scanning neonates. The model predicts that, at the most, 3-4 H of this discrepancy can be accounted for by less beam-hardening from the lower bone attenuation of the thinner developing skull. Presumably, the rest is from a lower brain density in neonates (higher water content). By normalizing to cerebrospinal fluid (water) with special care to avoid partial-volume artifacts, one can predict attenuation values for developing brain more accurately.

  7. A quantitative transcriptome reference map of the normal human brain.

    PubMed

    Caracausi, Maria; Vitale, Lorenza; Pelleri, Maria Chiara; Piovesan, Allison; Bruno, Samantha; Strippoli, Pierluigi

    2014-10-01

    We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by 'real-time' reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.

  8. Brain cholinesterase activity of apparently normal wild birds

    USGS Publications Warehouse

    Hill, E.F.

    1988-01-01

    Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%.

  9. Ultrasound, normal fetus- ventricles of brain (image)

    MedlinePlus

    Images ... of brain ventricles. Ventricles are spaces in the brain that are filled with fluid. In this early ultrasound, the ventricles can be seen as light lines extending through the skull, seen in the upper right side of the image.

  10. Nutrients affecting brain composition and behavior

    NASA Technical Reports Server (NTRS)

    Wurtman, R. J.

    1987-01-01

    This review examines the changes in brain composition and in various brain functions, including behavior, that can follow the ingestion of particular foods or nutrients. It details those that are best understood: the increases in serotonin, catecholamine, or acetylcholine synthesis that can occur subsequent to food-induced increases in brain levels of tryptophan, tyrosine, or choline; it also discusses the various processes that must intervene between the mouth and the synapse, so to speak, in order for a nutrient to affect neurotransmission, and it speculates as to additional brain chemicals that may ultimately be found to be affected by changes in the availability of their nutrient precursors. Because the brain chemicals best known to be nutrient dependent overlap with those thought to underlie the actions of most of the drugs used to treat psychiatric diseases, knowledge of this dependence may help the psychiatrist to understand some of the pathologic processes occurring in his/her patients, particularly those with appetitive symptoms. At the very least, such knowledge should provide the psychiatrist with objective criteria for judging when to take seriously assertions that particular foods or nutrients do indeed affect behavior (e.g., in hyperactive children). If the food can be shown to alter neurotransmitter release, it may be behaviorally-active; however, if it lacks a discernible neurochemical effect, the likelihood that it really alters behavior is small.

  11. Adolescent brain development in normality and psychopathology

    PubMed Central

    LUCIANA, MONICA

    2014-01-01

    Since this journal’s inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical–cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology–context interactions, represent the field’s most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled. PMID:24342843

  12. Adolescent brain development in normality and psychopathology.

    PubMed

    Luciana, Monica

    2013-11-01

    Since this journal's inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical-cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology-context interactions, represent the field's most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled.

  13. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

  14. The autistic brain in the context of normal neurodevelopment

    PubMed Central

    Ziats, Mark N.; Edmonson, Catherine; Rennert, Owen M.

    2015-01-01

    The etiology of autism spectrum disorders (ASDs) is complex and largely unclear. Among various lines of inquiry, many have suggested convergence onto disruptions in both neural circuitry and immune regulation/glial cell function pathways. However, the interpretation of the relationship between these two putative mechanisms has largely focused on the role of exogenous factors and insults, such as maternal infection, in activating immune pathways that in turn result in neural network abnormalities. Yet, given recent insights into our understanding of human neurodevelopment, and in particular the critical role of glia and the immune system in normal brain development, it is important to consider these putative pathological processes in their appropriate normal neurodevelopmental context. In this review, we explore the hypothesis that the autistic brain cellular phenotype likely represents intrinsic abnormalities of glial/immune processes constitutively operant in normal brain development that result in the observed neural network dysfunction. We review recent studies demonstrating the intercalated role of neural circuit development, the immune system, and glial cells in the normal developing brain, and integrate them with studies demonstrating pathological alterations in these processes in autism. By discussing known abnormalities in the autistic brain in the context of normal brain development, we explore the hypothesis that the glial/immune component of ASD may instead be related to intrinsic exaggerated/abnormal constitutive neurodevelopmental processes such as network pruning. Moreover, this hypothesis may be relevant to other neurodevelopmental disorders that share genetic, pathologic, and clinical features with autism. PMID:26379512

  15. Affective brain-computer music interfacing

    NASA Astrophysics Data System (ADS)

    Daly, Ian; Williams, Duncan; Kirke, Alexis; Weaver, James; Malik, Asad; Hwang, Faustina; Miranda, Eduardo; Nasuto, Slawomir J.

    2016-08-01

    Objective. We aim to develop and evaluate an affective brain-computer music interface (aBCMI) for modulating the affective states of its users. Approach. An aBCMI is constructed to detect a user's current affective state and attempt to modulate it in order to achieve specific objectives (for example, making the user calmer or happier) by playing music which is generated according to a specific affective target by an algorithmic music composition system and a case-based reasoning system. The system is trained and tested in a longitudinal study on a population of eight healthy participants, with each participant returning for multiple sessions. Main results. The final online aBCMI is able to detect its users current affective states with classification accuracies of up to 65% (3 class, p\\lt 0.01) and modulate its user's affective states significantly above chance level (p\\lt 0.05). Significance. Our system represents one of the first demonstrations of an online aBCMI that is able to accurately detect and respond to user's affective states. Possible applications include use in music therapy and entertainment.

  16. Diagnosing pseudobulbar affect in traumatic brain injury

    PubMed Central

    Engelman, William; Hammond, Flora M; Malec, James F

    2014-01-01

    Pseudobulbar affect (PBA) is defined by episodes of involuntary crying and/or laughing as a result of brain injury or other neurological disease. Epidemiology studies show that 5.3%–48.2% of people with traumatic brain injury (TBI) may have symptoms consistent with (or suggestive of) PBA. Yet it is a difficult and often overlooked condition in individuals with TBI, and is easily confused with depression or other mood disorders. As a result, it may be undertreated and persist for longer than it should. This review presents the signs and symptoms of PBA in patients with existing TBI and outlines how to distinguish PBA from other similar conditions. It also compares and contrasts the different diagnostic criteria found in the literature and briefly mentions appropriate treatments. This review follows a composite case with respect to the clinical course and treatment for PBA and presents typical challenges posed to a provider when diagnosing PBA. PMID:25336956

  17. [Neuroethics (I): moral pathways in normal brain].

    PubMed

    Álvaro-González, Luis C

    2014-03-01

    Introduccion. La moralidad es el conjunto de normas y valores que guian la conducta. Se mantienen en muy diferentes culturas. Permiten alcanzar logros sociales que solo se entienden bajo el desarrollo moral, con un sentido de justicia que penetra toda accion humana. Las funciones morales, fruto del desarrollo evolutivo, asientan en circuitos neuronales propios. Objetivo. Describir su aparicion, puesta en marcha y mecanismos operativos en el cerebro normal. Desarrollo. Las respuestas morales, en lo esencial homogeneas, estan muy vinculadas al desarrollo emocional, tanto basico e individual (miedo o ira) como social (compasion o justicia). Aparecen a partir de los binomios emocionales placer/dolor y recompensa/castigo, que conducen al binomio moral basico bueno/malo. En su puesta en marcha intervienen la corteza prefrontal (ventromedial y dorsolateral), la corteza cingular anterior y el sulco temporal superior, que serian evaluativos y elaborativos, utilitaristas; tambien la insula, la amigdala y el hipotalamo, ejecutivos de las respuestas morales mas emocionales puras y rapidas. Asimismo, es importante el sistema de neuronas espejo (frontoparietal), que permite el aprendizaje motor y las conductas empaticas, con las que se vincula con la teoria de la mente. Conclusiones. El desarrollo del sentido moral y sus respuestas nos han permitido alcanzar una complejidad y convivencia social que redundan en beneficio de la especie e individuos. El conocimiento del funcionamiento moral esta influyendo tambien en territorios diversos de la neurocultura.

  18. Positron brain imaging--normal patterns and asymmetries

    SciTech Connect

    Finklestein, S.; Alpert, N.M.; Ackerman, R.H.; Correia, J.A.; Buonanno, F.S.; Chang, J.; Brownell, G.L.; Taveras, J.M.

    1982-07-01

    Regional brain physiology was investigated in 11 normal resting right-handed subjects using positron emission tomography. Cerebral blood flow was studied in all subjects. Cerebral oxygen metabolism was studied in six subjects, and cerebral glucose metabolism was also studied in one subject. In five subjects, physiological activity was higher in left frontotemporal regions than right. These findings may be related to structural cerebral asymmetries or to activation of brain language centers.

  19. Effects of photoradiation therapy on normal rat brain

    SciTech Connect

    Cheng, M.K.; McKean, J.; Boisvert, D.; Tulip, J.; Mielke, B.W.

    1984-12-01

    Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. The authors conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

  20. Normalization of brain morphology after surgery in sagittal craniosynostosis.

    PubMed

    Brooks, Eric D; Yang, Jenny; Beckett, Joel S; Lacadie, Cheryl; Scheinost, Dustin; Persing, Sarah; Zellner, Elizabeth G; Oosting, Devon; Keifer, Cara; Friedman, Hannah E; Wyk, Brent Vander; Jou, Roger J; Sun, Haosi; Gary, Cyril; Duncan, Charles C; Constable, R Todd; Pelphrey, Kevin A; Persing, John A

    2016-04-01

    OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 × 1.05 × 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty

  1. Transcranial magnetic stimulation of degenerating brain: a comparison of normal aging, Alzheimer's, Parkinson's and Huntington's disease.

    PubMed

    Ljubisavljevic, M R; Ismail, F Y; Filipovic, S

    2013-07-01

    Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.

  2. Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function.

    PubMed

    Braun, S M G; Jessberger, S

    2014-02-01

    Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to generate new neurones throughout life in discrete brain regions, through a process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult brain circuitry plasticity, has been implicated in physiological brain function and appears to be of pivotal importance for certain forms of learning and memory. In addition, failing or altered neurogenesis has been associated with a variety of brain diseases such as major depression, epilepsy and age-related cognitive decline. Here we review recent advances in our understanding of the basic biology underlying the neurogenic process in the adult brain, focusing on mechanisms that regulate quiescence, proliferation and differentiation of NSPCs. In addition, we discuss how neurogenesis influences normal brain function, and in particular its role in memory formation, as well as its contribution to neuropsychiatric diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for brain repair.

  3. Normal feline brain: clinical anatomy using magnetic resonance imaging.

    PubMed

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

    2012-04-01

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

  4. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

    PubMed

    Bauer, M; London, E D; Silverman, D H; Rasgon, N; Kirchheiner, J; Whybrow, P C

    2003-11-01

    The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

  5. Seizures and antiepileptic drugs: does exposure alter normal brain development?

    PubMed

    Marsh, Eric D; Brooks-Kayal, Amy R; Porter, Brenda E

    2006-12-01

    Seizures and antiepileptic drugs (AEDs) affect brain development and have long-term neurological consequences. The specific molecular and cellular changes, the precise timing of their influence during brain development, and the full extent of the long-term consequences of seizures and AEDs exposure have not been established. This review critically assesses both the basic and clinical science literature on the effects of seizures and AEDs on the developing brain and finds that evidence exists to support the hypothesis that both seizures and antiepileptic drugs influence a variety of biological process, at specific times during development, which alter long-term cognition and epilepsy susceptibility. More research, both clinical and experimental, is needed before changes in current clinical practice, based on the scientific data, can be recommended.

  6. The endocannabinoid system in normal and pathological brain ageing.

    PubMed

    Bilkei-Gorzo, Andras

    2012-12-05

    The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

  7. Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

    ERIC Educational Resources Information Center

    Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

    2008-01-01

    Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

  8. Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.

    EPA Science Inventory

    At some level, carboxyhemoglobin (RbCO) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in normal and ischemic heart patients. At high RbCO levels in normal subjects, brain function is also affected and behavioral performance is impaired. These are fin...

  9. Characterization of integrin receptors in normal and neoplastic human brain.

    PubMed Central

    Paulus, W.; Baur, I.; Schuppan, D.; Roggendorf, W.

    1993-01-01

    We studied the immunohistochemical expression of integrin alpha and beta chains in the normal and neoplastic human brain. Normal astrocytes expressed alpha 2, alpha 3, alpha 6, beta 1, and beta 4 chains in some areas facing major interstitial tissues, but they were consistently negative for the other integrins examined (alpha 4, alpha 5, alpha V, alpha L, alpha M, alpha X, beta 2, beta 3). Neoplastic astrocytes in vivo and in vitro showed increased expression of alpha 3 and beta 1, and some also of alpha 5, alpha V, beta 3, and beta 4. Neoexpression of alpha 4 and reduced levels of beta 4 were detected in glioblastoma vascular proliferations compared with normal endothelial cells. Oligodendroglioma, ependymoma, choroid plexus papilloma, pituitary adenoma, and meningioma cells showed the same integrin pattern as their normal counterparts. Adhesion assays using the astrocytoma cell lines U-138 MG and U-373 MG revealed strong attachment to collagen types I to VI and undulin, which was inhibited by antibodies to beta 1, but not by those to alpha 2, alpha 3, alpha 6, and alpha V. We conclude that astrocytomas show increased levels or neoexpression of various integrins and strong attachment to various extracellular matrix components, which appears to be almost exclusively mediated by beta 1-integrins. Images Figure 1 PMID:8317546

  10. ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide.

    PubMed

    Thompson, Paul M; Andreassen, Ole A; Arias-Vasquez, Alejandro; Bearden, Carrie E; Boedhoe, Premika S; Brouwer, Rachel M; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cannon, Dara M; Cohen, Ronald A; Conrod, Patricia J; Dale, Anders M; Deary, Ian J; Dennis, Emily L; de Reus, Marcel A; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C; Grabe, Hans J; Guadalupe, Tulio; Gutman, Boris A; Hashimoto, Ryota; Hibar, Derrek P; Holland, Dominic; Hoogman, Martine; Pol, Hilleke E Hulshoff; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S; Lee, Phil H; Mackey, Scott; Martin, Nicholas G; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E; Morey, Rajendra A; Nichols, Thomas E; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M; Smit, Dirk J A; Smoller, Jordan W; Stein, Dan J; Stein, Jason L; Toro, Roberto; Turner, Jessica A; van den Heuvel, Martijn P; van den Heuvel, Odile L; van Erp, Theo G M; van Rooij, Daan; Veltman, Dick J; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M; Whelan, Christopher D; Wright, Margaret J; Ye, Jieping

    2017-01-15

    In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

  11. Presence of corticotropin in brain of normal and hypophysectomized rats.

    PubMed Central

    Krieger, D T; Liotta, A; Brownstein, M J

    1977-01-01

    Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH. Images PMID:191820

  12. Normal brain volume measurements using multispectral MRI segmentation.

    PubMed

    Vaidyanathan, M; Clarke, L P; Heidtman, C; Velthuizen, R P; Hall, L O

    1997-01-01

    The performance of a supervised k-nearest neighbor (kNN) classifier and a semisupervised fuzzy c-means (SFCM) clustering segmentation method are evaluated for reproducible measurement of the volumes of normal brain tissues and cerebrospinal fluid. The stability of the two segmentation methods is evaluated for (a) operator selection of training data, (b) reproducibility during repeat imaging sessions to determine any variations in the sensor performance over time, (c) variations in the measured volumes between different subjects, and (d) variability with different imaging parameters. The variations were found to be dependent on the type of measured tissue and the operator performing the segmentations. The variability during repeat imaging sessions for the SFCM method was < 3%. The absolute volumes of the brain matter and cerebrospinal fluid between subjects varied quite large, ranging from 9% to 13%. The intraobserver and interobserver reproducibility for SFCM were < 4% for the soft tissues and 6% for cerebrospinal fluid. The corresponding results for the kNN segmentation method were higher compared to the SFCM method.

  13. Long-term influence of normal variation in neonatal characteristics on human brain development

    PubMed Central

    Walhovd, Kristine B.; Fjell, Anders M.; Brown, Timothy T.; Kuperman, Joshua M.; Chung, Yoonho; Hagler, Donald J.; Roddey, J. Cooper; Erhart, Matthew; McCabe, Connor; Akshoomoff, Natacha; Amaral, David G.; Bloss, Cinnamon S.; Libiger, Ondrej; Schork, Nicholas J.; Darst, Burcu F.; Casey, B. J.; Chang, Linda; Ernst, Thomas M.; Frazier, Jean; Gruen, Jeffrey R.; Kaufmann, Walter E.; Murray, Sarah S.; van Zijl, Peter; Mostofsky, Stewart; Dale, Anders M.; Jernigan, Terry L.; McCabe, Connor; Chang, Linda; Akshoomoff, Natacha; Newman, Erik; Dale, Anders M.; Ernst, Thomas; Dale, Anders M.; Van Zijl, Peter; Kuperman, Joshua; Murray, Sarah; Bloss, Cinnamon; Schork, Nicholas J.; Appelbaum, Mark; Gamst, Anthony; Thompson, Wesley; Bartsch, Hauke; Jernigan, Terry L.; Dale, Anders M.; Akshoomoff, Natacha; Chang, Linda; Ernst, Thomas; Keating, Brian; Amaral, David; Sowell, Elizabeth; Kaufmann, Walter; Van Zijl, Peter; Mostofsky, Stewart; Casey, B.J.; Ruberry, Erika J.; Powers, Alisa; Rosen, Bruce; Kenet, Tal; Frazier, Jean; Kennedy, David; Gruen, Jeffrey

    2012-01-01

    It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences. PMID:23169628

  14. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

  15. The impact of normalization and segmentation on resting-state brain networks.

    PubMed

    Magalhães, Ricardo; Marques, Paulo; Soares, José; Alves, Victor; Sousa, Nuno

    2015-04-01

    Graph theory has recently received a lot of attention from the neuroscience community as a method to represent and characterize brain networks. Still, there is a lack of a gold standard for the methods that should be employed for the preprocessing of the data and the construction of the networks, as well as a lack of knowledge on how different methodologies can affect the metrics reported. The authors used graph theory analysis applied to resting-state functional magnetic resonance imaging to investigate the influence of different node-defining strategies and the effect of normalizing the functional acquisition on several commonly reported metrics used to characterize brain networks. The nodes of the network were defined using either the individual FreeSurfer segmentation of each subject or the FreeSurfer segmented Montreal National Institute (MNI) 152 template, using the Destrieux and subcortical atlas. The functional acquisition was either kept on the functional native space or normalized into MNI standard space. The comparisons were done at three levels: on the connections, on the edge properties, and on the network properties levels. The results reveal that different registration and brain parcellation strategies have a strong impact on all the levels of analysis, possibly favoring the use of individual segmentation strategies and conservative registration approaches. In conclusion, several technical aspects must be considered so that graph theoretical analysis of connectivity MRI data can provide a framework to understand brain pathologies.

  16. Association of structural global brain network properties with intelligence in normal aging.

    PubMed

    Fischer, Florian U; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2014-01-01

    Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  17. Brain response to affective pictures in the chimpanzee.

    PubMed

    Hirata, Satoshi; Matsuda, Goh; Ueno, Ari; Fukushima, Hirokata; Fuwa, Koki; Sugama, Keiko; Kusunoki, Kiyo; Tomonaga, Masaki; Hiraki, Kazuo; Hasegawa, Toshikazu

    2013-01-01

    Advancement of non-invasive brain imaging techniques has allowed us to examine details of neural activities involved in affective processing in humans; however, no comparative data are available for chimpanzees, the closest living relatives of humans. In the present study, we measured event-related brain potentials in a fully awake adult chimpanzee as she looked at affective and neutral pictures. The results revealed a differential brain potential appearing 210 ms after presentation of an affective picture, a pattern similar to that in humans. This suggests that at least a part of the affective process is similar between humans and chimpanzees. The results have implications for the evolutionary foundations of emotional phenomena, such as emotional contagion and empathy.

  18. A preliminary comparison of flat affect schizophrenics and brain-damaged patients on measures of affective processing.

    PubMed

    Borod, J C; Alpert, M; Brozgold, A; Martin, C; Welkowitz, J; Diller, L; Peselow, E; Angrist, B; Lieberman, A

    1989-04-01

    Flat affect is a major component of schizophrenia and is often also seen in neurological disorders. A preliminary set of comparisons were conducted to delineate neuropsychological mechanisms underlying flat affect in schizophrenia, and new measures are described for the assessment of affective deficits in clinical populations. Subjects were schizophrenic with flat affect (SZs), right brain-damaged (RBD), Parkinson's Disease (PDs), and normal control (NC) right-handed adults. Subjects were administered affective measures of expression and perception in both facial and vocal channels. For both perceptual and expressive tasks the SZs performed significantly less accurately than the NCs and the PDs but did not differ from the RBDs. This was the case for both face and voice. This finding lends support to the speculation that right hemisphere mechanisms, especially cortical ones, may be compromised among schizophrenics with flat affect.

  19. Cranial index of children with normal and abnormal brain development in Sokoto, Nigeria: A comparative study

    PubMed Central

    Musa, Muhammad Awwal; Zagga, Abdullahi Daudu; Danfulani, Mohammed; Tadros, Aziz Abdo; Ahmed, Hamid

    2014-01-01

    Background: Abnormal brain development due to neurodevelopmental disorders in children has always been an important concern, but yet has to be considered as a significant public health problem, especially in the low- and middle-income countries including Nigeria. Aims: The aim of this study is to determine whether abnormal brain development in the form of neurodevelopmental disorders causes any deviation in the cranial index of affected children. Materials and Methods: This is a comparative study on the head length, head width, and cranial index of 112 children (72 males and 40 females) diagnosed with at least one abnormal problem in brain development, in the form of a neurodevelopmental disorder (NDD), in comparison with that of 218 normal growing children without any form of NDD (121 males and 97 females), aged 0-18 years old seen at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, over a period of six months, June to December, 2012. The head length and head width of the children was measured using standard anatomical landmarks and cranial index calculated. The data obtained was entered into the Microsoft excel worksheet and analyzed using SPSS version 17. Results: The mean Cephalic Index for normal growing children with normal brain development was 79.82 ± 3.35 and that of the children with abnormal brain development was 77.78 ± 2.95 and the difference between the two groups was not statistically significant (P > 0.05). Conclusion: It can be deduced from this present study that the cranial index does not change in children with neurodevelopmental disorders. PMID:24966551

  20. Biochemical and histochemical comparison of cholinesterases in normal and Alzheimer brain tissues.

    PubMed

    Darvesh, S; Reid, G A; Martin, E

    2010-08-01

    Cholinesterase activity associated with neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains exhibit altered histochemical properties, such as requiring lower pH (6.8) for optimal cholinesterase staining compared to the pH (8.0) for best visualization of cholinesterases in neurons. Furthermore, visualization of NPs and NFTs can be prevented by agents like the peptidase inhibitor/metalloantibiotic bacitracin. The anomalous behavior of cholinesterases associated with pathological lesions needs to be elucidated because of the putative links between these enzymes and the disease process in AD. In this study, cholinesterases were extracted from AD and normal brain tissue to determine whether the differences observed in histochemical analyses in the two sources were reflected in kinetic properties measured in solubilized enzymes. Isolated brain enzymes from both these sources exhibited comparable kinetic parameters with respect to pH dependence, substrate affinity and inhibitor sensitivity and were not significantly affected by other agents that blocked cholinesterase histochemical visualization, such as the structurally diverse metal-chelating antibiotics bacitracin, doxycycline, minocycline and rifampicin. Although the cholinesterases from AD brain tissue examined here represented a total pool of these enzymes from AD brain, rather than enzymes specifically from NPs and NFTs, their kinetic behavior being comparable to cholinesterases isolated from normal brain tissues implies that these enzymes do not undergo disease-related modification in their primary structures. This suggests that the atypical histochemical behavior of cholinesterases in NPs and NFTs may result from interaction of cholinesterases with other molecules within these lesions, mediated by transition metal ions known to be present in AD pathology lesions.

  1. [The child's brain: normal (unaltered) development and development altered by perinatal injury].

    PubMed

    Marín-Padilla, Miguel

    2013-09-06

    In this study we analyse some of the morphological and functional aspects of normal and altered development (the latter due to perinatal injury) in the child's brain. Both normal and altered development are developmental processes that progressively interconnect the different regions. The neuropathological development of subpial and periventricular haemorrhages, as well as that of white matter infarct, are analysed in detail. Any kind of brain damage causes a local lesion with possible remote repercussions. All the components (neurons, fibres, blood capillaries and neuroglias) of the affected region undergo alterations. Those that are destroyed are eliminated by the inflammatory process and those that survive are transformed. The pyramidal neurons with amputated apical dendrites are transformed and become stellate cells, the axonal terminals and those of the radial glial cells are regenerated and the region involved is reinnervated and revascularised with an altered morphology and function (altered local corticogenesis). The specific microvascular system of the grey matter protects its neurons from infarction of the white matter. Although it survives, the grey matter is left disconnected from the afferent and efferent fibres, amputated by the infarct with alterations affecting its morphology and possibly its functioning (altered local corticogenesis). Any local lesion can modify the morphological and functional development of remote regions that are functionally interconnected with it (altered remote corticogenesis). We suggest that any local brain injury can alter the morphology and functioning of the regions that are morphologically and functionally interconnected with it and thus end up affecting the child's neurological and psychological development. These changes can cross different regions of the brain (epileptic auras) and, if they eventually reach the motor region, will give rise to the motor storm that characterises epilepsy.

  2. Thermoregulatory Instability in Childhood: Linking the Normal Brain to Hypothalamic Storm

    PubMed Central

    Fussiger, Helena; Maria Vedana, Viviane; Hemb, Marta

    2016-01-01

    Central core temperature is tightly controlled by hypothalamic centers, a feature that makes sudden changes in body temperature very unusual. A dysfunction of these hypothalamic pathways leads to Shapiro's syndrome, comprising spontaneous hypothermia, hyperhidrosis, and corpus callosum dysgenesis. Although it may affect any age, usually it presents in childhood. Variants to this syndrome with completely normal brain anatomy have been consistently reported, expanding the clinical spectrum of the syndrome. Herein, we report the case of a 4-year-old girl with Shapiro's syndrome and unaffected corpus callosum. PMID:27847661

  3. Alix is required during development for normal growth of the mouse brain

    PubMed Central

    Laporte, Marine H.; Chatellard, Christine; Vauchez, Victoria; Hemming, Fiona J.; Deloulme, Jean-Christophe; Vossier, Frédérique; Blot, Béatrice; Fraboulet, Sandrine; Sadoul, Rémy

    2017-01-01

    Alix (ALG-2 interacting protein X) drives deformation and fission of endosomal and cell surface membranes and thereby intervenes in diverse biological processes including cell proliferation and apoptosis. Using embryonic fibroblasts of Alix knock-out mice, we recently demonstrated that Alix is required for clathrin-independent endocytosis. Here we show that mice lacking Alix suffer from severe reduction in the volume of the brain which affects equally all regions examined. The cerebral cortex of adult animals shows normal layering but is reduced in both medio-lateral length and thickness. Alix controls brain size by regulating its expansion during two distinct developmental stages. Indeed, embryonic surface expansion of the Alix ko cortex is reduced because of the loss of neural progenitors during a transient phase of apoptosis occurring between E11.5 and E12.5. Subsequent development of the Alix ko cortex occurs normally until birth, when Alix is again required for the post-natal radial expansion of the cortex through its capacity to allow proper neurite outgrowth. The need of Alix for both survival of neural progenitor cells and neurite outgrowth is correlated with its role in clathrin-independent endocytosis in neural progenitors and at growth cones. Thus Alix-dependent, clathrin independent endocytosis is essential for controlling brain size. PMID:28322231

  4. Affective state and community integration after traumatic brain injury.

    PubMed

    Juengst, Shannon B; Arenth, Patricia M; Raina, Ketki D; McCue, Michael; Skidmore, Elizabeth R

    2014-12-01

    Previous studies investigating the relationship between affective state and community integration have focused primarily on the influence of depression and anxiety. In addition, they have focused on frequency of participation in various activities, failing to address an individual's subjective satisfaction with participation. The purpose of this study was to examine how affective state contributes to frequency of participation and satisfaction with participation after traumatic brain injury among participants with and without a current major depressive episode. Sixty-four community-dwelling participants with a history of complicated mild-to-severe traumatic brain injury participated in this cross-sectional cohort study. High positive affect contributed significantly to frequency of participation (β = 0.401, P = 0.001), and both high positive affect and low negative affect significantly contributed to better satisfaction with participation (F2,61 = 13.63, P < 0.001). Further investigation to assess the direction of these relationships may better inform effective targets for intervention. These findings highlight the importance of assessing affective state after traumatic brain injury and incorporating a subjective measure of participation when considering community integration outcomes.

  5. Neuroscience of affect: brain mechanisms of pleasure and displeasure.

    PubMed

    Berridge, Kent C; Kringelbach, Morten L

    2013-06-01

    Affective neuroscience aims to understand how affect (pleasure or displeasure) is created by brains. Progress is aided by recognizing that affect has both objective and subjective features. Those dual aspects reflect that affective reactions are generated by neural mechanisms, selected in evolution based on their real (objective) consequences for genetic fitness. We review evidence for neural representation of pleasure in the brain (gained largely from neuroimaging studies), and evidence for the causal generation of pleasure (gained largely from brain manipulation studies). We suggest that representation and causation may actually reflect somewhat separable neuropsychological functions. Representation reaches an apex in limbic regions of prefrontal cortex, especially orbitofrontal cortex, influencing decisions and affective regulation. Causation of core pleasure or 'liking' reactions is much more subcortically weighted, and sometimes surprisingly localized. Pleasure 'liking' is especially generated by restricted hedonic hotspot circuits in nucleus accumbens (NAc) and ventral pallidum. Another example of localized valence generation, beyond hedonic hotspots, is an affective keyboard mechanism in NAc for releasing intense motivations such as either positively valenced desire and/or negatively valenced dread.

  6. Novel Neuroimaging Methods to Understand How HIV Affects the Brain

    PubMed Central

    Thompson, Paul

    2015-01-01

    In much of the developed world, the HIV epidemic has largely been controlled by anti-retroviral treatment. Even so, there is growing concern that HIV-infected individuals may be at risk for accelerated brain aging, and a range of cognitive impairments. What promotes or resists these changes is largely unknown. There is also interest in discovering factors that promote resilience to HIV, and combat its adverse effects in children. Here we review recent developments in brain imaging that reveal how the virus affects the brain. We relate these brain changes to changes in blood markers, cognitive function, and other patient outcomes or symptoms, such as apathy or neuropathic pain. We focus on new and emerging techniques, including new variants of brain MRI. Diffusion tensor imaging, for example, can map the brain’s structural connections while fMRI can uncover functional connections. Finally, we suggest how large-scale global research alliances, such as ENIGMA, may resolve controversies over effects where evidence is now lacking. These efforts pool scans from tens of thousands of individuals, and offer a source of power not previously imaginable for brain imaging studies. PMID:25902966

  7. Photodynamic-therapy-induced alterations of the blood-brain barrier transfer constant of a tracer molecule in normal brain

    NASA Astrophysics Data System (ADS)

    Yeung, Ivan; Lilge, Lothar D.; Wilson, Brian C.; Lee, Ting-Yim; Stevens, Laura; Cenic, Aleksa

    1997-05-01

    Photofrin uptake studies in brain tissues using bulk sampling techniques have demonstrated up to a 10-fold higher concentration in intracranial tumors compared to normal brain structures. This selective uptake is in part attributed to the leaky blood-brain barrier (BBB) in brain tumors while intact BBB in normal brain excludes Photofrin from the extravascular space. However, in vivo preclinical studies have shown a very high sensitivity in normal brain to photodynamic therapy (PDT) despite this selective uptake. In vivo computed tomography (CT) measurement of the blood- brain transfer constant (K) and cerebral plasma volume using an x-ray dye as a tracer was used to monitor the degradation process of the BBB in normal brain during and post PDT. In these experiments, it was observed that K increased as early as 15 minutes after the onset of PDT, peaking at approximately 3 hr post PDT treatment followed by a drop close to baseline values for 3 out of 4 animals. On the other hand, the cerebral plasma volume showed a decrease also as early as 15 min post PDT onset, but its decrease continued up to 6 hrs with no apparent vascular stasis at the end of the time period. The results suggested a continuous process of BBB breakdown and vascular shutdown shortly after start of PDT.

  8. Factors affecting intellectual outcome in pediatric brain tumor patients

    SciTech Connect

    Ellenberg, L.; McComb, J.G.; Siegel, S.E.; Stowe, S.

    1987-11-01

    A prospective study utilizing repeated intellectual testing was undertaken in 73 children with brain tumors consecutively admitted to Childrens Hospital of Los Angeles over a 3-year period to determine the effect of tumor location, extent of surgical resection, hydrocephalus, age of the child, radiation therapy, and chemotherapy on cognitive outcome. Forty-three patients were followed for at least two sequential intellectual assessments and provide the data for this study. Children with hemispheric tumors had the most general cognitive impairment. The degree of tumor resection, adequately treated hydrocephalus, and chemotherapy had no bearing on intellectual outcome. Age of the child affected outcome mainly as it related to radiation. Whole brain radiation therapy was associated with cognitive decline. This was especially true in children below 7 years of age, who experienced a very significant loss of function after whole brain radiation therapy.

  9. The effect of regadenoson-induced transient disruption of the blood-brain barrier on temozolomide delivery to normal rat brain.

    PubMed

    Jackson, Sadhana; Anders, Nicole M; Mangraviti, Antonella; Wanjiku, Teresia M; Sankey, Eric W; Liu, Ann; Brem, Henry; Tyler, Betty; Rudek, Michelle A; Grossman, Stuart A

    2016-02-01

    The blood-brain barrier (BBB) significantly reduces the delivery of many systemically administered agents to the central nervous system. Although temozolomide is the only chemotherapy to improve survival in patients with glioblastoma, its concentration in brain is only 20 % of that in blood. Regadenoson, an FDA approved adenosine receptor agonist used for cardiac stress testing, transiently disrupts rodent BBB allowing high molecular weight dextran (70 kD) to enter the brain. This study was conducted to determine if regadenoson could facilitate entry of temozolomide into normal rodent brain. Temozolomide (50 mg/kg) was administered by oral gavage to non-tumor bearing F344 rats. Two-thirds of the animals received a single dose of intravenous regadenoson 60-90 min later. All animals were sacrificed 120 or 360 min after temozolomide administration. Brain and plasma temozolomide concentrations were determined using HPLC/MS/MS. Brain temozolomide concentrations were significantly higher at 120 min when it was given with regadenoson versus alone (8.1 ± 2.7 and 5.1 ± 3.5 µg/g, P < 0.05). A similar trend was noted in brain:plasma ratios (0.45 ± 0.08 and 0.29 ± 0.09, P < 0.05). Brain concentrations and brain:plasma ratios were not significantly different 360 min after temozolomide administration. No differences were seen in plasma temozolomide concentrations with or without regadenoson. These results suggest co-administration of regadenoson with temozolomide results in 60% higher temozolomide levels in normal brain without affecting plasma concentrations. This novel approach to increasing intracranial concentrations of systemically administered agents has potential to improve the efficacy of chemotherapy in neuro-oncologic disorders.

  10. Factors affecting the cerebral network in brain tumor patients.

    PubMed

    Heimans, Jan J; Reijneveld, Jaap C

    2012-06-01

    Brain functions, including cognitive functions, are frequently disturbed in brain tumor patients. These disturbances may result from the tumor itself, but also from the treatment directed against the tumor. Surgery, radiotherapy and chemotherapy all may affect cerebral functioning, both in a positive as well as in a negative way. Apart from the anti-tumor treatment, glioma patients often receive glucocorticoids and anti-epileptic drugs, which both also have influence on brain functioning. The effect of a brain tumor on cerebral functioning is often more global than should be expected on the basis of the local character of the disease, and this is thought to be a consequence of disturbance of the cerebral network as a whole. Any network, whether it be a neural, a social or an electronic network, can be described in parameters assessing the topological characteristics of that particular network. Repeated assessment of neural network characteristics in brain tumor patients during their disease course enables study of the dynamics of neural networks and provides more insight into the plasticity of the diseased brain. Functional MRI, electroencephalography and especially magnetoencephalography are used to measure brain function and the signals that are being registered with these techniques can be analyzed with respect to network characteristics such as "synchronization" and "clustering". Evidence accumulates that loss of optimal neural network architecture negatively impacts complex cerebral functioning and also decreases the threshold to develop epileptic seizures. Future research should be focused on both plasticity of neural networks and the factors that have impact on that plasticity as well as the possible role of assessment of neural network characteristics in the determination of cerebral function during the disease course.

  11. Factors Influencing Cerebral Plasticity in the Normal and Injured Brain

    PubMed Central

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

    2010-01-01

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

  12. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  13. Cognition and affective style: Individual differences in brain electrical activity during spatial and verbal tasks.

    PubMed

    Bell, Martha Ann; Fox, Nathan A

    2003-12-01

    Relations between brain electrical activity and performance on two cognitive tasks were examined in a normal population selected to be high on self-reported measures of Positive or Negative Affectivity. Twenty-five right-handed women, from an original pool of 308 college undergraduates, were the participants. EEG was recorded during baseline and during psychometrically matched spatial and verbal tasks. As predicted, participants who were high in Positive Affectivity performed equally well on the verbal and spatial tasks, while participants who were high in Negative Affectivity had spatial scores that were lower than their verbal scores. There were no group differences in baseline EEG. Both groups exhibited left central activation (i.e., alpha suppression) during the verbal and spatial tasks. When EEG data were analyzed separately for the group high in Positive Affectivity, there was evidence of parietal activation for the spatial task relative to the verbal task. The EEG data for the group high in Negative Affectivity had comparable EEG power values during verbal and spatial tasks at parietal scalp locations. These data suggest that, within a selected normal population, differences in affective style may interact with cognitive performance and with the brain electrical activity associated with that performance.

  14. Vibrotactile Discrimination Training Affects Brain Connectivity in Profoundly Deaf Individuals.

    PubMed

    González-Garrido, Andrés A; Ruiz-Stovel, Vanessa D; Gómez-Velázquez, Fabiola R; Vélez-Pérez, Hugo; Romo-Vázquez, Rebeca; Salido-Ruiz, Ricardo A; Espinoza-Valdez, Aurora; Campos, Luis R

    2017-01-01

    Early auditory deprivation has serious neurodevelopmental and cognitive repercussions largely derived from impoverished and delayed language acquisition. These conditions may be associated with early changes in brain connectivity. Vibrotactile stimulation is a sensory substitution method that allows perception and discrimination of sound, and even speech. To clarify the efficacy of this approach, a vibrotactile oddball task with 700 and 900 Hz pure-tones as stimuli [counterbalanced as target (T: 20% of the total) and non-target (NT: 80%)] with simultaneous EEG recording was performed by 14 profoundly deaf and 14 normal-hearing (NH) subjects, before and after a short training period (five 1-h sessions; in 2.5-3 weeks). A small device worn on the right index finger delivered sound-wave stimuli. The training included discrimination of pure tone frequency and duration, and more complex natural sounds. A significant P300 amplitude increase and behavioral improvement was observed in both deaf and normal subjects, with no between group differences. However, a P3 with larger scalp distribution over parietal cortical areas and lateralized to the right was observed in the profoundly deaf. A graph theory analysis showed that brief training significantly increased fronto-central brain connectivity in deaf subjects, but not in NH subjects. Together, ERP tools and graph methods depicted the different functional brain dynamic in deaf and NH individuals, underlying the temporary engagement of the cognitive resources demanded by the task. Our findings showed that the index-fingertip somatosensory mechanoreceptors can discriminate sounds. Further studies are necessary to clarify brain connectivity dynamics associated with the performance of vibrotactile language-related discrimination tasks and the effect of lengthier training programs.

  15. Vibrotactile Discrimination Training Affects Brain Connectivity in Profoundly Deaf Individuals

    PubMed Central

    González-Garrido, Andrés A.; Ruiz-Stovel, Vanessa D.; Gómez-Velázquez, Fabiola R.; Vélez-Pérez, Hugo; Romo-Vázquez, Rebeca; Salido-Ruiz, Ricardo A.; Espinoza-Valdez, Aurora; Campos, Luis R.

    2017-01-01

    Early auditory deprivation has serious neurodevelopmental and cognitive repercussions largely derived from impoverished and delayed language acquisition. These conditions may be associated with early changes in brain connectivity. Vibrotactile stimulation is a sensory substitution method that allows perception and discrimination of sound, and even speech. To clarify the efficacy of this approach, a vibrotactile oddball task with 700 and 900 Hz pure-tones as stimuli [counterbalanced as target (T: 20% of the total) and non-target (NT: 80%)] with simultaneous EEG recording was performed by 14 profoundly deaf and 14 normal-hearing (NH) subjects, before and after a short training period (five 1-h sessions; in 2.5–3 weeks). A small device worn on the right index finger delivered sound-wave stimuli. The training included discrimination of pure tone frequency and duration, and more complex natural sounds. A significant P300 amplitude increase and behavioral improvement was observed in both deaf and normal subjects, with no between group differences. However, a P3 with larger scalp distribution over parietal cortical areas and lateralized to the right was observed in the profoundly deaf. A graph theory analysis showed that brief training significantly increased fronto-central brain connectivity in deaf subjects, but not in NH subjects. Together, ERP tools and graph methods depicted the different functional brain dynamic in deaf and NH individuals, underlying the temporary engagement of the cognitive resources demanded by the task. Our findings showed that the index-fingertip somatosensory mechanoreceptors can discriminate sounds. Further studies are necessary to clarify brain connectivity dynamics associated with the performance of vibrotactile language-related discrimination tasks and the effect of lengthier training programs. PMID:28220063

  16. The neuroanatomy of prematurity: normal brain development and the impact of preterm birth.

    PubMed

    Ortinau, Cynthia; Neil, Jeffrey

    2015-03-01

    Brain development is a complex process of micro- and macrostructural events that include neuronal and glial proliferation and migration, myelination, and organizational development of cortical layers and circuitry. Recent progress in understanding these processes has provided insight into the pathophysiology of brain injury and alterations of cerebral development in preterm infants. A key factor of abnormalities in the preterm infant is the maturational stage of the brain at the time of birth. This review summarizes current data on normal brain development, patterns of brain injury in the preterm infant, and the associated axonal/neuronal disturbances that occur in the setting of this injury, often termed encephalopathy of prematurity.

  17. Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.

    PubMed

    Benignus, Vernon A; Coleman, Thomas G

    2010-04-01

    At some level, carboxyhemoglobin (COHb) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in both normal and ischemic heart patients. At high COHb levels in normal subjects, brain function is also affected and behavioral performance is impaired.These are findings from published experiments that are, due to ethical or practical considerations, incomplete in that higher or lower ranges of COHb, and exercise have not been well studied. To fill in this knowledge base, a whole-body human physiological model was used to make estimates of physiological functioning by the simulation of parametric exposures to CO and various exercise levels. Ischemic heart disease was simulated by introducing a stenosis in the left heart arterial supply. Brain blood flow was also limited by such a stenosis. To lend credibility to such estimation, the model was tested by simulating experiments from the published literature. Simulations permitted several new conclusions. Increases in COHb produced the largest decreases in exercise duration when exercise was least strenuous and when COHb was smallest. For ischemic heart disease subjects, the greatest change in exercise duration produced by COHb increase was when ischemia and COHb was smallest. Brain aerobic metabolism was unaffected until COHb exceeded 25%, unless the maximum brain blood supply was limited by a stenosis greater than 50% of normal. For higher levels of stenosis, aerobic brain metabolism was reduced for any increase in COHb level, implying that behavior would be impaired with no "threshold" for COHb.

  18. Affective Interaction with a Virtual Character Through an fNIRS Brain-Computer Interface.

    PubMed

    Aranyi, Gabor; Pecune, Florian; Charles, Fred; Pelachaud, Catherine; Cavazza, Marc

    2016-01-01

    Affective brain-computer interfaces (BCI) harness Neuroscience knowledge to develop affective interaction from first principles. In this article, we explore affective engagement with a virtual agent through Neurofeedback (NF). We report an experiment where subjects engage with a virtual agent by expressing positive attitudes towards her under a NF paradigm. We use for affective input the asymmetric activity in the dorsolateral prefrontal cortex (DL-PFC), which has been previously found to be related to the high-level affective-motivational dimension of approach/avoidance. The magnitude of left-asymmetric DL-PFC activity, measured using functional near infrared spectroscopy (fNIRS) and treated as a proxy for approach, is mapped onto a control mechanism for the virtual agent's facial expressions, in which action units (AUs) are activated through a neural network. We carried out an experiment with 18 subjects, which demonstrated that subjects are able to successfully engage with the virtual agent by controlling their mental disposition through NF, and that they perceived the agent's responses as realistic and consistent with their projected mental disposition. This interaction paradigm is particularly relevant in the case of affective BCI as it facilitates the volitional activation of specific areas normally not under conscious control. Overall, our contribution reconciles a model of affect derived from brain metabolic data with an ecologically valid, yet computationally controllable, virtual affective communication environment.

  19. Affective Interaction with a Virtual Character Through an fNIRS Brain-Computer Interface

    PubMed Central

    Aranyi, Gabor; Pecune, Florian; Charles, Fred; Pelachaud, Catherine; Cavazza, Marc

    2016-01-01

    Affective brain-computer interfaces (BCI) harness Neuroscience knowledge to develop affective interaction from first principles. In this article, we explore affective engagement with a virtual agent through Neurofeedback (NF). We report an experiment where subjects engage with a virtual agent by expressing positive attitudes towards her under a NF paradigm. We use for affective input the asymmetric activity in the dorsolateral prefrontal cortex (DL-PFC), which has been previously found to be related to the high-level affective-motivational dimension of approach/avoidance. The magnitude of left-asymmetric DL-PFC activity, measured using functional near infrared spectroscopy (fNIRS) and treated as a proxy for approach, is mapped onto a control mechanism for the virtual agent’s facial expressions, in which action units (AUs) are activated through a neural network. We carried out an experiment with 18 subjects, which demonstrated that subjects are able to successfully engage with the virtual agent by controlling their mental disposition through NF, and that they perceived the agent’s responses as realistic and consistent with their projected mental disposition. This interaction paradigm is particularly relevant in the case of affective BCI as it facilitates the volitional activation of specific areas normally not under conscious control. Overall, our contribution reconciles a model of affect derived from brain metabolic data with an ecologically valid, yet computationally controllable, virtual affective communication environment. PMID:27462216

  20. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    NASA Astrophysics Data System (ADS)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  1. High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging.

    PubMed

    Harris, Janna L; Yeh, Hung-Wen; Swerdlow, Russell H; Choi, In-Young; Lee, Phil; Brooks, William M

    2014-07-01

    Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging.

  2. [The shrinking brain: result of normal aging or of selection bias in research?].

    PubMed

    Burgmans, S; van Boxtel, M P J

    2012-02-01

    The volume of our brain decreases as we age. This has been demonstrated by several large studies on normal aging. A recent study indicates, however, that the extent of this decline in normal aging probably has been overestimated because these studies have included subjects with preclinical disorders. In this article, an example from science is used to describe what effect selection bias may have on our model of the aging brain.

  3. Family poverty affects the rate of human infant brain growth.

    PubMed

    Hanson, Jamie L; Hair, Nicole; Shen, Dinggang G; Shi, Feng; Gilmore, John H; Wolfe, Barbara L; Pollak, Seth D

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

  4. Family Poverty Affects the Rate of Human Infant Brain Growth

    PubMed Central

    Hanson, Jamie L.; Hair, Nicole; Shen, Dinggang G.; Shi, Feng; Gilmore, John H.; Wolfe, Barbara L.; Pollak, Seth D.

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  5. Do brain lesions in stroke affect basic emotions and attachment?

    PubMed

    Farinelli, Marina; Panksepp, Jaak; Gestieri, Laura; Maffei, Monica; Agati, Raffaele; Cevolani, Daniela; Pedone, Vincenzo; Northoff, Georg

    2015-01-01

    The aim of the current study was to investigate basic emotions and attachment in a sample of 86 stroke patients. We included a control group of 115 orthopedic patients (matched for age and cognitive status) without brain lesions to control for unspecific general illness effects of a traumatic recent event on basic emotions and attachment. In order to measure basic emotions and attachment style we applied the Affective Neuroscience Personality Scale (ANPS) and the Attachment Style Questionnaire (ASQ). The stroke patients showed significantly different scores in the SEEKING, SADNESS, and ANGER subscales of the ANPS as well as in the Relationship as Secondary Attachment dimension of the ASQ when compared to the control group. These differences show a pattern influenced by lesion location mainly as concerns basic emotions. Anterior, medial, left, and subcortical patients provide scores significantly lower in ANPS-SEEKING than the control group; ANPS-SADNESS scores in anterior, right, medial, and subcortical patients were significantly higher than those of the control group. ANPS-ANGER scores in posterior, right, and lateral patients were significantly higher than those in the control group; finally, the ANPS-FEAR showed slightly lower scores in posterior patients than in the control group. Minor effects on brain lesions were also individuated in the attachment style. Anterior lesion patients showed a significantly higher average score in the ASQ-Need for Approval subscale than the control group. ASQ-Confidence subscale scores differed significantly in stroke patients with lesions in medial brain regions when compared to control subjects. Scores at ANPS and ASQ subscales appear significantly more correlated in stroke patients than in the control group. Such finding of abnormalities, especially concerning basic emotions in stroke brain-lesioned patients, indicates that the effect of brain lesions may enhance the interrelation between basic emotions and attachment with

  6. The Ventricular System of the Brain: Anatomy and Normal Variations.

    PubMed

    Stratchko, Lindsay; Filatova, Irina; Agarwal, Amit; Kanekar, Sangam

    2016-04-01

    The cerebral ventricular system is intimately associated with the forebrain and brainstem. The ventricular system functions to produce and circulate cerebrospinal fluid, which plays an important role in mechanical protection and regulation of homeostasis in the central nervous system. This article discusses anatomy and neuroimaging of the ventricular system and highlights normal anatomical variations that may be mistaken for pathology. Applied surgical anatomy is reviewed with emphasis on operative approach and potential risk to adjacent central nervous system structures.

  7. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  8. Functional Modularity of Background Activities in Normal and Epileptic Brain Networks

    NASA Astrophysics Data System (ADS)

    Chavez, M.; Valencia, M.; Navarro, V.; Latora, V.; Martinerie, J.

    2010-03-01

    We analyze the connectivity structure of weighted brain networks extracted from spontaneous magnetoencephalographic signals of healthy subjects and epileptic patients (suffering from absence seizures) recorded at rest. We find that, for the activities in the 5-14 Hz range, healthy brains exhibit a sparse connectivity, whereas the brain networks of patients display a rich connectivity with a clear modular structure. Our results suggest that modularity plays a key role in the functional organization of brain areas during normal and pathological neural activities at rest.

  9. Brain gray and white matter differences in healthy normal weight and obese children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To compare brain gray and white matter development in healthy normal weight and obese children. Twenty-four healthy 8- to 10-year-old children whose body mass index was either <75th percentile (normal weight) or >95th percentile (obese) completed an MRI examination which included T1-weighted three-d...

  10. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  11. Use of deep brain stimulation for major affective disorders

    PubMed Central

    Mi, Kuanqing

    2016-01-01

    The multifactorial etiology of major affective disorders, such as major depression and bipolar disorder, poses a challenge for identification of effective treatments. In a substantial number of patients, psychopharmacologic treatment does not lead to effective continuous symptom relief. The use of deep brain stimulation (DBS) for treatment-resistant patients is an investigational approach that has recently produced promising results. The recent development of safer stereotaxic neurosurgery, and the combination with functional neuroimaging to map the affected brain circuits, have led to the investigation of DBS as a potential strategy to treat major mood disorders. Several independent clinical studies have recently shown that chronic DBS treatment leads to remission of symptoms in a high number of treatment-resistant patients for major depression and bipolar disorder. In conclusion, the existing proof-of-principle that DBS can be an effective intervention for treatment-resistant depression opens new avenues for treatment. However, multicenter, randomized and blind trials need to confirm efficacy and be approved after the most recent failures. Patient selection and surgical-related improvements are key issues that remain to be addressed to help deliver more precise and customized treatment. PMID:27698736

  12. An Update of the Classical and Novel Methods Used for Measuring Fast Neurotransmitters During Normal and Brain Altered Function

    PubMed Central

    Cifuentes Castro, Victor Hugo; López Valenzuela, Carmen Lucía; Salazar Sánchez, Juan Carlos; Peña, Kenia Pardo; López Pérez, Silvia J.; Ibarra, Jorge Ortega; Villagrán, Alberto Morales

    2014-01-01

    To understand better the cerebral functions, several methods have been developed to study the brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role to know better how the brain works during normal or pathological conditions, as well as for studying the changes in neurotransmitter concentration with the use of several drugs that could affect or reestablish the normal brain activity. Immediate response of the brain to environmental conditions is related with the release of the fast acting neurotransmission by glutamate (Glu), γ-aminobutyric acid (GABA) and acetylcholine (ACh) through the opening of ligand-operated ion channels. Neurotransmitter release is mainly determined by the classical microdialysis technique, this is generally coupled to high performance liquid chromatography (HPLC). Detection of neurotransmitters can be done by fluorescence, optical density, electrochemistry or other detection systems more sophisticated. Although the microdialysis method is the golden technique to monitor the brain neurotransmitters, it has a poor temporal resolution. Recently, with the use of biosensor the drawback of temporal resolution has been improved considerably, however other inconveniences have merged, such as stability, reproducibility and the lack of reliable biosensors mainly for GABA. The aim of this review is to show the important advances in the different ways to measure neurotransmitter concentrations; both with the use of classic techniques as well as with the novel methods and alternant approaches to improve the temporal resolution. PMID:25977677

  13. The impoverished brain: disparities in maternal education affect the neural response to sound.

    PubMed

    Skoe, Erika; Krizman, Jennifer; Kraus, Nina

    2013-10-30

    Despite the prevalence of poverty worldwide, little is known about how early socioeconomic adversity affects auditory brain function. Socioeconomically disadvantaged children are underexposed to linguistically and cognitively stimulating environments and overexposed to environmental toxins, including noise pollution. This kind of sensory impoverishment, we theorize, has extensive repercussions on how the brain processes sound. To characterize how this impoverishment affects auditory brain function, we compared two groups of normal-hearing human adolescents who attended the same schools and who were matched in age, sex, and ethnicity, but differed in their maternal education level, a correlate of socioeconomic status (SES). In addition to lower literacy levels and cognitive abilities, adolescents from lower maternal education backgrounds were found to have noisier neural activity than their classmates, as reflected by greater activity in the absence of auditory stimulation. Additionally, in the lower maternal education group, the neural response to speech was more erratic over repeated stimulation, with lower fidelity to the input signal. These weaker, more variable, and noisier responses are suggestive of an inefficient auditory system. By studying SES within a neuroscientific framework, we have the potential to expand our understanding of how experience molds the brain, in addition to informing intervention research aimed at closing the achievement gap between high-SES and low-SES children.

  14. Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities: case report

    PubMed Central

    2007-01-01

    Background It has recently become evident that circulating thyroid antibodies are found in excess among patients suffering from mood disorders. Moreover, a manic episode associated with Hashimoto's thyroiditis has recently been reported as the first case of bipolar disorder due to Hashimoto's encephalopathy. We report a case in which Hashimoto's thyroiditis was suspected to be involved in the deteriorating course of mood disorder and discuss potential pathogenic mechanisms linking thyroid autoimmunity with psychopathology. Case presentation A 43-year-old woman, with a history of recurrent depression since the age of 31, developed manic, psychotic, and soft neurological symptoms across the last three years in concomitance with her first diagnosis of Hashimoto's thyroiditis. The patient underwent a thorough medical and neurological workup. Circulating thyroperoxidase antibodies were highly elevated but thyroid function was adequately maintained with L-thyroxine substitution. EEG was normal and no other signs of current CNS inflammation were evidenced. However, brain magnetic resonance imaging evidenced several non-active lesions in the white matter from both hemispheres, suggestive of a non-specific past vasculitis. Brain single-photon emission computed tomography showed cortical perfusion asymmetry particularly between frontal lobes. Conclusion We hypothesize that abnormalities in cortical perfusion might represent a pathogenic link between thyroid autoimmunity and mood disorders, and that the rare cases of severe Hashimoto's encephalopathy presenting with mood disorder might be only the tip of an iceberg. PMID:18096026

  15. Intracranial cerebrospinal fluid measurement studies in suspected idiopathic normal pressure hydrocephalus, secondary normal pressure hydrocephalus, and brain atrophy

    PubMed Central

    Tsunoda, A; Mitsuoka, H; Bandai, H; Endo, T; Arai, H; Sato, K

    2002-01-01

    Objective: To investigate intracranial cerebrospinal fluid (CSF) distribution in patients with a clinical diagnosis of idiopathic normal pressure hydrocephalus (INPH). Methods: 24 patients with a clinical diagnosis of INPH were studied. Control groups comprised 17 patients with secondary normal pressure hydrocephalus (SNPH), 21 patients with brain atrophy, and 18 healthy volunteers. Ventricular volume (VV) and intracranial CSF volume (ICV) were measured using a magnetic resonance based method and the VV/ICV ratio was calculated. Results: The SNPH group showed a marked increase in the VV/ICV ratio compared with the healthy volunteers (37.8% v 15.6%, p < 0.0001). The brain atrophy group showed a significant increase in ICV compared with the healthy volunteers (284.4 ml v 194.7 ml, p =0.0002). The INPH group showed an increase in ICV (281.2 ml, p = 0.0002) and an increase in the VV/ICV ratio (38.0%, p < 0.0001). Fifteen of 24 INPH patients underwent shunting; 11 improved and four did not. Conclusions: The results suggest that INPH patients have brain atrophy in addition to hydrocephalic features. This may help to explain the difficulties encountered in the diagnosis and the unpredictable response rate to shunt surgery in INPH patients. PMID:12397150

  16. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  17. Changes in topological organization of functional PET brain network with normal aging.

    PubMed

    Liu, Zhiliang; Ke, Lining; Liu, Huafeng; Huang, Wenhua; Hu, Zhenghui

    2014-01-01

    Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of 90 regions in younger (mean age 36.5 years) and older (mean age 56.3 years) age groups with PET data. 113 younger and 110 older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of 90 regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging.

  18. Changes in Topological Organization of Functional PET Brain Network with Normal Aging

    PubMed Central

    Liu, Huafeng; Huang, Wenhua; Hu, Zhenghui

    2014-01-01

    Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of regions in younger (mean age years) and older (mean age years) age groups with PET data. younger and older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging. PMID:24586370

  19. Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development.

    PubMed

    Ghosh, Payel; Mukherjee, Nabanita; Ghosh, Krishnendu; Mallick, Suvadip; Pal, Chiranjib; Laskar, Aparna; Ghosh, Anirban

    2015-09-01

    The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed.

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

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

    SciTech Connect

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

    2009-03-10

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

  2. The brain's emotional foundations of human personality and the Affective Neuroscience Personality Scales.

    PubMed

    Davis, Kenneth L; Panksepp, Jaak

    2011-10-01

    Six of the primary-process subcortical brain emotion systems - SEEKING, RAGE, FEAR, CARE, GRIEF and PLAY - are presented as foundational for human personality development, and hence as a potentially novel template for personality assessment as in the Affective Neurosciences Personality Scales (ANPS), described here. The ANPS was conceptualized as a potential clinical research tool, which would help experimentalists and clinicians situate subjects and clients in primary-process affective space. These emotion systems are reviewed in the context of a multi-tiered framing of consciousness spanning from primary affect, which encodes biological valences, to higher level tertiary (thought mediated) processing. Supporting neuroscience research is presented along with comparisons to Cloninger's Temperament and Character Inventory and the Five Factor Model (FFM). Suggestions are made for grounding the internal structure of the FFM on the primal emotional systems recognized in affective neuroscience, which may promote substantive dialog between human and animal research traditions. Personality is viewed in the context of Darwinian "continuity" with the inherited subcortical brain emotion systems being foundational, providing major forces for personality development in both humans and animals, and providing an affective infrastructure for an expanded five factor descriptive model applying to normal and clinical human populations as well as mammals generally. Links with ontogenetic and epigenetic models of personality development are also presented. Potential novel clinical applications of the CARE maternal-nurturance system and the PLAY system are also discussed.

  3. Channels of the corpus callosum. Evidence from simple reaction times to lateralized flashes in the normal and the split brain.

    PubMed

    Iacoboni, M; Zaidel, E

    1995-06-01

    We studied 75 normal subjects and three commissurotomized patients using unimanual simple reaction times to lateralized flashes as a behavioural estimate of interhemispheric transmission time. Three different versions of the paradigm were performed: (i) the basic task; (ii) a motor task, with an increased complexity of the motor response; and (iii) a visual task, with an increased complexity of the visual stimulus presentation. We tested two hypotheses. First, that the new versions of the simple reaction time task result in shifts in hemispheric specialization for processing motor output (indicated by a main effect of response hand) or visual input (indicated by a main effect of visual field) alone, without affecting callosal transmission. In that case normals and split brain patients would show no significant task by response hand by visual field interaction and no significant task by crossed-uncrossed difference interaction. Secondly, that the new versions of the task affect callosal transfer. In that case, normals, but not split brain patients, would show a significant task by response hand by visual field interaction and a significant task by crossed-uncrossed difference interaction. Results are consistent with the latter hypothesis, showing that the motor task significantly changed the response hand by visual field interaction and the crossed-uncrossed difference, but only in normal subjects, perhaps producing a switch in the callosal channel subserving the interhemispheric transfer.

  4. HRT and its effect on normal ageing of the brain and dementia

    PubMed Central

    Compton, Jacqueline; van Amelsvoort, Therese; Murphy, Declan

    2001-01-01

    There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD. PMID:11736875

  5. Timing of light exposure affects mood and brain circuits

    PubMed Central

    Bedrosian, T A; Nelson, R J

    2017-01-01

    Temporal organization of physiology is critical for human health. In the past, humans experienced predictable periods of daily light and dark driven by the solar day, which allowed for entrainment of intrinsic circadian rhythms to the environmental light–dark cycles. Since the adoption of electric light, however, pervasive exposure to nighttime lighting has blurred the boundaries of day and night, making it more difficult to synchronize biological processes. Many systems are under circadian control, including sleep–wake behavior, hormone secretion, cellular function and gene expression. Circadian disruption by nighttime light perturbs those processes and is associated with increasing incidence of certain cancers, metabolic dysfunction and mood disorders. This review focuses on the role of artificial light at night in mood regulation, including mechanisms through which aberrant light exposure affects the brain. Converging evidence suggests that circadian disruption alters the function of brain regions involved in emotion and mood regulation. This occurs through direct neural input from the clock or indirect effects, including altered neuroplasticity, neurotransmission and clock gene expression. Recently, the aberrant light exposure has been recognized for its health effects. This review summarizes the evidence linking aberrant light exposure to mood. PMID:28140399

  6. Timing of light exposure affects mood and brain circuits.

    PubMed

    Bedrosian, T A; Nelson, R J

    2017-01-31

    Temporal organization of physiology is critical for human health. In the past, humans experienced predictable periods of daily light and dark driven by the solar day, which allowed for entrainment of intrinsic circadian rhythms to the environmental light-dark cycles. Since the adoption of electric light, however, pervasive exposure to nighttime lighting has blurred the boundaries of day and night, making it more difficult to synchronize biological processes. Many systems are under circadian control, including sleep-wake behavior, hormone secretion, cellular function and gene expression. Circadian disruption by nighttime light perturbs those processes and is associated with increasing incidence of certain cancers, metabolic dysfunction and mood disorders. This review focuses on the role of artificial light at night in mood regulation, including mechanisms through which aberrant light exposure affects the brain. Converging evidence suggests that circadian disruption alters the function of brain regions involved in emotion and mood regulation. This occurs through direct neural input from the clock or indirect effects, including altered neuroplasticity, neurotransmission and clock gene expression. Recently, the aberrant light exposure has been recognized for its health effects. This review summarizes the evidence linking aberrant light exposure to mood.

  7. How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

  8. β-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals

    PubMed Central

    Fletcher, Evan; Villeneuve, Sylvia; Maillard, Pauline; Harvey, Danielle; Reed, Bruce; Jagust, William; DeCarli, Charles

    2016-01-01

    Recent literature has examined baseline hippocampal volume and extent of brain amyloidosis to test potential synergistic effects on worsening cognition and extent of brain atrophy. Use of hippocampal volume in prior studies was based on the notion that limbic circuit degeneration is an early manifestation of the Alzheimer's Disease (AD) pathophysiology. To clarify these interactions early in the AD process, we tested the effects of amyloid and baseline normalized hippocampal volume on longitudinal brain atrophy rates in a group of cognitively normal individuals. Results showed that the combination of elevated β-amyloid and baseline hippocampal atrophy is associated with increased rates specific to the limbic circuit and splenium. Importantly, this atrophy pattern emerged from a voxelwise analysis, corroborated by regression models over ROIs in native space. The results are broadly consistent with previous studies of the effects of amyloid and baseline hippocampal atrophy in normals, while pointing to accelerated atrophy of AD-vulnerable regions detectable at the preclinical stage. PMID:26973117

  9. Computed tomography of the brain stem with intrathecal metrizamide. Part 1: the normal brain stem

    SciTech Connect

    Mawad, M.E.; Silver, A.J.; Hilal, S.K.; Ganti, S.R.

    1983-03-01

    Detailed anatomy of the brain stem and cervicomedullary junction can be accurately demonstrated with metrizamide computed tomographic cisternography. Specifically surface anatomy is unusually well outlined. Nine distinct and easily recognizable levels of section are described: four levels in the medulla, three in the pons, and two in the mesencephalon. Surface features of the brain stem, fine details in the floor of the fourth ventricle, cranial nerves, and vascular structures are shown and discussed.

  10. Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

    ERIC Educational Resources Information Center

    Hawley, Theresa

    Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

  11. Astrocyte activation is suppressed in both normal and injured brain by FGF signaling

    PubMed Central

    Kang, Wenfei; Balordi, Francesca; Su, Nan; Chen, Lin; Fishell, Gordon; Hébert, Jean M.

    2014-01-01

    In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss- and gain-of-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets. PMID:25002516

  12. Neuroprotective pathways: lifestyle activity, brain pathology, and cognition in cognitively normal older adults.

    PubMed

    Wirth, Miranka; Haase, Claudia M; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J

    2014-08-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within the brain regions affected in Alzheimer's disease (AD). Ninety-two cognitively normal older adults (75.2 ± 5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using [(11)C] labeled Pittsburgh-Compound-B positron emission tomography), cerebrovascular lesions (using magnetic resonance imaging-defined white matter lesion [WML]), and neural integrity within AD regions (using a multimodal neuroimaging biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower [(11)C] labeled Pittsburgh-Compound-B retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development.

  13. Neuroprotective Pathways: Lifestyle activity, brain pathology and cognition in cognitively normal older adults

    PubMed Central

    Wirth, Miranka; Haase, Claudia M.; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J.

    2014-01-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within brain regions affected in Alzheimer’s disease (AD). Ninety-two cognitively normal older adults (75.2±5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using PIB-PET), cerebrovascular lesions (using MRI-defined white matter lesion (WML)), and neural integrity within AD regions (using a multimodal biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower PIB retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development. PMID:24656834

  14. Association of Mild Kidney Dysfunction with Silent Brain Lesions in Neurologically Normal Subjects

    PubMed Central

    Toyoda, Genya; Bokura, Hirokazu; Mitaki, Shingo; Onoda, Keiichi; Oguro, Hiroaki; Nagai, Atsushi; Yamaguchi, Shuhei

    2015-01-01

    Background Chronic kidney disease (CKD) has been closely associated with stroke. Although a large number of studies reported the relationship between CKD and different types of asymptomatic brain lesions, few comprehensive analyses have been performed for all types of silent brain lesions. Methods We performed a cross-sectional study involving 1,937 neurologically normal subjects (mean age 59.4 years). Mild CKD was defined as an estimated glomerular filtration rate between 30 and 60 ml/min/1.73 m2 or positive proteinuria. Results The prevalence of mild CKD was 8.7%. Univariate analysis revealed an association between CKD and all silent brain lesions, including silent brain infarction, periventricular hyperintensity, subcortical white matter lesion, and microbleeds, in addition to hypertension and diabetes mellitus after adjusting for age and sex. In binary logistic regression analysis, the presence of CKD was a significant risk factor for all types of silent brain lesions, independent of other risk factors. Conclusions These results suggest that mild CKD is independently associated with all types of silent brain lesions, even in neurologically normal subjects. PMID:25873927

  15. Intrinsic functional connectivity pattern-based brain parcellation using normalized cut

    NASA Astrophysics Data System (ADS)

    Cheng, Hewei; Song, Dandan; Wu, Hong; Fan, Yong

    2012-02-01

    In imaging data based brain network analysis, a necessary precursor for constructing meaningful brain networks is to identify functionally homogeneous regions of interest (ROIs) for defining network nodes. For parcellating the brain based on resting state fMRI data, normalized cut is one widely used clustering algorithm which groups voxels according to the similarity of functional signals. Due to low signal to noise ratio (SNR) of resting state fMRI signals, spatial constraint is often applied to functional similarity measures to generate smooth parcellation. However, improper spatial constraint might alter the intrinsic functional connectivity pattern, thus yielding biased parcellation results. To achieve reliable and least biased parcellation of the brain, we propose an optimization method for the spatial constraint to functional similarity measures in normalized cut based brain parcellation. Particularly, we first identify the space of all possible spatial constraints that are able to generate smooth parcellation, then find the spatial constraint that leads to the brain parcellation least biased from the intrinsic function pattern based parcellation, measured by the minimal Ncut value calculated based on the functional similarity measure of original functional signals. The proposed method has been applied to the parcellation of medial superior frontal cortex for 20 subjects based on their resting state fMRI data. The experiment results indicate that our method can generate meaningful parcellation results, consistent with existing functional anatomy knowledge.

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

    PubMed Central

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

    2016-01-01

    The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework. PMID:27910866

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

    PubMed

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

    2016-12-02

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

  18. Consistency of Intermanual Discrepancies in Normal and Unilateral Brain Lesion Patients.

    ERIC Educational Resources Information Center

    Bornstein, R. A.

    1986-01-01

    The distribution of intermanual discrepancies on three motor tests (Grooved Pegboard, Finger Tapping and Dynamometer) were examined in normal and unilateral brain lesion samples. Considerable variability in the intermanual discrepancies was observed in all three samples. Therefore, the consistency of discrepancies across tasks was examined. The…

  19. Confirmation of Correlation between Brain Nerve Conduction Velocity and Intelligence Level in Normal Adults

    ERIC Educational Resources Information Center

    Reed, T. Edward; Vernon, Philip A.; Johnson, Andrew M.

    2004-01-01

    In 1992, Reed and Jensen ["Intelligence" 16 (1992) 259-272] reported a positive correlation (0.26; "p"= 0.002; 0.37 after correcting for restricted intelligence range) between a brain nerve conduction velocity (NCV) and intelligence level in 147 normal male students. In the first follow-up of their study, we report on a study…

  20. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain.

    PubMed

    Barrett, Lisa Feldman; Satpute, Ajay Bhaskar

    2013-06-01

    Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain.

  1. Trajectories of cortical surface area and cortical volume maturation in normal brain development

    PubMed Central

    Ducharme, Simon; Albaugh, Matthew D.; Nguyen, Tuong-Vi; Hudziak, James J.; Mateos-Pérez, J.M.; Labbe, Aurelie; Evans, Alan C.; Karama, Sherif

    2015-01-01

    This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1–3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article “Trajectories of cortical thickness maturation in normal brain development – the importance of quality control procedures” (Ducharme et al., 2015) [1]. PMID:26702424

  2. Normal Brain-Skull Development with Hybrid Deformable VR Models Simulation.

    PubMed

    Jin, Jing; De Ribaupierre, Sandrine; Eagleson, Roy

    2016-01-01

    This paper describes a simulation framework for a clinical application involving skull-brain co-development in infants, leading to a platform for craniosynostosis modeling. Craniosynostosis occurs when one or more sutures are fused early in life, resulting in an abnormal skull shape. Surgery is required to reopen the suture and reduce intracranial pressure, but is difficult without any predictive model to assist surgical planning. We aim to study normal brain-skull growth by computer simulation, which requires a head model and appropriate mathematical methods for brain and skull growth respectively. On the basis of our previous model, we further specified suture model into fibrous and cartilaginous sutures and develop algorithm for skull extension. We evaluate the resulting simulation by comparison with datasets of cases and normal growth.

  3. Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI

    PubMed Central

    Labiano-Fontcuberta, Andrés; Mato-Abad, Virginia; Álvarez-Linera, Juan; Hernández-Tamames, Juan Antonio; Martínez-Ginés, María Luisa; Aladro, Yolanda; Ayuso, Lucía; Domingo-Santos, Ángela; Benito-León, Julián

    2016-01-01

    Abstract To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (–3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity. PMID:27399108

  4. Genetic defects in folate and cobalamin pathways affecting the brain.

    PubMed

    Kirsch, Susanne H; Herrmann, Wolfgang; Obeid, Rima

    2013-01-01

    Folate and cobalamin are necessary for early brain development and function. Deficiency of folate or cobalamin during pregnancy can cause severe malformation in the central nervous system such as neural tube defects. After birth, folate and cobalamin deficiency can cause anemia, failure to thrive, recurrent infections, psychiatric and neurological symptoms. The folate and the homocysteine metabolic pathways interact at a central step where 5-methyltetrahydrofolate donates its methyl group to homocysteine to produce methionine and tetrahydrofolate. Methyl cobalamin and folate interact at this critical step. Both nutrients have a crucial role in DNA synthesis and in delivering S-adenosylmethionine, the universal methyl donor. Severe and mild inherited disorders in folate and cobalamin pathways have been described. The two groups of disorders share some similarities, but differ in the molecular mechanism, metabolic dysregulation, and disease management. This review summarizes selected disorders, including rare and common mutations that affect folate and cobalamin absorption, transport, or dependent enzymes. When the mutations are discovered early enough, many of the described disorders are easily treatable by B vitamin supplementation, which often prevents or reverses the manifestation of the disease. Therefore, the screening for mutations is recommended and should be carried out as early as possible: after occurrence of the first symptoms or when a certain constellations of the folate and cobalamin related markers are measured, such as elevated homocysteine and/or methylmalonic acid.

  5. R2* mapping for brain iron: associations with cognition in normal aging.

    PubMed

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined.

  6. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  7. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    SciTech Connect

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  8. Doses delivered to normal brain under different treatment protocols at Brookhaven National Laboratory

    SciTech Connect

    Capala, J.; Coderre, J.A.; Liu, H.B.

    1996-12-31

    As of October 31, 1996, 23 glioblastoma multiforme patients underwent BNCT under several treatment protocols at the Brookhaven Medical Research Reactor. For treatment planning and dosimetry purposes, these protocols may be divided into four groups. The first group comprises protocols that used an 8-cm collimator and allowed a peak normal brain dose of 10.5 Gy-Eq to avolume of 1 cm{sup 3} were the thermal neutron flux was maximal (even if it happened to be in the tumor volume). The second group differs from the first in that it allowed a peak normal brain dose of 12.6 Gy-Eq. The protocols of the third and fourth groups allowed the prescribed peak normal brain dose of 12.6 Gy-Eq to be outside of the tumor volume, used a 12-cm collimator and, respectively, uni- or bilateral irradiations. We describe the treatment planning procedures and report the doses delivered to various structures of the brain.

  9. Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

    PubMed Central

    Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

    2015-01-01

    Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the

  10. Magnetic Resonance Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus

    PubMed Central

    N, Fattahi; A, Arani; A, Perry; F, Meyer; A, Manduca; K, Glaser; ML, Senjem; RL, Ehman; J, Huston

    2015-01-01

    Introduction Normal pressure hydrocephalus (NPH) is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, there are multiple overlapping symptoms which often make it difficult to differentiate NPH from other types of dementia and improved diagnostic techniques would help patient management. MR elastography (MRE) is a novel diagnostic tool that could potentially identify patients with NPH. The purpose of this study was to assess brain stiffness changes in NPH patients compared with age- and sex-matched cognitively normal individuals. Methods MRE was performed on 10 NPH patients and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MRI scanner. Shear waves with 60Hz vibration frequency were transmitted into the brain by a pillow-like passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. Results A significant increase in stiffness was observed in the cerebrum (p = 0.001), occipital lobe (p = 0.0002), parietal lobe (p= 0.001), and the temporal lobe (p = 0.02) in the NPH group compared with normal controls. However, no significant difference was noted in other regions of the brain including the frontal lobe (p = 0.07), deep gray and white matter (p = 0.43), or the cerebellum (p = 0.20). Conclusion This study demonstrates increased brain stiffness in NPH patients compared to age- and sex-matched normal controls which motivates future studies investigating the use of MRE for NPH diagnosis and efficacy of shunt therapy. PMID:26542235

  11. Mapping metals in Parkinson's and normal brain using rapid-scanning x-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Popescu, Bogdan F. Gh; George, Martin J.; Bergmann, Uwe; Garachtchenko, Alex V.; Kelly, Michael E.; McCrea, Richard P. E.; Lüning, Katharina; Devon, Richard M.; George, Graham N.; Hanson, Akela D.; Harder, Sheri M.; Chapman, L. Dean; Pickering, Ingrid J.; Nichol, Helen

    2009-02-01

    Rapid-scanning x-ray fluorescence (RS-XRF) is a synchrotron technology that maps multiple metals in tissues by employing unique hardware and software to increase scanning speed. RS-XRF was validated by mapping and quantifying iron, zinc and copper in brain slices from Parkinson's disease (PD) and unaffected subjects. Regions and structures in the brain were readily identified by their metal complement and each metal had a unique distribution. Many zinc-rich brain regions were low in iron and vice versa. The location and amount of iron in brain regions known to be affected in PD agreed with analyses using other methods. Sample preparation is simple and standard formalin-fixed autopsy slices are suitable. RS-XRF can simultaneously and non-destructively map and quantify multiple metals and holds great promise to reveal metal pathologies associated with PD and other neurodegenerative diseases as well as diseases of metal metabolism.

  12. Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain.

    PubMed

    Murray, Helen C; Low, Victoria F; Swanson, Molly E V; Dieriks, Birger V; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2016-08-25

    Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology.

  13. Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring.

    PubMed

    Pallarés, M E; Adrover, E; Imsen, M; González, D; Fabre, B; Mesch, V; Baier, C J; Antonelli, M C

    2014-10-10

    We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain

  14. Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

    SciTech Connect

    Fike, J.R.; Gobbel, G.T.; Chou, D.

    1995-07-15

    The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal {sup 125}I irradiation of normal brain, and to determine the effects of an intravenous infusion of {alpha}-defluoromethylornithine (DFMO) on those responses. Adult beagle dogs were irradiated using high activity {sup 125}I sources. Cellular responses were quantified using a histomorphometric analysis. After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. {alpha}-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm{sup 2} were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury. 57 refs., 6 figs.

  15. Normal Organ Weights in Women: Part II-The Brain, Lungs, Liver, Spleen, and Kidneys.

    PubMed

    Molina, D Kimberley; DiMaio, Vincent J M

    2015-09-01

    Organomegaly can be a sign of disease and pathology, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human females. A prospective study was undertaken of healthy females who had sudden, traumatic deaths at age 18 to 35 years. Cases were excluded if there was a history of medical illness including illicit drug use, prolonged medical treatment was performed, there was a prolonged period between the time of injury and death, body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ that could have affected the weight. A total of 102 cases met criteria for inclusion in the study during the approximately 10-year period of data collection from 2004 to 2014. The decedents had an average age of 24.4 years and ranged in length from 141 to 182 cm (56.4-72.8 inches) with an average length of 160 cm (64 inches). The weight ranged from 35.9 to 152 kg (79-334 lb) with an average weight of 65.3 kg (143 lb). The majority of the decedents (86%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean brain weight was 1233 g (range, 1000-1618 g); liver mean weight, 1288 g (range, 775-2395 g); spleen mean weight, 115 g (range, 51-275 g); right lung mean weight, 340 g (range, 142-835 g); left lung mean, 299 g (range, 108-736 g); right kidney mean weight, 108 g (range, 67-261 g); and the left kidney mean weight, 116 g (range, 55-274 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors therefore propose establishing a reference range for organ weights in

  16. Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys.

    PubMed

    Molina, D Kimberley; DiMaio, Vincent J M

    2012-12-01

    Organomegaly can be a sign of disease and pathologic abnormality, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human males. A prospective study of healthy men aged 18 to 35 years who died of sudden, traumatic deaths was undertaken. Cases were excluded if there was a history of medical illness including illicit drug use, if prolonged medical treatment was performed, if there was a prolonged period between the time of injury and death, if body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ, which could have affected the weight. A total of 232 cases met criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had a mean age of 23.9 years and ranged in length from 146 to 193 cm, with a mean length of 173 cm. The weight ranged from 48.5 to 153 kg, with a mean weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean weight of the brain was 1407 g (range, 1070-1767 g), that of the liver was 1561 g (range, 838-2584 g), that of the spleen was 139 g (range, 43-344 g), that of the right lung was 445 g (range, 185-967 g), that of the left lung was 395 g (range, 186-885 g), that of the right kidney was 129 g (range, 79-223 g), and that of the left kidney was 137 g (range, 74-235 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors, therefore, propose establishing a reference range for organ weights in men, much like those in use

  17. Calbindin distribution in cortical and subcortical brain structures of normal and rabies-infected mice.

    PubMed

    Torres-Fernández, Orlando; Yepes, Gloria E; Gómez, Javier E; Pimienta, Hernán J

    2005-10-01

    Rabies has been an enigmatic disease of the nervous system because microscopic findings in the brain tissue are not paralleled by the severity of the clinical illness. The calcium binding protein calbindin (CB) is a neuronal marker of great interest in neuroanatomy and neuropathology. CB-ir neurons in the striatum and cerebral cortex are gabaergic cells. In the present work CB-immunoreactivity was evaluated in brains of normal and rabies-infected mice. Rabies infection caused loss of CB-immunostaining in the cortical supragranular layers as well as in the striatum. Loss of CB in the brains of mice infected with rabies virus can produce impairment in Ca++ homeostasis and in the gabaergic neurotransmission.

  18. Classification of normal and pathological aging processes based on brain MRI morphology measures

    NASA Astrophysics Data System (ADS)

    Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.

    2014-03-01

    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.

  19. CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

    PubMed

    Bradley, W G

    2015-05-01

    CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood.

  20. Early Folding Patterns and Asymmetries of the Normal Human Brain Detected from in Utero MRI

    PubMed Central

    Scott, Julia A.; Roosta, Ahmad; Rajagopalan, Vidya; Kim, Kio; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2012-01-01

    Early cortical folding and the emergence of structural brain asymmetries have been previously analyzed by neuropathology as well as qualitative analysis of magnetic resonance imaging (MRI) of fetuses and preterm neonates. In this study, we present a dedicated image analysis framework and its application for the detection of folding patterns during the critical period for the formation of many primary sulci (20–28 gestational weeks). Using structural information from in utero MRI, we perform morphometric analysis of cortical plate surface development and modeling of early folding in the normal fetal brain. First, we identify regions of the fetal brain surface that undergo significant folding changes during this developmental period and provide precise temporal staging of these changes for each region of interest. Then, we highlight the emergence of interhemispheric structural asymmetries that may be related to future functional specialization of cortical areas. Our findings complement previous descriptions of early sulcogenesis based on neuropathology and qualitative evaluation of 2D in utero MRI by accurate spatial and temporal mapping of the emergence of individual sulci as well as structural brain asymmetries. The study provides the missing starting point for their developmental trajectories and extends our understanding of normal cortical folding. PMID:21571694

  1. Early folding patterns and asymmetries of the normal human brain detected from in utero MRI.

    PubMed

    Habas, Piotr A; Scott, Julia A; Roosta, Ahmad; Rajagopalan, Vidya; Kim, Kio; Rousseau, Francois; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2012-01-01

    Early cortical folding and the emergence of structural brain asymmetries have been previously analyzed by neuropathology as well as qualitative analysis of magnetic resonance imaging (MRI) of fetuses and preterm neonates. In this study, we present a dedicated image analysis framework and its application for the detection of folding patterns during the critical period for the formation of many primary sulci (20-28 gestational weeks). Using structural information from in utero MRI, we perform morphometric analysis of cortical plate surface development and modeling of early folding in the normal fetal brain. First, we identify regions of the fetal brain surface that undergo significant folding changes during this developmental period and provide precise temporal staging of these changes for each region of interest. Then, we highlight the emergence of interhemispheric structural asymmetries that may be related to future functional specialization of cortical areas. Our findings complement previous descriptions of early sulcogenesis based on neuropathology and qualitative evaluation of 2D in utero MRI by accurate spatial and temporal mapping of the emergence of individual sulci as well as structural brain asymmetries. The study provides the missing starting point for their developmental trajectories and extends our understanding of normal cortical folding.

  2. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

    PubMed

    Smith, Carli J; Emge, Jacob R; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M; Sousa, Andrew J; Reardon, Colin; Sherman, Philip M; Barrett, Kim E; Gareau, Mélanie G

    2014-10-15

    The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis.

  3. Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Ma, Lijun

    2001-11-01

    A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

  4. Preservation of diffusion tensor properties during spatial normalization by use of tensor imaging and fibre tracking on a normal brain database.

    PubMed

    Müller, H-P; Unrath, A; Ludolph, A C; Kassubek, J

    2007-03-21

    White matter connectivity in the human brain can be mapped by diffusion tensor magnetic resonance imaging (DTI). After reconstruction, the diffusion tensors, the diffusion amplitude and the diffusion direction can be displayed on a morphological background. Consequently, diffusion tensor fibre tracking can be applied as a non-invasive in vivo technique for the delineation and quantification of specific white matter pathways. The aim of this study was to show that normalization to the Montreal Neurological Institute (MNI) stereotaxic standard space preserves specific diffusion features. Therefore, techniques for tensor imaging and fibre tracking were applied to the normalized brains as well as to the group averaged brain data. A normalization step of individual data was included by registration to a scanner- and sequence-specific DTI template data set which was created from a normal database transformed to MNI space. The algorithms were tested and validated for a group of 13 healthy controls.

  5. Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero

    PubMed Central

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A.; Kim, Kio; Corbett-Detig, James; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2011-01-01

    Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by MRI and ultrasound, which describe overall growth and provided mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20-28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the pre- and post-central gyri, right superior temporal gyrus and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human. PMID:21414909

  6. Periodontal disease associates with higher brain amyloid load in normal elderly.

    PubMed

    Kamer, Angela R; Pirraglia, Elizabeth; Tsui, Wai; Rusinek, Henry; Vallabhajosula, Shankar; Mosconi, Lisa; Yi, Li; McHugh, Pauline; Craig, Ronald G; Svetcov, Spencer; Linker, Ross; Shi, Chen; Glodzik, Lidia; Williams, Schantel; Corby, Patricia; Saxena, Deepak; de Leon, Mony J

    2015-02-01

    The accumulation of amyloid-β (Aβ) plaques is a central feature of Alzheimer's disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory and/or infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Thirty-eight cognitively normal, healthy, and community-residing elderly (mean age, 61 and 68% female) were examined in an Alzheimer's Disease Research Center and a University-Based Dental School. Linear regression models (adjusted for age, apolipoprotein E, and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using (11)C-Pittsburgh compound B (PIB) positron emission tomography imaging. After adjusting for confounders, clinical attachment loss (≥3 mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased PIB uptake in Aβ vulnerable brain regions (p = 0.002). We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with the previous animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations.

  7. Delineating Normal from Diseased Brain by Aminolevulinic Acid-Induced Fluorescence

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Stummer, Walter

    5-Aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX (PpIX) has been established as an orally applied drug to guide surgical resection of malignant brain tumors by exciting the red fluorescence of PpIX. The accumulation of PpIX in glioblastoma multiforme (GBM) is highly selective and provides excellent contrast to normal brain when using surgical microscopes with appropriately filtered light sources and cameras. The positive predictive value of fluorescent tissue is very high, enabling safe gross total resection of GBM and other brain tumors and improving prognosis of patients. Compared to other intraoperative techniques that have been developed with the aim of increasing the rate of safe gross total resections of malignant gliomas, PpIX fluorescence is considerably simpler, more cost effective, and comparably reliable. We present the basics of 5-ALA-based fluorescence-guided resection, and discuss the clinical results obtained for GBM and the experience with the fluorescence staining of other primary brain tumors and metastases as well as the results for spinal cord tumors. The phototoxicity of PpIX, increasingly used for photodynamic therapy of brain tumors, is mentioned briefly in this chapter.

  8. Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis.

    PubMed

    Ebihara, Chihiro; Ebihara, Ken; Aizawa-Abe, Megumi; Mashimo, Tomoji; Tomita, Tsutomu; Zhao, Mingming; Gumbilai, Valentino; Kusakabe, Toru; Yamamoto, Yuji; Aotani, Daisuke; Yamamoto-Kataoka, Sachiko; Sakai, Takeru; Hosoda, Kiminori; Serikawa, Tadao; Nakao, Kazuwa

    2015-08-01

    Seipin, encoded by BSCL2 gene, is a protein whose physiological functions remain unclear. Mutations of BSCL2 cause the most-severe form of congenital generalized lipodystrophy (CGL). BSCL2 mRNA is highly expressed in the brain and testis in addition to the adipose tissue in human, suggesting physiological roles of seipin in non-adipose tissues. Since we found BSCL2 mRNA expression pattern among organs in rat is similar to human while it is not highly expressed in mouse brain, we generated a Bscl2/seipin knockout (SKO) rat using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis. SKO rats showed total lack of white adipose tissues including mechanical fat such as bone marrow and retro-orbital fats, while physiologically functional brown adipose tissue was preserved. Besides the lipodystrophic phenotypes, SKO rats showed impairment of spatial working memory with brain weight reduction and infertility with azoospermia. We confirmed reduction of brain volume and number of sperm in human patients with BSCL2 mutation. This is the first report demonstrating that seipin is necessary for normal brain development and spermatogenesis in addition to white adipose tissue development.

  9. Periodontal disease associates with higher brain amyloid load in normal elderly

    PubMed Central

    Kamer, Angela R.; Pirraglia, Elizabeth; Tsui, Wai; Rusinek, Henry; Vallabhajosula, Shankar; Mosconi, Lisa; Yi, Li; McHugh, Pauline; Craig, Ronald G.; Svetcov, Spencer; Linker, Ross; Shi, Chen; Glodzik, Lidia; Williams, Schantel; Corby, Patricia; Saxena, Deepak; de Leon, Mony J.

    2015-01-01

    Background The accumulation of amyloid β plaques (Aβ) is a central feature of Alzheimer’s disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory/infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Methods Thirty-eight cognitively normal, healthy, community residing elderly (mean age 61; 68% female) were examined in an Alzheimer’s Disease research center and a University-based Dental School. Linear regression models (adjusted for age, ApoE and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using 11C-PIB PET imaging. Results After adjusting for confounders, clinical attachment loss (≥ 3mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased 11C-PIB uptake in Aβ vulnerable brain regions (p=0.002). Conclusion We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with prior animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations. PMID:25491073

  10. Alcohol Affects Brain Functional Connectivity and its Coupling with Behavior: Greater Effects in Male Heavy Drinkers

    PubMed Central

    Shokri-Kojori, Ehsan; Tomasi, Dardo; Wiers, Corinde E.; Wang, Gene-Jack; Volkow, Nora D.

    2016-01-01

    Acute and chronic alcohol exposure significantly affect behavior but the underlying neurobiological mechanisms are still poorly understood. Here we used functional connectivity density (FCD) mapping to study alcohol-related changes in resting brain activity and their association with behavior. Heavy drinkers (HD; N=16; 16 males) and normal controls (NM; N=24; 14 males) were tested after placebo and after acute alcohol administration. Group comparisons showed that NM had higher FCD in visual and prefrontal cortices, default-mode network regions, and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly increased FCD within the thalamus, impaired cognitive and motor functions, and affected self-reports of mood/drug effects in both groups. Partial least squares regression showed alcohol-induced changes in mood/drug effects were associated with changes in thalamic FCD in both groups. Disruptions in motor function were associated with increases in cerebellar FCD in NM and thalamus FCD in HD. Alcohol-induced declines in cognitive performance were associated with connectivity increases in visual cortex and thalamus in NM, but in HD, increases in precuneus FCD were associated with improved cognitive performance. Acute alcohol reduced “neurocognitive coupling”, the association between behavioral performance and FCD (indexing brain activity), an effect that was accentuated in HD compared to NM. Findings suggest that reduced cortical connectivity in HD contribute to decline in cognitive abilities associated with heavy alcohol consumption, whereas increased cerebellar connectivity in HD may have compensatory effects on behavioral performance. The results reveal how drinking history alters the association between brain functional connectivity density and individual differences in behavioral performance. PMID:27021821

  11. Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers.

    PubMed

    Shokri-Kojori, E; Tomasi, D; Wiers, C E; Wang, G-J; Volkow, N D

    2016-03-29

    Acute and chronic alcohol exposure significantly affect behavior but the underlying neurobiological mechanisms are still poorly understood. Here, we used functional connectivity density (FCD) mapping to study alcohol-related changes in resting brain activity and their association with behavior. Heavy drinkers (HD, N=16, 16 males) and normal controls (NM, N=24, 14 males) were tested after placebo and after acute alcohol administration. Group comparisons showed that NM had higher FCD in visual and prefrontal cortices, default mode network regions and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly increased FCD within the thalamus, impaired cognitive and motor functions, and affected self-reports of mood/drug effects in both groups. Partial least squares regression showed that alcohol-induced changes in mood/drug effects were associated with changes in thalamic FCD in both groups. Disruptions in motor function were associated with increases in cerebellar FCD in NM and thalamus FCD in HD. Alcohol-induced declines in cognitive performance were associated with connectivity increases in visual cortex and thalamus in NM, but in HD, increases in precuneus FCD were associated with improved cognitive performance. Acute alcohol reduced 'neurocognitive coupling', the association between behavioral performance and FCD (indexing brain activity), an effect that was accentuated in HD compared with NM. Findings suggest that reduced cortical connectivity in HD contribute to decline in cognitive abilities associated with heavy alcohol consumption, whereas increased cerebellar connectivity in HD may have compensatory effects on behavioral performance. The results reveal how drinking history alters the association between brain FCD and individual differences in behavioral performance.Molecular Psychiatry advance online publication, 29 March 2016; doi:10.1038/mp.2016.25.

  12. Brain size affects female but not male survival under predation threat

    PubMed Central

    Kotrschal, Alexander; Buechel, Séverine D; Zala, Sarah M; Corral-Lopez, Alberto; Penn, Dustin J; Kolm, Niclas; Sorci, Gabriele

    2015-01-01

    There is remarkable diversity in brain size among vertebrates, but surprisingly little is known about how ecological species interactions impact the evolution of brain size. Using guppies, artificially selected for large and small brains, we determined how brain size affects survival under predation threat in a naturalistic environment. We cohoused mixed groups of small- and large-brained individuals in six semi-natural streams with their natural predator, the pike cichlid, and monitored survival in weekly censuses over 5 months. We found that large-brained females had 13.5% higher survival compared to small-brained females, whereas the brain size had no discernible effect on male survival. We suggest that large-brained females have a cognitive advantage that allows them to better evade predation, whereas large-brained males are more colourful, which may counteract any potential benefits of brain size. Our study provides the first experimental evidence that trophic interactions can affect the evolution of brain size. PMID:25960088

  13. Physical Activity Affects Brain Integrity in HIV + Individuals

    PubMed Central

    Ortega, Mario; Baker, Laurie M.; Vaida, Florin; Paul, Robert; Basco, Brian; Ances, Beau M.

    2015-01-01

    Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV−) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV +) individuals. Seventy HIV + individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV + individuals were classified as physically active (any energy expended above resting expenditure, n = 22) or sedentary (n = 48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV + individuals had similar demographic and laboratory values, but the active group had higher education (14.0 vs. 12.6 years, p = .034). Physically active HIV + individuals performed better on executive (p = .040, unadjusted; p = .043, adjusted) but not motor function (p = .17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson’s r = 0.45, p = 0.035) but not motor (r = 0.21; p = .35) performance. In adjusted analyses the physically active HIV + individuals had larger putamen volumes (p = .019). A positive relationship exists between PA and brain integrity in HIV + individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV + individuals. PMID:26581799

  14. Haemopexin affects iron distribution and ferritin expression in mouse brain

    PubMed Central

    Morello, Noemi; Tonoli, Elisabetta; Logrand, Federica; Fiorito, Veronica; Fagoonee, Sharmila; Turco, Emilia; Silengo, Lorenzo; Vercelli, Alessandro; Altruda, Fiorella; Tolosano, Emanuela

    2009-01-01

    Haemopexin (Hx) is an acute phase plasma glycoprotein, mainly produced by the liver and released into plasma where it binds heme with high affinity and delivers it to the liver. This system provides protection against free heme-mediated oxidative stress, limits access by pathogens to heme and contributes to iron homeostasis by recycling heme iron. Hx protein has been found in the sciatic nerve, skeletal muscle, retina, brain and cerebrospinal fluid (CSF). Recently, a comparative proteomic analysis has shown an increase of Hx in CSF from patients with Alzheimer’s disease, thus suggesting its involvement in heme detoxification in brain. Here, we report that Hx is synthesised in brain by the ventricular ependymal cells. To verify whether Hx is involved in heme scavenging in brain, and consequently, in the control of iron level, iron deposits and ferritin expression were analysed in cerebral regions known for iron accumulation. We show a twofold increase in the number of iron-loaded oligodendrocytes in the basal ganglia and thalamus of Hx-null mice compared to wild-type controls. Interestingly, there was no increase in H- and L-ferritin expression in these regions. This condition is common to several human neurological disorders such as Alzheimer’s disease and Parkinson’s disease in which iron loading is not associated with an adequate increase in ferritin expression. However, a strong reduction in the number of ferritin-positive cells was observed in the cerebral cortex of Hx-null animals. Consistent with increased iron deposits and inadequate ferritin expression, malondialdehyde level and Cu–Zn superoxide dismutase-1 expression were higher in the brain of Hx-null mice than in that of wild-type controls. These data demonstrate that Hx plays an important role in controlling iron distribution within brain, thus suggesting its involvement in iron-related neurodegenerative diseases. PMID:19120692

  15. Default, Cognitive, and Affective Brain Networks in Human Tinnitus

    DTIC Science & Technology

    2014-10-01

    fMRI session 1 in which subjects perform a working memory task (“2-Back”) and a simple detection task (“Detect 1’s”) based on (a) visual and (b...two major brain networks: the cognitive control network (CCN) and the default mode network (DMN). Using fMRI , we are examining brain activation in...subjects performing cognitive tasks that engage the CCN and DMN. One task is heavily reliant on working memory (N-back) and the other on selective

  16. The whole-brain N-acetylaspartate correlates with education in normal adults.

    PubMed

    Glodzik, Lidia; Wu, William E; Babb, James S; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U; Gass, Achim; Gonen, Oded

    2012-10-30

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis, 97 middle aged to elderly subjects (51-89 years old, 38% women) underwent brain magnetic resonance imaging and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount by the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject's educational attainment was the sum of his/her years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51-70 years old) participants. In this group, education explained 21% of the variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristics predisposing a subject to higher achievements later in life. We propose that late-life WBNAA may be more affected by other factors acting at midlife and later.

  17. IGF-I redirects doublecortin-positive cell migration in the normal adult rat brain.

    PubMed

    Maucksch, C; McGregor, A L; Yang, M; Gordon, R J; Yang, M; Connor, B

    2013-06-25

    The migration of subventricular zone (SVZ)-derived neural precursor cells through the rostral migratory stream (RMS) to the olfactory bulb is tightly regulated by local micro-environmental cues. Insulin-like Growth Factor-I (IGF-I) can stimulate the migration of several neuronal cell types and acts as a 'departure' factor in the avian SVZ. To establish whether IGF-I can also act as a migratory factor for adult neuronal precursor cells in vivo, in addition to its well established role in precursor cell proliferation and differentiation, we used AAV2-mediated gene transfer to produce ectopic expression of IGF-I in the normal adult rat striatum. We then assessed whether the expression of IGF-I would recruit SVZ-derived neuronal precursor cells from the RMS into the striatum. Ectopic expression of IGF-I in the normal adult rat brain significantly increased the number of doublecortin (Dcx)-positive cells and the extent of their migration into the striatum 4 and 8 weeks after AAV2-IGF-I injection but did not promote neuronal differentiation. In vitro migration assays confirmed that IGF-I is an inducer of migration and directs SVZ-derived adult neuronal precursor cell migration by both chemotaxis and chemokinesis. These results demonstrate that overexpression of IGF-I in the normal adult rat brain can override the normal cues directing precursor cell migration along the RMS and can redirect precursor cell migration into a non-neurogenic region. Enhanced expression of IGF-I following brain injury may therefore act as a diffusible factor mediating precursor cell migration to areas of neuronal cell damage.

  18. Testosterone affects language areas of the adult human brain

    PubMed Central

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

    2016-01-01

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

  19. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  20. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  1. Testosterone affects language areas of the adult human brain.

    PubMed

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

    2016-05-01

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

  2. Default, Cognitive, and Affective Brain Networks in Human Tinnitus

    DTIC Science & Technology

    2015-10-01

    Mapping (SPM8; a freely available fMRI analysis package), fMRI and structural imaging data from each session were aligned to a standard brain atlas...maps are superimposed on a mean of structural scans (average over subjects contributing to the activation maps). 3.3 Implication of results for the

  3. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    PubMed

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  4. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

    NASA Technical Reports Server (NTRS)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  5. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    SciTech Connect

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-06-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.

  6. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease

    PubMed Central

    Rosario, Emily R.; Chang, Lilly; Head, Elizabeth H.; Stanczyk, Frank Z.; Pike, Christian J.

    2009-01-01

    We examined the relationships between normal aging, Alzheimer’s disease (AD), and brain levels of sex steroid hormones in men and women. In postmortem brain tissue from neuropathologically normal, postmenopausal women, we found no age-related changes in brain levels of either androgens or estrogens. In comparing women with and without AD at different ages, brain levels of estrogens and androgens were lower in AD cases aged 80 years and older but not significantly different in the 60–79 year age range. In male brains, we observed that normal aging was associated with significant decreases in androgens but not estrogens. Further, in men aged 60–79 years, brain levels of testosterone but not estrogens were lower in cases with mild neuropathological changes as well as those with advanced AD neuropathology. In male cases over age 80, brain levels hormones did not significantly vary by neuropathological status. To begin investigating the relationships between hormone levels and indices of AD neuropathology, we measured brain levels of soluble β-amyloid (Aβ). In male cases with mild neuropathological changes, we found an inverse relationship between brain levels of testosterone and soluble Aβ. Collectively, these findings demonstrate sex-specific relationships between normal, age-related depletion of androgens and estrogens in men and women, which may be relevant to development of AD. PMID:19428144

  7. Free magnesium levels in normal human brain and brain tumors: sup 31 P chemical-shift imaging measurements at 1. 5 T

    SciTech Connect

    Taylor, J.S.; Vigneron, D.B.; Murphy-Boesch, J.; Nelson, S.J.; Kessler, H.B.; Coia, L.; Curran, W.; Brown, T.R. )

    1991-08-01

    The authors have studied a series of normal subjects and patients with brain tumors, by using {sup 31}P three-dimensional chemical shift imaging to obtain localized {sup 31}P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg{sup 2+}, as indicated by the chemical shift {delta} of the {beta}-P resonance of ATP. The ATP {beta}P resonance position in brain thus is sensitive to changes in intracellular free Mg{sup 2+} concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the {delta} vs. Mg{sup 2+} titration curve for ATP. They have measured the ATP {beta}-P shift and compared intracellular free Mg{sup 2+} concentration and fractions of free ATP for normal individuals and a limited series of patients with brain tumors. In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg{sup 2+} was increased, and the fraction of free ATP was decreased, compared with normal brain.

  8. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    PubMed

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  9. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection.

  10. Does epidural analgesia affect the rate of spontaneous obstetric lacerations in normal births?

    PubMed

    Albers, Leah L; Migliaccio, Laura; Bedrick, Edward J; Teaf, Dusty; Peralta, Patricia

    2007-01-01

    The precise relationship between epidural use and genital tract lacerations in normal childbirth is unclear. Data from a clinical trial on measures to lower genital tract trauma in vaginal birth were used for a secondary analysis. The goal was to assess whether epidurals affect the rate of spontaneous obstetric lacerations in normal vaginal births. Maternal characteristics and intrapartum variables were compared in women who did and did not use an epidural in labor, and also in those with and without any sutured lacerations following vaginal birth. Variables that were statistically different in both cases were entered into regression equations for simultaneous adjustment. Epidural use was not an independent predictor of sutured lacerations. Predictors of sutured lacerations included nulliparity, a prolonged second stage, being non-Hispanic white, and an infant birthweight greater than 4000 grams. Elements of midwifery management need further research.

  11. NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION

    PubMed Central

    Emblem, Kyrre; Pinho, Marco; Chandra, Vyshak; Gerstner, Elizabeth; Stufflebeam, Steve; Sorenson, Greg; Harris, Gordon; Freedman, Rachel; Sohl, Jessica; Younger, Jerry; Krop, Ian; Winer, Eric; Lin, Nancy

    2014-01-01

    INTRODUCTION: As systemic therapy improves, brain metastases are increasingly common in patients with breast cancer. Unfortunately, effective therapy with durable control has remained elusive [1]. Combining bevacizumab and cyototoxic chemotherapy is an appealing approach as the anti-angiogenic effect of bevicizumab may improve delivery of cytotoxic drugs to brain tumors. METHODS: We conducted a Phase II study of patients with parenchymal brain metastasis treated with bevacizumab and carboplatin [2]. Patients could have any hormone receptor status or any number of prior therapies. Patients with HER2+ breast cancer also received trastuzamab. Correlative perfusion MRI scans to look at tumor perfusion, blood volume, vessel calibers and relative oxygen saturation (ΔSO2) levels were performed at baseline, day 1, and after 2 months of therapy [3, 4]. For consistency, the largest contrast-enhancing lesion in each patient visible on all three MR visits was selected for analysis. RESULTS: Thirty-eight patients were enrolled in the study of which 32 had, paired evaluable imaging datasets. Compared to baseline, 12/32 patients were identified as responders by a durable increase in ΔSO2 levels at day 1 and at 2 months above a 5% measurement error threshold. The remaining patients were identified by stable (15/32) or reduced (5/32) ΔSO2 levels. Patients responding to therapy showed increased tumor perfusion (Mann-Whitney; P<0.01) and prolonged survival (625 versus 400 days, Cox regression; P<0.05) Fig. 1B). A collective and selective pruning of macroscopic tumor vessels (>10 µm) were seen across all patients. CONCLUSIONS: Similar to primary brain tumors [2, 3], perfusion MRI demonstrates that anti-angiogenic therapy can induce vascular normalization in a subset of patients with metastatic breast cancer to the brain. Our data indicate that the vascular response may also be associated with improved survival. [1] Lin NU, Lancet Oncol 2013 [2] Sorensen AG, Cancer Res 2012 [3

  12. Clinical NMR imaging of the brain in children: normal and neurologic disease

    SciTech Connect

    Johnson, M.A,; Pennock, J.M.; Bydder, G.M.; Steiner, R.E.; Thomas, D.J.; Hayward, R.; Bryant, D.R.T.; Payne, J.A.; Levene, M.I.; Whitelaw, A.; Dubowitz, L.M.S.; Dubowitz, V.

    1983-11-01

    The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified by virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.

  13. Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior.

    PubMed

    Vigers, A J; Amin, D S; Talley-Farnham, T; Gorski, J A; Xu, B; Jones, K R

    2012-06-14

    Brain-derived neurotrophic factor (BDNF) plays important roles in the development, maintenance, and plasticity of the mammalian forebrain. These functions include regulation of neuronal maturation and survival, axonal and dendritic arborization, synaptic efficacy, and modulation of complex behaviors including depression and spatial learning. Although analysis of mutant mice has helped establish essential developmental functions for BDNF, its requirement in the adult is less well documented. We have studied late-onset forebrain-specific BDNF knockout (CaMK-BDNF(KO)) mice, in which BDNF is lost primarily from the cortex and hippocampus in early adulthood, well after BDNF expression has begun in these structures. We found that although CaMK-BDNF(KO) mice grew at a normal rate and can survive more than a year, they had smaller brains than wild-type siblings. The CaMK-BDNF(KO) mice had generally normal behavior in tests for ataxia and anxiety, but displayed reduced spatial learning ability in the Morris water task and increased depression in the Porsolt swim test. These behavioral deficits were very similar to those we previously described in an early-onset forebrain-specific BDNF knockout. To identify an anatomical correlate of the abnormal behavior, we quantified dendritic spines in cortical neurons. The spine density of CaMK-BDNF(KO) mice was normal at P35, but by P84, there was a 30% reduction in spine density. The strong similarities we find between early- and late-onset BDNF knockouts suggest that BDNF signaling is required continuously in the CNS for the maintenance of some forebrain circuitry also affected by developmental BDNF depletion.

  14. Tasting calories differentially affects brain activation during hunger and satiety.

    PubMed

    van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

    2015-02-15

    An important function of eating is ingesting energy. Our objectives were to assess whether oral exposure to caloric and non-caloric stimuli elicits discriminable responses in the brain and to determine in how far these responses are modulated by hunger state and sweetness. Thirty women tasted three stimuli in two motivational states (hunger and satiety) while their brain responses were measured using functional magnetic resonance imaging in a randomized crossover design. Stimuli were solutions of sucralose (sweet, no energy), maltodextrin (non-sweet, energy) and sucralose+maltodextrin (sweet, energy). We found no main effect of energy content and no interaction between energy content and sweetness. However, there was an interaction between hunger state and energy content in the median cingulate (bilaterally), ventrolateral prefrontal cortex, anterior insula and thalamus. This indicates that the anterior insula and thalamus, areas in which hunger state and taste of a stimulus are integrated, also integrate hunger state with caloric content of a taste stimulus. Furthermore, in the median cingulate and ventrolateral prefrontal cortex, tasting energy resulted in more activation during satiety compared to hunger. This finding indicates that these areas, which are known to be involved in processes that require approach and avoidance, are also involved in guiding ingestive behavior. In conclusion, our results suggest that energy sensing is a hunger state dependent process, in which the median cingulate, ventrolateral prefrontal cortex, anterior insula and thalamus play a central role by integrating hunger state with stimulus relevance.

  15. Voxel-based Morphometry of Brain MRI in Normal Aging and Alzheimer's Disease.

    PubMed

    Matsuda, Hiroshi

    2013-02-01

    Voxel-based morphometry (VBM) using structural brain MRI has been widely used for assessment of normal aging and Alzheimer's disease (AD). VBM of MRI data comprises segmentation into gray matter, white matter, and cerebrospinal fluid partitions, anatomical standardization of all the images to the same stereotactic space using linear affine transformation and further non-linear warping, smoothing, and finally performing a statistical analysis. Two techniques for VBM are commonly used, optimized VBM using statistical parametric mapping (SPM) 2 or SPM5 with non-linear warping based on discrete cosine transforms and SPM8 plus non-linear warping based on diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL). In normal aging, most cortical regions prominently in frontal and insular areas have been reported to show age-related gray matter atrophy. In contrast, specific structures such as amygdala, hippocampus, and thalamus have been reported to be preserved in normal aging. On the other hand, VBM studies have demonstrated progression of atrophy mapping upstream to Braak's stages of neurofibrillary tangle deposition in AD. The earliest atrophy takes place in medial temporal structures. Stand-alone VBM software using SPM8 plus DARTEL running on Windows has been newly developed as an adjunct to the clinical assessment of AD. This software provides a Z-score map as a consequence of comparison of a patient's MRI with a normal database.

  16. Effects of active music therapy on the normal brain: fMRI based evidence.

    PubMed

    Raglio, Alfredo; Galandra, Caterina; Sibilla, Luisella; Esposito, Fabrizio; Gaeta, Francesca; Di Salle, Francesco; Moro, Luca; Carne, Irene; Bastianello, Stefano; Baldi, Maurizia; Imbriani, Marcello

    2016-03-01

    The aim of this study was to investigate the neurophysiological bases of Active Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed, healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT sessions based on the free sonorous-music improvisation using rhythmic and melodic instruments. After these sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased array head coil was used, and the image analysis was performed with Brain Voyager QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle temporal gyrus and right superior temporal sulcus, (2) the right middle frontal gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus, (4) the left superior temporal sulcus and (5) the left middle temporal gyrus. These results are consistent with the psychological bases of the AMT approach and with the activation of brain areas involved in memory and autobiographical processes, and also in personal or interpersonal significant experiences. Further studies are required to confirm these findings and to explain possible effects of AMT in clinical settings.

  17. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    PubMed Central

    Kennard, John A.; Woodruff-Pak, Diana S.

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena. PMID:21647305

  18. Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

    PubMed

    Does, Mark D; Parsons, Edward C; Gore, John C

    2003-02-01

    Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter.

  19. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease

    PubMed Central

    Lipinski, Marta M.; Zheng, Bin; Lu, Tao; Yan, Zhenyu; Py, Bénédicte F.; Ng, Aylwin; Xavier, Ramnik J.; Li, Cheng; Yankner, Bruce A.; Scherzer, Clemens R.; Yuan, Junying

    2010-01-01

    Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation of misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to the autophagy dysfunction are still not clear. Based on the results of a genome-wide screen, we show that reactive oxygen species (ROS) serve as common mediators upstream of the activation of the type III PI3 kinase, which is critical for the initiation of autophagy. Furthermore, ROS play an essential function in the induction of the type III PI3 kinase and autophagy in response to amyloid β peptide, the main pathogenic mediator of Alzheimer's disease (AD). However, lysosomal blockage also caused by Aβ is independent of ROS. In addition, we demonstrate that autophagy is transcriptionally down-regulated during normal aging in the human brain. Strikingly, in contrast to normal aging, we observe transcriptional up-regulation of autophagy in the brains of AD patients, suggesting that there might be a compensatory regulation of autophagy. Interestingly, we show that an AD drug and an AD drug candidate have inhibitory effects on autophagy, raising the possibility that decreasing input into the lysosomal system may help to reduce cellular stress in AD. Finally, we provide a list of candidate drug targets that can be used to safely modulate levels of autophagy without causing cell death. PMID:20660724

  20. Brain perfusion SPECT in the mouse: normal pattern according to gender and age.

    PubMed

    Apostolova, Ivayla; Wunder, Andreas; Dirnagl, Ulrich; Michel, Roger; Stemmer, Nina; Lukas, Mathias; Derlin, Thorsten; Gregor-Mamoudou, Betina; Goldschmidt, Jürgen; Brenner, Winfried; Buchert, Ralph

    2012-12-01

    Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal activity and a parameter of primary interest in the diagnosis of many diseases. The increasing use of mouse models spawns the demand for in vivo measurement of rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at adequate sensitivity and is therefore a promising tool for imaging the mouse brain. This study evaluates the feasibility of mouse brain perfusion SPECT and assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were performed in 18 juvenile mice aged 7.5 ± 1.5weeks, and in the same animals at young adulthood, 19.1 ± 4.0 weeks (nanoSPECT/CTplus, general purpose mouse apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. For testing lateral asymmetry, each SPECT was left-right flipped prior to stereotactical normalization. Flipped and unflipped SPECTs were compared by paired testing. Peak brain uptake was similar for ECD and HMPAO: 1.8 ± 0.2 and 2.1 ± 0.6 %ID (p=0.357). Washout after the peak was much faster for ECD than for HMPAO: 24 ± 7min vs. 4.6 ± 1.7h (p=0.001). The general linear model for repeated measures with gender as an intersubject factor revealed an increase in relative HMPAO uptake with age in the neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left hemisphere, was detected primarily in the neocortex, both at juvenile age (asymmetry index AI=2.7 ± 1

  1. Brain network analysis reveals affected connectome structure in bipolar I disorder.

    PubMed

    Collin, Guusje; van den Heuvel, Martijn P; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A; Kahn, René S

    2016-01-01

    The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P < 0.001) to reduced connectivity strength of interhemispheric connections (-13.0%, P = 0.001). Bipolar disorder patients were found not to show predominant alterations in the strength of brain hub connections in general, or of connections spanning brain hubs (i.e., "rich club" connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected.

  2. Assembly and deacetylation of N-acetylglucosaminyl-plasmanylinositol in normal and affected paroxysmal nocturnal hemoglobinuria cells

    SciTech Connect

    Hirose, Shinichi; Ravi, Lakshmeswari; Medof, M.D. ); Hazra, S.V. )

    1991-05-01

    Decay-accelerating factor (DAF) is anchored in cell membranes by a glycosyl-plasmanylinositol (GPI) moiety that is transferred to it en bloc in the rough endoplasmic reticulum. To analyze the biochemical reactions involved in preassembly of this structure, a human hematopoietic cell-free system was employed. Incubation of cell extracts with UDP-({sup 3}H)GlcNAc and butanol partitioning of reaction mixtures yielded two products similar in TLC mobility to intermediates described in Trypanoxoma brucei. Both species were sensitive to Bacillus thuringiensis phosphatidylinositol-specific phospholipase C, indicative of association of ({sup 3}H)GlcNAc label with a plasmanylinositol-containing acceptor. Kinetic and pulse-chase experiments indicated that the slower-migrating species was a product of the faster and that it, but not the faster, was sensitive to both GPI-specific phospholipase D and nitrous acid deamination, consistent with conversion of GlcNAc- to GlcN-plasmanylinositol. Lysates of normal and of affected blood leukocytes from two paroxysmal nocturnal hemoglobinuria (PNH) patients supported assembly of the two intermediates within 1 min. Thus, the initial enzymes mediating human GPI-anchor assembly are GlcNAc-plasmanylinositol transferase and GlcNAc-plasmanylinositol deacetylase, their substrates contain plasmanylinositols, and the products of their activities are normal in affected PNH cells.

  3. Cdk4 deficiency inhibits skin tumor development but does not affect normal keratinocyte proliferation.

    PubMed

    Rodriguez-Puebla, Marcelo L; Miliani de Marval, Paula L; LaCava, Margaret; Moons, David S; Kiyokawa, Hiroaki; Conti, Claudio J

    2002-08-01

    Most human tumors have mutations that result in deregulation of the cdk4/cyclin-Ink4-Rb pathway. Overexpression of D-type cyclins or cdk4 and inactivation of Ink4 inhibitors are common in human tumors. Conversely, lack of cyclin D1 expression results in significant reduction in mouse skin and mammary tumor development. However, complete elimination of tumor development was not observed in these models, suggesting that other cyclin/cdk complexes play an important role in tumorigenesis. Here we described the effects of cdk4 deficiency on mouse skin proliferation and tumor development. Cdk4 deficiency resulted in a 98% reduction in the number of tumors generated through the two-stage carcinogenesis model. The absence of cdk4 did not affect normal keratinocyte proliferation and both wild-type and cdk4 knockout epidermis are equally affected after topical treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in epidermal hyperplasia. In similar fashion, cdk4 knockout keratinocytes proliferated well in an in vivo model of wound-induced proliferation. Biochemical studies in mouse epidermis showed that cdk6 activity increased twofold in cdk4-deficient mice compared to wild-type siblings. These results suggest that therapeutic approaches to inhibit cdk4 activity could provide a target to inhibit tumor development with minimal or no effect in normal tissue.

  4. Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

    PubMed

    Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

    2017-02-01

    Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

  5. Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease.

    PubMed

    Mosch, Birgit; Morawski, Markus; Mittag, Anja; Lenz, Dominik; Tarnok, Attila; Arendt, Thomas

    2007-06-27

    Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease (AD). A more than diploid DNA content in differentiated neurons might alternatively result from chromosome mis-segregation during mitosis in neuronal progenitor cells. It was our objective to distinguish between these two mechanisms for aneuploidy and to provide evidence for a functional cell cycle in AD. Using slide-based cytometry, chromogenic in situ hybridization, and PCR amplification of alu-repeats, we quantified the DNA amount of identified cortical neurons in normal human brain and AD and analyzed the link between a tetraploid DNA content and expression of the early mitotic marker cyclin B1. In the normal brain, the number of neurons with a more than diploid content amounts to approximately 10%. Less than 1% of neurons contains a tetraploid DNA content. These neurons do not express cyclin B1, most likely representing constitutional tetraploidy. This population of cyclin B1-negative tetraploid neurons, at a reduced number, is also present in AD. In addition, a population of cyclin B1-positive tetraploid neurons of approximately 2% of all neurons was observed in AD. Our results indicate that at least two different mechanisms need to be distinguished giving rise to a tetraploid DNA content in the adult brain. Constitutional aneuploidy in differentiated neurons might be more frequent than previously thought. It is, however, not elevated in AD. In addition, in AD some neurons have re-entered the cell cycle and entirely passed through a functional interphase with a complete DNA replication.

  6. Expression of the human ETS-2 oncogene in normal fetal tissues and in the brain of a fetus with trisomy 21.

    PubMed

    Baffico, M; Perroni, L; Rasore-Quartino, A; Scartezzini, P

    1989-10-01

    The expression of the ETS-2 proto-oncogene, located on chromosome 21, in normal fetal tissues and in neural tissue of a fetus affected by Down syndrome has been investigated. The results show that the ETS-2 proto-oncogene is expressed in almost all the tissues examined and that it is transcribed at constant levels in neural tissue between the 13th and 24th weeks. ETS-2 expression appeared to be slightly increased in Down syndrome brain compared with that of normal controls of the same gestational age.

  7. BDNF-estrogen interactions in hippocampal mossy fiber pathway: implications for normal brain function and disease

    PubMed Central

    Harte-Hargrove, Lauren; MacLusky, Neil J.; Scharfman, Helen E.

    2013-01-01

    The neurotrophin BDNF and the steroid hormone estrogen exhibit potent effects on hippocampal neurons during development and in adulthood. BDNF and estrogen have also been implicated in the etiology of diverse types of neurological disorders or psychiatric illnesses, or have been discussed as potentially important in treatment. Although both are typically studied independently, it has been suggested that BDNF mediates several of the effects of estrogen in hippocampus, and that these interactions play a role in the normal brain as well as disease. Here we focus on the mossy fiber (MF) pathway of the hippocampus, a critical pathway in normal hippocampal function, and a prime example of a location where numerous studies support an interaction between BDNF and estrogen in the rodent brain. We first review the temporal and spatially-regulated expression of BDNF and estrogen in the MFs, as well as their receptors. Then we consider the results of studies that suggest that 17β-estradiol alters hippocampal function by its influence on BDNF expression in the MF pathway. We also address the hypothesis that estrogen influences hippocampus by mechanisms related not only to the mature form of BDNF, acting at trkB receptors, but also by regulating the precursor, proBDNF, acting at p75NTR. We suggest that the interactions between BDNF and 17β-estradiol in the MFs are potentially important in the normal function of the hippocampus, and have implications for sex differences in functions that depend on the MFs and in diseases where MF plasticity has been suggested to play an important role, Alzheimer’s disease, epilepsy and addiction. PMID:23276673

  8. [Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury: a study by the positron emission tomography in twenty subjects with normal MRI findings].

    PubMed

    Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka

    2002-06-01

    Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerbral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with 15O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO2 in all regions. Then we compared rCBF, OEF, and CMRO2 between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO2 along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO2 of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of "relative luxury perfusion". Comparison of rCBF, OEF and CMRO2 between normal group and impaired group revealed that CMRO2 of the impaired group was significantly lower than that of the normal group in the bilateral frontal, temporal, and occipital lobe. After

  9. Tracheal decannulation protocol in patients affected by traumatic brain injury.

    PubMed

    Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

    2014-04-01

    Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing.

  10. Brain systems for assessing the affective value of faces

    PubMed Central

    Said, Christopher P.; Haxby, James V.; Todorov, Alexander

    2011-01-01

    Cognitive neuroscience research on facial expression recognition and face evaluation has proliferated over the past 15 years. Nevertheless, large questions remain unanswered. In this overview, we discuss the current understanding in the field, and describe what is known and what remains unknown. In §2, we describe three types of behavioural evidence that the perception of traits in neutral faces is related to the perception of facial expressions, and may rely on the same mechanisms. In §3, we discuss cortical systems for the perception of facial expressions, and argue for a partial segregation of function in the superior temporal sulcus and the fusiform gyrus. In §4, we describe the current understanding of how the brain responds to emotionally neutral faces. To resolve some of the inconsistencies in the literature, we perform a large group analysis across three different studies, and argue that one parsimonious explanation of prior findings is that faces are coded in terms of their typicality. In §5, we discuss how these two lines of research—perception of emotional expressions and face evaluation—could be integrated into a common, cognitive neuroscience framework. PMID:21536552

  11. Tracheal Decannulation Protocol in Patients Affected by Traumatic Brain Injury

    PubMed Central

    Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

    2014-01-01

    Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing. PMID:25992074

  12. [Quantitative analysis method based on fractal theory for medical imaging of normal brain development in infants].

    PubMed

    Li, Heheng; Luo, Liangping; Huang, Li

    2011-02-01

    The present paper is aimed to study the fractal spectrum of the cerebral computerized tomography in 158 normal infants of different age groups, based on the calculation of chaotic theory. The distribution range of neonatal period was 1.88-1.90 (mean = 1.8913 +/- 0.0064); It reached a stable condition at the level of 1.89-1.90 during 1-12 months old (mean = 1.8927 +/- 0.0045); The normal range of 1-2 years old infants was 1.86-1.90 (mean = 1.8863 +/- 4 0.0085); It kept the invariance of the quantitative value among 1.88-1.91(mean = 1.8958 +/- 0.0083) during 2-3 years of age. ANOVA indicated there's no significant difference between boys and girls (F = 0.243, P > 0.05), but the difference of age groups was significant (F = 8.947, P < 0.001). The fractal dimension of cerebral computerized tomography in normal infants computed by box methods was maintained at an efficient stability from 1.86 to 1.91. It indicated that there exit some attractor modes in pediatric brain development.

  13. From homogeneous to fractal normal and tumorous microvascular networks in the brain.

    PubMed

    Risser, Laurent; Plouraboué, Franck; Steyer, Alexandre; Cloetens, Peter; Le Duc, Géraldine; Fonta, Caroline

    2007-02-01

    We studied normal and tumorous three-dimensional (3D) microvascular networks in primate and rat brain. Tissues were prepared following a new preparation technique intended for high-resolution synchrotron tomography of microvascular networks. The resulting 3D images with a spatial resolution of less than the minimum capillary diameter permit a complete description of the entire vascular network for volumes as large as tens of cubic millimeters. The structural properties of the vascular networks were investigated by several multiscale methods such as fractal and power-spectrum analysis. These investigations gave a new coherent picture of normal and pathological complex vascular structures. They showed that normal cortical vascular networks have scale-invariant fractal properties on a small scale from 1.4 mum up to 40 to 65 mum. Above this threshold, vascular networks can be considered as homogeneous. Tumor vascular networks show similar characteristics, but the validity range of the fractal regime extend to much larger spatial dimensions. These 3D results shed new light on previous two dimensional analyses giving for the first time a direct measurement of vascular modules associated with vessel-tissue surface exchange.

  14. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain.

    PubMed

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-11-13

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies.

  15. Normal adult aging and the contextual influences affecting speech and meaningful sound perception.

    PubMed

    Aydelott, Jennifer; Leech, Robert; Crinion, Jennifer

    2010-12-01

    It is widely accepted that hearing loss increases markedly with age, beginning in the fourth decade ISO 7029 (2000). Age-related hearing loss is typified by high-frequency threshold elevation and associated reductions in speech perception because speech sounds, especially consonants, become inaudible. Nevertheless, older adults often report additional and progressive difficulties in the perception and comprehension of speech, often highlighted in adverse listening conditions that exceed those reported by younger adults with a similar degree of high-frequency hearing loss (Dubno, Dirks, & Morgan) leading to communication difficulties and social isolation (Weinstein & Ventry). Some of the age-related decline in speech perception can be accounted for by peripheral sensory problems but cognitive aging can also be a contributing factor. In this article, we review findings from the psycholinguistic literature predominantly over the last four years and present a pilot study illustrating how normal age-related changes in cognition and the linguistic context can influence speech-processing difficulties in older adults. For significant progress in understanding and improving the auditory performance of aging listeners to be made, we discuss how future research will have to be much more specific not only about which interactions between auditory and cognitive abilities are critical but also how they are modulated in the brain.

  16. Normal Adult Aging and the Contextual Influences Affecting Speech and Meaningful Sound Perception

    PubMed Central

    Aydelott, Jennifer; Leech, Robert; Crinion, Jennifer

    2010-01-01

    It is widely accepted that hearing loss increases markedly with age, beginning in the fourth decade ISO 7029 (2000). Age-related hearing loss is typified by high-frequency threshold elevation and associated reductions in speech perception because speech sounds, especially consonants, become inaudible. Nevertheless, older adults often report additional and progressive difficulties in the perception and comprehension of speech, often highlighted in adverse listening conditions that exceed those reported by younger adults with a similar degree of high-frequency hearing loss (Dubno, Dirks, & Morgan) leading to communication difficulties and social isolation (Weinstein & Ventry). Some of the age-related decline in speech perception can be accounted for by peripheral sensory problems but cognitive aging can also be a contributing factor. In this article, we review findings from the psycholinguistic literature predominantly over the last four years and present a pilot study illustrating how normal age-related changes in cognition and the linguistic context can influence speech-processing difficulties in older adults. For significant progress in understanding and improving the auditory performance of aging listeners to be made, we discuss how future research will have to be much more specific not only about which interactions between auditory and cognitive abilities are critical but also how they are modulated in the brain. PMID:21307006

  17. Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice

    SciTech Connect

    Bendotti, C.; Forloni, G.L.; Morgan, R.A.; O'Hara, B.F.; Oster-Granite, M.L.; Reeves, R.H.; Gearhart, J.D.; Coyle, J.T. )

    1988-05-01

    Amyloid precursor protein mRNA was localized in frozen sections from normal and experimentally lesioned adult mouse brain and from normal and aneuploid fetal mouse brain by in situ hybridization with a {sup 35}S-labeled mouse cDNA probe. The highest levels of hybridization in adult brain were associated with neurons, primarily in telencephalic structures. The dense labeling associated with hippocampal pyramidal cells was reduced significantly when the cells were eliminated by injection of the neurotoxin ibotenic acid but was not affected when electrolytic lesions were placed in the medial septum. Since the gene encoding amyloid precursor protein has been localized to mouse chromosome 16, the authors also examined the expression of this gene in the brains of mouse embryos with trisomy 16 and trisomy 19 at 15 days of gestation. RNA gel blot analysis and in situ hybridization showed a marked increase in amyloid precursor protein mRNA in the trisomy 16 mouse head and brain when compared with euploid littermates or with trisomy 19 mice.

  18. Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

    Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville

    2014-01-01

    Background The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. Objective To investigate the role of soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings. Methods The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results Lumbar CSF levels of sAPPα were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = −0.295, p = 0.003) and lumbar (r = −0.356, p = 0.01) samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure

  19. Maternal interaction style in affective disordered, physically ill, and normal women.

    PubMed

    Hamilton, E B; Jones, M; Hammen, C

    1993-09-01

    Affective style (AS) and communication deviance (CD) have been suggested as markers of dysfunctional family environments that may be associated with psychiatric illness. Studies have focused mainly on parental responses during family interactions when an offspring is the identified patient. The present study is unique in examining AS and CD in mothers with unipolar depression, bipolar disorder, or chronic physical illness, and in normal controls. The sample consisted of 64 mothers with children ages 8 to 16. Unipolar mothers were more likely to show negative AS than were any other maternal group. There were no group differences for CD. Chronic stress, few positive life events, and single parenting were associated with AS. CD was associated solely with lower socioeconomic status. Results suggest that dysfunctional interactions are determined not only by maternal psychopathology, but also by an array of contextual factors that are related to the quality of the family environment.

  20. Effect of 2% Chlorhexidine Digluconate on the Bond Strength to Normal versus Caries-Affected Dentin

    PubMed Central

    Komori, Paula C. P.; Pashley, David H.; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; de Goes, Mario Fernando; Wang, Linda; Carrilho, Marcela R.

    2013-01-01

    SUMMARY This study evaluated the effect of 2% chlorhexidine digluconate (CHX) used as a therapeutic primer on the long-term bond strengths of two etch-and-rinse adhesives to normal (ND) and caries-affected (CAD) dentin. Forty extracted human molars with coronal carious lesions, surrounded by normal dentin, were selected for this study. Flat surfaces of two types of dentin (i.e. ND and CAD) were prepared with a water-cooled high speed diamond disc, and then acid-etched, rinsed and air-dried. In control groups, dentin was re-hydrated with distilled water, blot-dried and bonded with a three-step (Scotchbond Multi-Purpose-MP) or a two-step (Single Bond 2-SB) etch-and-rinse adhesive. In experimental groups, dentin was re-hydrated with 2% CHX (60 s), blot-dried and bonded with the same adhesives. Resin composite build-ups were made. Specimens were prepared for microtensile bond testing in accordance with the non-trimming technique and then tested either immediately or after 6-month storage in artificial saliva. Data were analyzed by ANOVA/Bonferroni tests (α = 0.05). CHX did not affect the immediate bond strength to ND or CAD (p>0.05). CHX treatment significantly lowered the loss of bond strength after 6 months seen in control bonds for ND (p<0.05), but it did not alter the bond strength of CAD (p>0.05). Application of MP on CHX-treated ND or CAD produced bonds that did not change over 6 months of storage. PMID:19363971

  1. Brain aging in normal Egyptians: cognition, education, personality, genetic and immunological study.

    PubMed

    Elwan, Osamah; Madkour, Obsis; Elwan, Fadia; Mostafa, Mervat; Abbas Helmy, Azza; Abdel-Naseer, Maged; Abdel Shafy, Sanaa; El Faiuomy, Nervana

    2003-07-15

    Studying the cognitive and immunological changes that occur in old age as well as genetic function have been considered an important subject to differentiate between normal brain aging and early dementia especially Alzheimer's disease. The aim of this study is to stress on age-related neuropsychological and electrophysiological (P(300)) changes in normal Egyptian subjects, to throw light on the value of genetic (Apo-E(4) genotype) and immunological markers [interleukin-6 (IL-6) and intercellular adhesion molecules (ICAM-1) in the serum] as tools used in early detection of cognitive decline in cerebral aging. Ninety-four normal Egyptian subjects (below and above 60 years) were submitted to the following: (1) neuropsychological tests for testing memory, perception, psychomotor performance and attention, (2) Eysenck Personality Questionnaire (EPQ) for personality traits, (3) event-related potential study (P(300), latency and amplitude), (4) genetic test for detection of Apolipoprotein E genotype and (5) immunological studies including detection of the level of IL-6 and ICAM-1 in serum. There was a significant impairment of memory, psychomotor performance and perception in elderly subjects particularly males and subjects with low level of education. Regarding personality, significantly high scores were obtained in neuroticism scale of EPQ in elderly subjects. Apo-E(3)/E(3) was the most common genotype encountered in Egyptian subjects (49.1%). It was found that subjects with Apo-E(4) genotype did significantly worse in scores of intentional memory test (sensory memory) when compared with other genotypes. Statistically significant impairment in attention and sensory memory was found in subjects with high IL-6 level. This could not be detected in subjects with high ICAM-1 level. In conclusion, advancing age and lower levels of education are considered risk factors for cognitive decline in normal brain aging. Neuropsychological tests remain as the highly sensitive tools

  2. Acetylome regulation by sirtuins in the brain: from normal physiology to aging and pathology.

    PubMed

    Michan, Shaday

    2013-01-01

    Our understanding of the magnitude and physiological significance of proteome lysine acetylation remained incipient for five decades since it was first described. State-of-the-art methodologies, ranging from functional genomics to large-scale proteomics, have recently uncovered that this modification is more broadly represented in proteins than previously recognized, thus constituting the "acetylome." At present, it is estimated that acetylome covers only one tenth of the proteome, however, due its potential significance in physiology is capturing great attention. The first components of the cellular machinery, which finely orchestrate acetylome homeostasis, were identified by the end of last century. Since then, the majority of our growing knowledge concerning the physiological relevance of proteome reversible acetylation comes from the study of sirtuins, a unique type of lysine deacetylase that uses NAD(+). Sirtuins participate in a variety of cellular processes, ranging from transcription, DNA repair, energy balance, mitochondrial biogenesis and cell division, to apoptosis, autophagy and aging. Within the brain, besides their widespread epigenetic effects of dynamically modifying histones, sirtuins also target a variety of non-histone proteins either commonly deregulated in pathologies, or that participate in normal cerebral functions. For example, they modulate critical elements of the circadian rhythms, neurogenesis, synapses, cognition, serotonin synthesis, myelination, and proteins involved in neuropathology. Acetylome dynamics, and its regulation by sirtuins, may also help to better understand the molecular mechanisms underlying brain aging. This work reviews the pathways as orchestrated by the interplay between acetylome and sirtuins in the brain, from physiology involvement, to aging processes, and pathological settings.

  3. EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions

    PubMed Central

    Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

    2014-01-01

    For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

  4. Detecting Brain Growth Patterns in Normal Children using Tensor-Based Morphometry

    PubMed Central

    Hua, Xue; Leow, Alex D.; Levitt, Jennifer G.; Caplan, Rochelle; Thompson, Paul M.; Toga, Arthur W.

    2010-01-01

    Previous magnetic resonance imaging (MRI)-based volumetric studies have shown age-related increases in the volume of total white matter and decreases in the volume of total gray matter of normal children. Recent adaptations of image analysis strategies enable the detection of human brain growth with improved spatial resolution. In this article, we further explore the spatio-temporal complexity of adolescent brain maturation with tensor-based morphometry. By utilizing a novel non-linear elastic intensity-based registration algorithm on the serial structural MRI scans of 13 healthy children, individual Jacobian growth maps are generated and then registered to a common anatomical space. Statistical analyses reveal significant tissue growth in cerebral white matter, contrasted with gray matter loss in parietal, temporal, and occipital lobe. In addition, a linear regression with age and gender suggests a slowing down of the growth rate in regions with the greatest white matter growth. We demonstrate that a tensor-based Jacobian map is a sensitive and reliable method to detect regional tissue changes during development. PMID:18064588

  5. PMCA activity and membrane tubulin affect deformability of erythrocytes from normal and hypertensive human subjects.

    PubMed

    Monesterolo, Noelia E; Nigra, Ayelen D; Campetelli, Alexis N; Santander, Verónica S; Rivelli, Juan F; Arce, Carlos A; Casale, Cesar H

    2015-11-01

    Our previous studies demonstrated formation of a complex between acetylated tubulin and brain plasma membrane Ca(2+)-ATPase (PMCA), and the effect of the lipid environment on structure of this complex and on PMCA activity. Deformability of erythrocytes from hypertensive human subjects was reduced by an increase in membrane tubulin content. In the present study, we examined the regulation of PMCA activity by tubulin in normotensive and hypertensive erythrocytes, and the effect of exogenously added diacylglycerol (DAG) and phosphatidic acid (PA) on erythrocyte deformability. Some of the key findings were that: (i) PMCA was associated with tubulin in normotensive and hypertensive erythrocytes, (ii) PMCA enzyme activity was directly correlated with erythrocyte deformability, and (iii) when tubulin was present in the erythrocyte membrane, treatment with DAG or PA led to increased deformability and associated PMCA activity. Taken together, our findings indicate that PMCA activity is involved in deformability of both normotensive and hypertensive erythrocytes. This rheological property of erythrocytes is affected by acetylated tubulin and its lipid environment because both regulate PMCA activity.

  6. Impact of Millimeter-Level Margins on Peripheral Normal Brain Sparing for Gamma Knife Radiosurgery

    SciTech Connect

    Ma, Lijun; Sahgal, Arjun; Larson, David A.; Pinnaduwage, Dilini; Fogh, Shannon; Barani, Igor; Nakamura, Jean; McDermott, Michael; Sneed, Penny

    2014-05-01

    Purpose: To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. Methods and Materials: A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Results: Confirmatory correlation between the nominal target radius (ie, R{sub T}) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/R{sub T}, where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R{sup 2} >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/R{sub T} values for the target. Conclusions: Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets.

  7. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

    PubMed

    Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

    2007-12-11

    Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

  8. Trajectories of cortical thickness maturation in normal brain development – The importance of quality control procedures

    PubMed Central

    Ducharme, Simon; Albaugh, Matthew D.; Nguyen, Tuong-Vi; Hudziak, James J.; Mateos-Pérez, J. M.; Labbe, Aurelie; Evans, Alan C.; Karama, Sherif

    2015-01-01

    Several reports have described cortical thickness (CTh) developmental trajectories, with conflicting results. Some studies have reported inverted-U shape curves with peaks of CTh in late childhood to adolescence, while others suggested predominant monotonic decline after age 6. In this study, we reviewed CTh developmental trajectories in the NIH MRI Study of Normal Brain Development, and in a second step evaluated the impact of post-processing quality control (QC) procedures on identified trajectories. The quality-controlled sample included 384 individual subjects with repeated scanning (1–3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models. The majority of brain regions showed linear monotonic decline of CTh. There were few areas of cubic trajectories, mostly in bilateral temporo-parietal areas and the right prefrontal cortex, in which CTh peaks were at, or prior to, age 8. When controlling for total brain volume, CTh trajectories were even more uniformly linear. The only sex difference was faster thinning of occipital areas in boys compared to girls. The best-fit model for whole brain mean thickness was a monotonic decline of 0.027 mm per year. QC procedures had a significant impact on identified trajectories, with a clear shift toward more complex trajectories when including all scans without QC (n=954). Trajectories were almost exclusively linear when using only scans that passed the most stringent QC (n=598). The impact of QC probably relates to decreasing the inclusion of scans with CTh underestimation secondary to movement artifacts, which are more common in younger subjects. In summary, our results suggest that CTh follows a simple linear decline in most cortical areas by age 5, and all areas by age 8. This study further supports the crucial importance of implementing post-processing QC in CTh studies of development, aging

  9. Trajectories of cortical thickness maturation in normal brain development--The importance of quality control procedures.

    PubMed

    Ducharme, Simon; Albaugh, Matthew D; Nguyen, Tuong-Vi; Hudziak, James J; Mateos-Pérez, J M; Labbe, Aurelie; Evans, Alan C; Karama, Sherif

    2016-01-15

    Several reports have described cortical thickness (CTh) developmental trajectories, with conflicting results. Some studies have reported inverted-U shape curves with peaks of CTh in late childhood to adolescence, while others suggested predominant monotonic decline after age 6. In this study, we reviewed CTh developmental trajectories in the NIH MRI Study of Normal Brain Development, and in a second step, evaluated the impact of post-processing quality control (QC) procedures on identified trajectories. The quality-controlled sample included 384 individual subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models. The majority of brain regions showed linear monotonic decline of CTh. There were few areas of cubic trajectories, mostly in bilateral temporo-parietal areas and the right prefrontal cortex, in which CTh peaks were at, or prior to, age 8. When controlling for total brain volume, CTh trajectories were even more uniformly linear. The only sex difference was faster thinning of occipital areas in boys compared to girls. The best-fit model for whole brain mean thickness was a monotonic decline of 0.027mm per year. QC procedures had a significant impact on identified trajectories, with a clear shift toward more complex trajectories (i.e., quadratic or cubic) when including all scans without QC (n=954). Trajectories were almost exclusively linear when using only scans that passed the most stringent QC (n=598). The impact of QC probably relates to decreasing the inclusion of scans with CTh underestimation secondary to movement artifacts, which are more common in younger subjects. In summary, our results suggest that CTh follows a simple linear decline in most cortical areas by age 5, and all areas by age 8. This study further supports the crucial importance of implementing post-processing QC in CTh studies

  10. Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

    PubMed Central

    Cooper, Arthur J. L.; Jeitner, Thomas M.

    2016-01-01

    Glutamate is present in the brain at an average concentration—typically 10–12 mM—far in excess of those of other amino acids. In glutamate-containing vesicles in the brain, the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter, the concentration of this amino acid in the cerebral extracellular fluid must be kept low—typically µM. The remarkable gradient of glutamate in the different cerebral compartments: vesicles > cytosol/mitochondria > extracellular fluid attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate catabolism and synthesis in well-defined cellular and subcellular compartments in the brain. A major route for glutamate and ammonia removal is via the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter γ-aminobutyrate (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine amide, the direction of the glutamate dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia, there is a large increase in cerebral glutamine content, but only small changes in the levels of glutamate and α-ketoglutarate. Thus, the channeling of glutamate toward glutamine during hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5-carbon units is accomplished in part by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate

  11. Accumulation of intraneuronal amyloid-β is common in normal brain.

    PubMed

    Blair, Jeffrey A; Siedlak, Sandra L; Wolfram, Julie A; Nunomura, Akihiko; Castellani, Rudy J; Ferreira, Sergio T; Klein, William L; Wang, Yang; Casadesus, Gemma; Smith, Mark A; Perry, George; Zhu, Xiongwei; Lee, Hyoung-gon

    2014-05-01

    Intraneuronal amyloid-β (iAβ) accumulation has been demonstrated in Alzheimer disease (AD). Although extracellular amyloid plaques composed primarily of aggregated amyloid-β are one of the main pathological features of AD, functional characterization of iAβ is still lacking. In this study, we identified the normal distribution of iAβ through an analysis of hippocampal sections from a series of over 90 subjects with diverse antemortem clinical findings. In addition to AD cases, iAβ in pyramidal neurons was readily and reproducibly demonstrated in the majority of control cases. Similar findings for controls were made across all ages, spanning from infants to the elderly. There was no correlation of iAβ between gender, postmortem interval, or age. While the possible pathophysiological significance of iAβ accumulation in AD remains to be elucidated, careful examination of iAβ found in the normal brain may be informative for determining the biological role of iAβ and how this function changes during disease. Current findings support a physiological role for iAβ in neuronal function over the entire lifespan.

  12. mTOR signaling and its roles in normal and abnormal brain development.

    PubMed

    Takei, Nobuyuki; Nawa, Hiroyuki

    2014-01-01

    Target of rapamycin (TOR) was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mammalian TOR (mTOR). mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid) synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

  13. Neonatal hypothyroidism affects the adenine nucleotides metabolism in astrocyte cultures from rat brain.

    PubMed

    Braganhol, Elizandra; Bruno, Alessandra Nejar; Bavaresco, Luci; Barreto-Chaves, Maria Luiza M; Sarkis, João José Freitas; Battastini, Ana Maria Oliveira

    2006-04-01

    Neonatal hypothyroidism is associated with multiple and severe brain alterations. We recently demonstrated a significant increase in hydrolysis of AMP to adenosine in brain of hypothyroid rats at different ages. However, the origin of this effect was unclear. Considering the effects of adenine nucleotides to brain functions and the harmful effects of neonatal hypothyroidism to normal development of the central nervous system, in this study we investigated the metabolism of adenine nucleotides in hippocampal, cortical and cerebellar astrocyte cultures from rats submitted to neonatal hypothyroidism. ATP and AMP hydrolysis were enhanced by 52 and 210%, respectively, in cerebellar astrocytes from hypothyroid rats. In hippocampus of hypothyroid rats, the 47% increase in AMP hydrolysis was significantly reverted when the astrocytes were treated with T3. Therefore, the imbalance in the ATP and adenosine levels in astrocytes, during brain development, may contribute to some of the effects described in neonatal hypothyroidism.

  14. Variations of brain activities of acupuncture to TE5 of left hand in normal subjects.

    PubMed

    Hsu, Sheng-Feng; Chen, Chien-Yue; Ke, Ming-Da; Huang, Chien-Hsun; Sun, Yuan-Ting; Lin, Jaung-Geng

    2011-01-01

    This paper presents the evident effects of acupoint stimulation, using EEG (electroencephalogram) measurements. With acupuncture stimulation and the EEG measurement on the same meridian, EEG is able to accurately detect the effects of acupunctural point stimulation on brain waves. In this study, 24 subjects without heart or neural diseases were randomly separated into two groups of 12, named test and control groups. Similar procedures are performed; the subjects lay on a bed with eyes closed for ten minutes as the baseline. The test group received acupuncture at their Waiguan points (TE5) on their left hands for 20 minutes, while the control group did not. EEGs are recorded during pre-acupuncture, acupuncture stimulation and post-acupuncture stimulation periods. The EEG electrodes are at the T3, T4, O1 and O2 locations. Continuous wavelet transformation analysis is adopted; therefore, EEGs are divided into the following bands: δ (0.5-4HZ), θ (4-8HZ), α (8-13HZ) and β (13-30HZ). During acupuncture stimulation, the θ energy is increased and had statistical differences at all electrode points, T3, T4, O1 and O2. Upon removing the needle, the energy at the T3 and T4 points slowly declined and revealed obvious statistical differences. During acupuncture, only α energy has been noted to have statistical difference and it was increased at the T3 point. However, the energy was decreased and had no statistical difference after five minutes. Acupuncture is proven to be able to affect brain waves, as the stimulation might have changed the tissues between the cranium and scalp; therefore, the brain waves are detected more easily.

  15. PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments affecting ketosis.

    PubMed

    Bentourkia, M'hamed; Tremblay, Sébastien; Pifferi, Fabien; Rousseau, Jacques; Lecomte, Roger; Cunnane, Stephen

    2009-04-01

    Normally, the brain's fuel is glucose, but during fasting it increasingly relies on ketones (beta-hydroxybutyrate, acetoacetate, and acetone) produced in liver mitochondria from fatty acid beta-oxidation. Although moderately raised blood ketones produced on a very high fat ketogenic diet have important clinical effects on the brain, including reducing seizures, ketone metabolism by the brain is still poorly understood. The aim of the present work was to assess brain uptake of carbon-11-labeled acetoacetate (11C-acetoacetate) by positron emission tomography (PET) imaging in the intact, living rat. To vary plasma ketones, we used three dietary conditions: high carbohydrate control diet (low plasma ketones), fat-rich ketogenic diet (raised plasma ketones), and 48-h fasting (raised plasma ketones). 11C-acetoacetate metabolism was measured in the brain, heart, and tissue in the mouth area. Using 11C-acetoacetate and small animal PET imaging, we have noninvasively quantified an approximately seven- to eightfold enhanced brain uptake of ketones on a ketogenic diet or during fasting. This opens up an opportunity to study brain ketone metabolism in humans.

  16. Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample.

    PubMed

    Chaves, M L; Ilha, D; Maia, A L; Motta, E; Lehmen, R; Oliveira, L M

    1999-09-01

    The main objective of the present study was to evaluate the diagnostic value (clinical application) of brain measures and cognitive function. Alzheimer and multi-infarct patients (N = 30) and normal subjects over the age of 50 (N = 40) were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.

  17. Rapid and Quantitative Assay of Amyloid-Seeding Activity in Human Brains Affected with Prion Diseases

    PubMed Central

    Takatsuki, Hanae; Satoh, Katsuya; Sano, Kazunori; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Ishibashi, Daisuke; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Atarashi, Ryuichiro; Nishida, Noriyuki

    2015-01-01

    The infectious agents of the transmissible spongiform encephalopathies are composed of amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts of PrPSc seeds in tissues/body fluids of patients or animals. Using this in vitro PrP-amyloid amplification assay, we quantitated the seeding activity of affected human brains. End-point assay using serially diluted brain homogenates of sporadic Creutzfeldt–Jakob disease patients demonstrated that 50% seeding dose (SD50) is reached approximately 1010/g brain (values varies 108.79–10.63/g). A genetic case (GSS-P102L) yielded a similar level of seeding activity in an autopsy brain sample. The range of PrPSc concentrations in the samples, determined by dot-blot assay, was 0.6–5.4 μg/g brain; therefore, we estimated that 1 SD50 unit was equivalent to 0.06–0.27 fg of PrPSc. The SD50 values of the affected brains dropped more than three orders of magnitude after autoclaving at 121°C. This new method for quantitation of human prion activity provides a new way to reduce the risk of iatrogenic prion transmission. PMID:26070208

  18. Dynamic changes in brain activations and functional connectivity during affectively different tactile stimuli.

    PubMed

    Hua, Qing-Ping; Zeng, Xiang-Zhu; Liu, Jian-Yu; Wang, Jin-Yan; Guo, Jian-You; Luo, Fei

    2008-01-01

    In the present study, we compared brain activations produced by pleasant, neutral and unpleasant touch, to the anterior lateral surface of lower leg of human subjects. It was found that several brain regions, including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), as well as contralateral middle and posterior insula cortex were commonly activated under the three touch conditions. In addition, pleasant and unpleasant touch conditions shared a few brain regions including the contralateral posterior parietal cortex (PPC) and bilateral premotor cortex (PMC). Unpleasant touch specifically activated a set of pain-related brain regions such as contralateral supplementary motor area (SMA) and dorsal parts of bilateral anterior cingulated cortex, etc. Brain regions specifically activated by pleasant touch comprised bilateral lateral orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), intraparietal cortex and left dorsal lateral prefrontal cortex (DLPFC). Using a novel functional connectivity model based on graph theory, we showed that a series of brain regions related to affectively different touch had significant functional connectivity during the resting state. Furthermore, it was found that such a network can be modulated between affectively different touch conditions.

  19. Alcohol-induced brain growth restrictions (microencephaly) were not affected by concurrent exposure to cocaine during the brain growth spurt.

    PubMed

    Chen, W J; Andersen, K H; West, J R

    1994-09-01

    The prevalence of concomitant use of alcohol and cocaine among drug abusers has raised concern about the possible increased risk of fetal damage. The aim of this study was to assess the interactive effects of alcohol and cocaine on lethality, somatic growth, and brain growth using an animal model system. Sprague-Dawley rat pups were used as subjects. They were randomly assigned to 1 of the 9 artificially reared groups which varied with respect to the combination treatments of cocaine (0, 40, or 60 mg/kg) and alcohol (0, 3.3, or 4.5 g/kg). All artificially reared pups were given daily cocaine and alcohol treatments during a major part of the brain growth spurt period (postnatal days 4-9). An additional group of suckled control animals raised by their natural dams was included to control for artificial rearing. The results are summarized as follows: 1) Drug-induced lethality was higher in cocaine-treated groups when compared with non-cocaine-treated groups, and the concurrent administration of high doses of alcohol and cocaine significantly increased the mortality rate. 2) Somatic growth, in terms of body weight, was not affected by alcohol, cocaine, or the combination of both drugs using the artificial rearing technique. 3) Alcohol exposure during this brain growth spurt period significantly reduced whole brain weight, as well as forebrain, cerebellum, and brain stem weights. 4) In contrast to alcohol, cocaine failed to exert a detrimental effect on brain weight measures during this early postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. White matter hyperintensities and normal-appearing white matter integrity in the aging brain.

    PubMed

    Maniega, Susana Muñoz; Valdés Hernández, Maria C; Clayden, Jonathan D; Royle, Natalie A; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S; Gow, Alan J; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2015-02-01

    White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe.

  1. Affection of Fundamental Brain Activity By Using Sounds For Patients With Prosodic Disorders: A Pilot Study

    NASA Astrophysics Data System (ADS)

    Imai, Emiko; Katagiri, Yoshitada; Seki, Keiko; Kawamata, Toshio

    2011-06-01

    We present a neural model of the production of modulated speech streams in the brain, referred to as prosody, which indicates the limbic structure essential for producing prosody both linguistically and emotionally. This model suggests that activating the fundamental brain including monoamine neurons at the basal ganglia will potentially contribute to helping patients with prosodic disorders coming from functional defects of the fundamental brain to overcome their speech problem. To establish effective clinical treatment for such prosodic disorders, we examine how sounds affect the fundamental activity by using electroencephalographic measurements. Throughout examinations with various melodious sounds, we found that some melodies with lilting rhythms successfully give rise to the fast alpha rhythms at the electroencephalogram which reflect the fundamental brain activity without any negative feelings.

  2. Affective neuroscience of the emotional BrainMind: evolutionary perspectives and implications for understanding depression

    PubMed Central

    Panksepp, Jaak

    2010-01-01

    Cross-species affective neuroscience studies confirm that primary-process emotional feelings are organized within primitive subcortical regions of the brain that are anatomically, neurochemically, and functionally homologous in all mammals that have been studied. Emotional feelings (affects) are intrinsic values that inform animals how they are faring in the quest to survive. The various positive affects indicate that animals are returning to “comfort zones” that support survival, and negative affects reflect “discomfort zones” that indicate that animals are in situations that may impair survival. They are ancestral tools for living - evolutionary memories of such importance that they were coded into the genome in rough form (as primary brain processes), which are refined by basic learning mechanisms (secondary processes) as well as by higher-order cognitions/thoughts (tertiary processes). To understand why depression feels horrible, we must fathom the affective infrastructure of the mammalian brain. Advances in our understanding of the nature of primary-process emotional affects can promote the development of better preclinical models of psychiatric disorders and thereby also allow clinicians new and useful ways to understand the foundational aspects of their clients' problems. These networks are of clear importance for understanding psychiatric disorders and advancing psychiatric practice. PMID:21319497

  3. Developing Connections for Affective Regulation: Age-Related Changes in Emotional Brain Connectivity

    ERIC Educational Resources Information Center

    Perlman, Susan B.; Pelphrey, Kevin A.

    2011-01-01

    The regulation of affective arousal is a critical aspect of children's social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of "hot" executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional…

  4. Foods and food constituents that affect the brain and human behavior

    NASA Technical Reports Server (NTRS)

    Lieberman, Harris R.; Wurtman, Richard J.

    1986-01-01

    Until recently, it was generally believed that brain function was usually independent of day-to-day metabolic changes associated with consumption of food. Although it was acknowledged that peripheral metabolic changes associated with hunger or satiety might affect brain function, other effects of foods on the brain were considered unlikely. However, in 1971, Fernstrom and Wurtman discovered that under certain conditions, the protein-to-carbohydrate ratio of a meal could affect the concentration of a particular brain neurotransmitter. That neurotransmitter, serotonin, participates in the regulation of a variety of central nervous system (CNS) functions including sleep, pain sensitivity, aggression, and patterns of nutrient selection. The activity of other neurotransmitter systems has also been shown to be, under certain conditions, affected by dietary constituents which are given either as ordinary foods or in purified form. For example, the CNS turnover of two catecholamine neurotransmitters, dopamine and norepinephrine, can be altered by ingestion of their amino acid precursor, tyrosine, when neurons that release these monoamines are firing frequently. Similarly, lecithin, a dietary source of choline, and choline itself have been shown to increase the synthesis of acetylcholine when cholinergic neurons are very active. It is possible that other neurotransmitters could also be affected by precursor availability or other, as yet undiscovered peripheral factors governed by food consumption. The effects of food on neurotransmitters and behavior are discussed.

  5. Affective-Motivational Brain Responses to Direct Gaze in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Kylliainen, Anneli; Wallace, Simon; Coutanche, Marc N.; Leppanen, Jukka M.; Cusack, James; Bailey, Anthony J.; Hietanen, Jari K.

    2012-01-01

    Background: It is unclear why children with autism spectrum disorders (ASD) tend to be inattentive to, or even avoid eye contact. The goal of this study was to investigate affective-motivational brain responses to direct gaze in children with ASD. To this end, we combined two measurements: skin conductance responses (SCR), a robust arousal…

  6. The Sad, the Angry, and the Asymmetrical Brain: Dichotic Listening Studies of Negative Affect and Depression

    ERIC Educational Resources Information Center

    Gadea, Marien; Espert, Raul; Salvador, Alicia; Marti-Bonmati, Luis

    2011-01-01

    Dichotic Listening (DL) is a valuable tool to study emotional brain lateralization. Regarding the perception of sadness and anger through affective prosody, the main finding has been a left ear advantage (LEA) for the sad but contradictory data for the anger prosody. Regarding an induced mood in the laboratory, its consequences upon DL were a…

  7. MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

    SciTech Connect

    Wu, Q; Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N

    2015-06-15

    Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.

  8. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  9. Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2016-10-01

    Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

  10. Segmentation and classification of normal-appearing brain: how much is enough?

    NASA Astrophysics Data System (ADS)

    Glass, John O.; Reddick, Wilburn E.; Ji, Qing; Glas, Lauren S.

    2002-05-01

    In this study, subsets of MR slices were examined to assess their ability to optimally predict the total cerebral volume of gray matter, white matter and CSF. Patients underwent a clinical imaging protocol consisting of T1-, T2-, PD-, and FLAIR-weighted images after obtaining informed consent. MR imaging sets were registered, RF-corrected, and then analyzed with a hybrid neural network segmentation and classification algorithm to identify normal brain parenchyma. After processing the data, the correlation between the image subsets and the total cerebral volumes of gray matter, white matter and CSF were examined. The 29 subjects (18F, 11M) assessed in this study were 1.7 ? 18.7 (median = 5.2) years of age. The five subsets accounted for 5%, 15%, 24%, 56%, and 79% of the total cerebral volume. The predictive correlation for gray matter, white matter, and CSF in each of these subsets were: 5% (R= 0.94, 0.92, 0.91), 15% (R= 0.93, 0.95, 0.94), 24% (R= 0.92, 0.95, 0.94), 56% (R= 0.75, 0.95, 0.89), and 79% (R= 0.89, 0.98, 0.99) respectively. All subsets of slices examined were significantly correlated (p<0.001) with the total cerebral volume of gray matter, white matter, and CSF.

  11. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

    PubMed

    Aug, Argo; Altraja, Siiri; Kilk, Kalle; Porosk, Rando; Soomets, Ursel; Altraja, Alan

    2015-01-01

    E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

  12. Crosstalk between normal and tumoral brain cells. Effect on sex steroid metabolism.

    PubMed

    Melcangi, R C; Cavarretta, I; Magnaghi, V; Ballabio, M; Martini, L; Motta, M

    1998-02-01

    The present article shows for the first time that two cell lines derived respectively from a rat glioma (C6 cell line) and from a human astrocytoma (1321N1 cell line) are able to convert testosterone and progesterone into their corresponding 5 alpha-reduced metabolites dihydrotestosterone and dihydroprogesterone. Moreover, both cell lines are also able to convert these metabolites further into their corresponding 3 alpha-OH derivatives, 5 alpha-androstan-3 alpha, 7 beta-diol (3 alpha-diol) and tetrahydroprogesterone. On the basis of these observations, the possibility that secretory products of normal and tumoral brain cells might be able to influence steroid metabolism occurring in the two glial cell lines previously mentioned as well as in fetal rat neurons and in neonatal rat type 1 astrocytes has been considered. To this purpose, cultures of the different cellular types have been exposed to the conditioned medium in which the other cells were grown. The results obtained indicate that: 1. Neurons are able to stimulate, in a statistically significant fashion, the formation of dihydrotestosterone (DHT), 3 alpha-diol, and tetrahydraprogesterone (THP) in C6 cells. 2. Type 1 astrocytes, on the contrary, are unable to modify steroid metabolism in C6 cells. 3. C6 cell product(s) decrease(s) the formation of DHP in type 1 astrocytes, without modifying that of DHT. 4. C6 cells do not influence the metabolism of testosterone (T) and progesterone (P) in neurons. In conclusion, the present observations show that the conditioned medium of normal neurons is able to increase the metabolism of testosterone and progesterone occurring in a tumoral glial cell line, and that the conditioned media of the two tumoral cell lines analyzed are able to decrease the conversion of P into DHP occurring in normal type 1 astrocytes. The surprising result that these conditioned media do not alter the formation of DHT is discussed. Work is presently in progress to identify the principle

  13. FMRI Brain Activation in a Finnish Family with Specific Language Impairment Compared with a Normal Control Group

    ERIC Educational Resources Information Center

    Hugdahl, Kenneth; Gundersen, Hilde; Brekke, Cecilie; Thomsen, Tormod; Rimol, Lars Morten; Ersland, Lars; Niemi, Jussi

    2004-01-01

    The aim of the present study was to investigate differences in brain activation in a family with SLI as compared to intact individuals with normally developed language during processing of language stimuli. Functional magnetic resonance imaging (fMRI) was used to monitor changes in neuronal activation in temporal and frontal lobe areas in 5…

  14. NUTRIENT PATTERNS AND BRAIN BIOMARKERS OF ALZHEIMER’S DISEASE IN COGNITIVELY NORMAL INDIVIDUALS

    PubMed Central

    BERTI, V.; MURRAY, J.; DAVIES, M.; SPECTOR, N.; TSUI, W.H.; LI, Y.; WILLIAMS, S.; PIRRAGLIA, E.; VALLABHAJOSULA, S.; MCHUGH, P.; PUPI, A.; DE LEON, M.J.; MOSCONI, L.

    2015-01-01

    Objectives Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer’s disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. Design Cross-sectional study. Setting Manhattan (broader area). Participants Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. Measurements Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. Results None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB&Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE&PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants&Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12&D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12&D

  15. Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features

    PubMed Central

    Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

    2016-01-01

    The ‘neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe−/− × Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n ≥5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe−/− × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe−/− × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe−/− × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments. PMID:26728570

  16. Waterborne lead affects circadian variations of brain neurotransmitters in fathead minnows

    SciTech Connect

    Spieler, R.E.; Russo, A.C.; Weber, D.N.

    1995-09-01

    Lead is a potent neurotoxin affecting brain levels of a number of vertebrate neurotransmitters. Reports on these effects are, however, not consistent either among or within species. For example, with lead-intoxicated rats there are reports of decreased acetylcholine (ACh) release and decreased ACh brain levels as well as reports of increased levels or no change in levels. Also, with rats there are reports of increased levels, decreased levels, or no change in brain catecholamines, with lead producing similar changes in both norephinephrine (NE) and dopamine (DA) in some cases and differences in response between the two in others. Although most early reports dealt with whole brain levels, reports on neurotransmitter levels in specific brain regions can be equally conflicting. Similar sorts of discrepancies exist among studies with fishes. Much of the variation among studies on lead effects on neurotransmitters is, no doubt, due to differences among the studies in variables such as: species, age, dosage and duration, route of administration. However, lead can apparently affect circadian locomotor rhythms of both rats and fishes. Therefore, another possible cause for the variation among studies is that there is an interaction among dosage, sampling time and endogenous rhythms. A lead-produced phase shift or disruption in endogenous neurotransmitter rhythms could in turn elicit a host of varying results and interpretations depending on the circadian time of sampling. We elected to examine this possibility in the fathead minnow, Pimephales promelas, a freshwater species widely used for toxicity studies. 15 refs., 3 figs.

  17. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

    PubMed

    Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohan Mohapatra, Tribhuvan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Kumar Rai, Sunil; Monti, Maria; Harlalka, Gaurav V; Simpson, Michael A; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A; Chioza, Barry A; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G; Pucci, Piero; Houlden, Henry; Lupski, James R; Crosby, Andrew H; Baple, Emma L

    2017-02-28

    PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.

  18. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment

    PubMed Central

    Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohan Mohapatra, Tribhuvan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E.; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Kumar Rai, Sunil; Monti, Maria; Harlalka, Gaurav V.; Simpson, Michael A.; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A.; Chioza, Barry A.; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G.; Pucci, Piero; Houlden, Henry; Lupski, James R.; Crosby, Andrew H.

    2017-01-01

    Abstract PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation. PMID:28334956

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

    PubMed Central

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

    2017-01-01

    Mate choice decisions are central in sexual selection theory aimed to understand how sexual traits evolve and their role in evolutionary diversification. We test the hypothesis that brain size and cognitive ability are important for accurate assessment of partner quality and that variation in brain size and cognitive ability underlies variation in mate choice. We compared sexual preference in guppy female lines selected for divergence in relative brain size, which we have previously shown to have substantial differences in cognitive ability. In a dichotomous choice test, large-brained and wild-type females showed strong preference for males with color traits that predict attractiveness in this species. In contrast, small-brained females showed no preference for males with these traits. In-depth analysis of optomotor response to color cues and gene expression of key opsins in the eye revealed that the observed differences were not due to differences in visual perception of color, indicating that differences in the ability to process indicators of attractiveness are responsible. We thus provide the first experimental support that individual variation in brain size affects mate choice decisions and conclude that differences in cognitive ability may be an important underlying mechanism behind variation in female mate choice. PMID:28345039

  20. Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single–Isocenter Volumetric Modulated Arc Therapy

    PubMed Central

    Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J.; Wen, Ning

    2016-01-01

    Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly. PMID:27688047

  1. Associations between early adrenarche, affective brain function and mental health in children.

    PubMed

    Whittle, Sarah; Simmons, Julian G; Byrne, Michelle L; Strikwerda-Brown, Cherie; Kerestes, Rebecca; Seal, Marc L; Olsson, Craig A; Dudgeon, Paul; Mundy, Lisa K; Patton, George C; Allen, Nicholas B

    2015-09-01

    Early timing of adrenarche, associated with relatively high levels of Dehydroepiandrosterone (DHEA) in children, has been associated with mental health and behavioral problems. However, little is known about effects of adreneracheal timing on brain function. The aim of this study was to investigate the effects of early adrenarche (defined by high DHEA levels independent of age) on affective brain function and symptoms of psychopathology in late childhood (N = 83, 43 females, M age 9.53 years, s.d. 0.34 years). Results showed that higher DHEA levels were associated with decreased affect-related brain activity (i) in the mid-cingulate cortex in the whole sample, and (ii) in a number of cortical and subcortical regions in female but not male children. Higher DHEA levels were also associated with increased externalizing symptoms in females, an association that was partly mediated by posterior insula activation to happy facial expressions. These results suggest that timing of adrenarche is an important moderator of affect-related brain function, and that this may be one mechanism linking early adrenarche to psychopathology.

  2. Associations between early adrenarche, affective brain function and mental health in children

    PubMed Central

    Whittle, Sarah; Simmons, Julian G.; Byrne, Michelle L.; Strikwerda-Brown, Cherie; Kerestes, Rebecca; Seal, Marc L.; Olsson, Craig A.; Dudgeon, Paul; Mundy, Lisa K.; Patton, George C.

    2015-01-01

    Early timing of adrenarche, associated with relatively high levels of Dehydroepiandrosterone (DHEA) in children, has been associated with mental health and behavioral problems. However, little is known about effects of adreneracheal timing on brain function. The aim of this study was to investigate the effects of early adrenarche (defined by high DHEA levels independent of age) on affective brain function and symptoms of psychopathology in late childhood (N = 83, 43 females, M age 9.53 years, s.d. 0.34 years). Results showed that higher DHEA levels were associated with decreased affect-related brain activity (i) in the mid-cingulate cortex in the whole sample, and (ii) in a number of cortical and subcortical regions in female but not male children. Higher DHEA levels were also associated with increased externalizing symptoms in females, an association that was partly mediated by posterior insula activation to happy facial expressions. These results suggest that timing of adrenarche is an important moderator of affect-related brain function, and that this may be one mechanism linking early adrenarche to psychopathology. PMID:25678548

  3. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-11-26

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur.

  4. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

    PubMed Central

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. DOI: http://dx.doi.org/10.7554/eLife.11290.001 PMID:26609811

  5. Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness.

    PubMed

    Petruzzello, S J; Hall, E E; Ekkekakis, P

    2001-01-01

    Previous research has shown that regional brain activation, assessed via frontal electroencephalographic (EEG) asymmetry, predicts affective responsivity to aerobic exercise. To replicate and extend this work, in the present study we examined whether resting brain activation was associated with affective responses to an acute bout of aerobic exercise and the extent to which aerobic fitness mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n = 45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre- and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted positive affect (as measured by the energetic arousal subscale of the Activation Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG asymmetry predicted affect only in the high-fit group, suggesting the effect might be mediated by some factor related to fitness. It was also shown that subjects with relatively greater left frontal activation had significantly more energy (i.e., activated pleasant affect) following exercise than subjects with relatively greater right frontal activation. In conclusion, aerobic fitness influenced the relationship between resting frontal asymmetry and exercise-related affective responsivity.

  6. Child temperament, parent affect, and feeding in normal and overweight preschool children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite overwhelming evidence showing that parent emotional affect impacts parenting directives and child outcomes, little research has focused on the influence of parent affect on feeding as a mechanism in shaping children's eating patterns. Utilizing an instrument characterizing parent strategies ...

  7. Presenting Thin Media Models Affects Women's Choice of Diet or Normal Snacks

    ERIC Educational Resources Information Center

    Krahe, Barbara; Krause, Christina

    2010-01-01

    Our study explored the influence of thin- versus normal-size media models and of self-reported restrained eating behavior on women's observed snacking behavior. Fifty female undergraduates saw a set of advertisements for beauty products showing either thin or computer-altered normal-size female models, allegedly as part of a study on effective…

  8. Cerebral endothelial expression of Robo1 affects brain infiltration of polymorphonuclear neutrophils during mouse stroke recovery.

    PubMed

    Gangaraju, Sandhya; Sultan, Khadeejah; Whitehead, Shawn N; Nilchi, Ladan; Slinn, Jacqueline; Li, Xuesheng; Hou, Sheng T

    2013-06-01

    Increased brain infiltration of polymorphonuclear neutrophils (PMNs) occurs early after stroke and is important in eliciting brain inflammatory response during stroke recovery. In order to understand the molecular mechanism of PMN entry, we investigated the expression and requirement for Slit1, a chemorepulsive guidance cue, and its cognate receptor, Robo1, in a long-term recovery mouse model of cerebral ischemia. The expression levels of Robo1 were significantly decreased bilaterally at 24h following reperfusion. Robo1 expression levels remained suppressed in the ipsilateral cortex until 28d post MCAO-reperfusion, while the levels of Robo1 in the contralateral cortex recovered to the level of sham-operated mouse by 7d reperfusion. Circulating PMNs express high levels of Slit1, but not Robo1. Influx of PMNs into the ischemic core area occurred early (24h) after cerebral ischemia, when endothelial Robo1 expression was significantly reduced in the ischemic brain, indicating that Robo1 may form a repulsive barrier to PMN entry into the brain parenchyma. Indeed, blocking Slit1 on PMNs in a transwell migration assay in combination with an antibody blocking of Robo1 on human umbilical vein endothelial cells (HUVEC) significantly increased PMN transmigration during oxygen glucose deprivation, an in vitro model of ischemia. Collectively, in the normal brain, the presence of Slit1 on PMNs, and Robo1 on cerebral endothelial cells, generated a repulsive force to prevent the infiltration of PMNs into the brain. During stroke recovery, a transient reduction in Robo1 expression on the cerebral endothelial cells allowed the uncontrolled infiltration of Slit1-expressing PMNs into the brain causing inflammatory reactions.

  9. Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach

    PubMed Central

    Roldan-Valadez, Ernesto; Rios, Camilo; Cortez-Conradis, David; Favila, Rafael; Moreno-Jimenez, Sergio

    2014-01-01

    Background Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Methods Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. Results The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks’ λ = 0.324, χ2 (3) = 38.907, p < .001. The overall predictive accuracy was 92.7%. Conclusions We present a phase II study introducing a novel global approach using DTI-derived biomarkers of brain impairment. The final predictive model selected only three metrics: axial diffusivity, spherical tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases. PMID:24991202

  10. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

    PubMed Central

    Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  11. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity.

    PubMed

    Schmidt, André; Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  12. In vivo brain glucose measurements: differential normal pulse voltammetry with enzyme-modified carbon fiber microelectrodes.

    PubMed

    Netchiporouk, L I; Shram, N F; Jaffrezic-Renault, N; Martelet, C; Cespuglio, R

    1996-12-15

    The enzyme glucose oxidase was immobilized on the surface of carbon fiber microelectrodes (CFMEs) either by cross-linking in glutaraldehyde vapor or by enzyme entrapment in electropolymerized films of m-phenylenediamine or resorcinol. The cross-linked enzymatic layer was, in the given conditions, covered with an additional membrane of Nafion or cellulose acetate. The prepared glucose sensors were tested using differential normal pulse voltammetry (DNPV, in which the scan comprises successive double pulses ("prepulse and pulse"), the prepulses are of increasing amplitude, and the current measured is the differential of the current existing between each prepulse and pulse). With properly chosen DNPV parameters, the response to glucose presented a peak at a potential of about 1 V versus an Ag/AgC1-reference, owing to the oxidation of enzymatically produced hydrogen peroxide. The calibration curves obtained (peak height/glucose concentration) were linear from 0.3-0.5 up to 1.5-6.5 mM and showed a sensitivity ranging from 1.4 up to 34.5 mA M-1 cm-2, depending on the sensor type. The DNPV response to glucose exhibited an essential insensitivity toward easily oxidizable interfering substances such as ascorbic acid and acetaminophen present at physiological concentrations. Peptides, the interfering species typical of the cerebral medium, were effectively retained by the above additional membranes. Concentration values of glucose in plasma and cerebrospinal fluid, determined in vitro from the DNPV peak height, agreed well with those measured by standard procedures. In the anesthetized rat, extracellular brain concentration of glucose was also monitored during administration of either insulin or glucagon. Under such pharmacological conditions, the changes observed in the peak height were in perfect agreement with the known effects induced by both substances.

  13. Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study.

    PubMed

    Zhu, Yihong; Gao, Bin; Hua, Jianming; Liu, Weibo; Deng, Yichao; Zhang, Lijie; Jiang, Biao; Zang, Yufeng

    2013-02-01

    Methylphenidate (MPH) is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder (ADHD). Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging (fMRI), few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication (20 mg MPH or placebo, order counterbalanced between participants). We demonstrated that: (1) there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; (2) the left middle and superior temporal gyri had stronger MPHrelated regional homogeneity (ReHo); and (3) the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.

  14. Prevalence of lateral ventricle asymmetry in brain MRI studies of neurologically normal dogs and dogs with idiopathic epilepsy.

    PubMed

    Pivetta, Mauro; De Risio, Luisa; Newton, Richard; Dennis, Ruth

    2013-01-01

    Asymmetry of the cerebral lateral ventricles is a common finding in cross-sectional imaging of otherwise normal canine brains and has been assumed to be incidental. The purpose of this retrospective study was to compare the prevalence of ventricular asymmetry in brain MRI studies of normal dogs and dogs with idiopathic epilepsy. Brain MRI archives were searched for 100 neurologically normal dogs (Group 1) and 100 dogs with idiopathic epilepsy (Group 2). For each dog, asymmetry of the lateral ventricles was subjectively classified as absent, mild, moderate, and severe based on a consensus of two observers who were unaware of group status. Ventricular areas were measured from transverse T1W images at the level of the interthalamic adhesion. An asymmetry ratio was calculated as the ratio of the larger to smaller ventricular transverse area. There was excellent agreement between subjective assessments of ventricular asymmetry and quantitative assessments using asymmetry ratios (k = 0.995). The prevalence of asymmetry was 38% in Group 1 dogs and 44% in Group 2 dogs. Assymmetry was scored as mild in the majority of Group 2 dogs. There was no significant association between presence/absence and degree of ventricular asymmetry vs. dog group, age, gender, or skull conformation. Findings from the current study supported previously published assumptions that asymmetry of the lateral cerebral ventricles is an incidental finding in MRI studies of the canine brain.

  15. Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and brain of mice following oocyte in vitro maturation but postnatal brain development and cognitive function are normal.

    PubMed

    Wang, Ning; Wang, Liya; Le, Fang; Zhan, Qitao; Zheng, Yingming; Ding, Guolian; Chen, Xijing; Sheng, Jianzhong; Dong, Minyue; Huang, Hefeng; Jin, Fan

    2011-09-01

    Despite the efforts to recapitulate the follicle environment, oocytes from in vitro maturation (IVM) have poorer developmental potential than those matured in vivo and the effects on the resultant offspring are of concern. The aim of this study was to determine altered gene expression in oocytes following IVM and to evaluate the expression of the arginine rich, mutated in early stage of tumors gene (Armet) and mitochondrial ribosomal protein L51 (Mrpl51) in embryos and brains of fetal/postnatal mice and the brain development of IVM offspring. An IVM mouse model was established while oocytes matured in vivo were used as the controls. Suppressive subtractive hybridization (SSH) and RT-PCR/western blot were used to analyze the differential expression of genes/proteins between IVM and the control group. HE staining and water maze were used to assess the histological changes in brain tissue and cognition of the offspring. The rates of fertilization, cleavage, and live birth were significantly decreased in IVM group. Thirteen genes were upregulated in IVM oocytes compared with the control, including Armet and Mrpl51. The higher level of Armet in IVM oocytes was retained in brain of newborn mice, which could be related to the upregulation of activating transcription factor 6 (Atf6) and X-box binding protein 1 (Xbp1), while Mrpl51 was expressed normally in brain of postnatal mice. No significant differences were detected in brain weight, neuronal counts, and the cognition in the offspring between the two groups. The present results suggested that IVM could affect the pregnancy outcome and the Armet and Mrpl51 gene/protein expression. The change in Armet expression lasted while the change of Mrpl51 disappeared after birth. However, the brain development of the offspring seemed to be unaffected by IVM.

  16. The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI).

    PubMed

    Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, M Okan; Botteron, Kelly N; McCracken, James; McKinstry, Robert C; Rivkin, Michael J; Wang, Dah-Jyuu; Rumsey, Judith; Pierpaoli, Carlo

    2016-01-01

    The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools. This paper focuses on the DTI component of the NIH MRI study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov. This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data.

  17. How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

    PubMed Central

    Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

    2015-01-01

    Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total

  18. Early Supplementation of Phospholipids and Gangliosides Affects Brain and Cognitive Development in Neonatal Piglets123

    PubMed Central

    Liu, Hongnan; Radlowski, Emily C; Conrad, Matthew S; Li, Yao; Dilger, Ryan N; Johnson, Rodney W

    2014-01-01

    Background: Because human breast milk is a rich source of phospholipids and gangliosides and breastfed infants have improved learning compared with formula-fed infants, the importance of dietary phospholipids and gangliosides for brain development is of interest. Objective: We sought to determine the effects of phospholipids and gangliosides on brain and cognitive development. Methods: Male and female piglets from multiple litters were artificially reared and fed formula containing 0% (control), 0.8%, or 2.5% Lacprodan PL-20 (PL-20; Arla Foods Ingredients), a phospholipid/ganglioside supplement, from postnatal day (PD) 2 to PD28. Beginning on PD14, performance in a spatial T-maze task was assessed. At PD28, brain MRI data were acquired and piglets were killed to obtain hippocampal tissue for metabolic profiling. Results: Diet affected maze performance, with piglets that were fed 0.8% and 2.5% PL-20 making fewer errors than control piglets (80% vs. 75% correct on average; P < 0.05) and taking less time to make a choice (3 vs. 5 s/trial; P < 0.01). Mean brain weight was 5% higher for piglets fed 0.8% and 2.5% PL-20 (P < 0.05) than control piglets, and voxel-based morphometry revealed multiple brain areas with greater volumes and more gray and white matter in piglets fed 0.8% and 2.5% PL-20 than in control piglets. Metabolic profiling of hippocampal tissue revealed that multiple phosphatidylcholine-related metabolites were altered by diet. Conclusion: In summary, dietary phospholipids and gangliosides improved spatial learning and affected brain growth and composition in neonatal piglets. PMID:25411030

  19. Affective Brain-Computer Interfaces As Enabling Technology for Responsive Psychiatric Stimulation

    PubMed Central

    Widge, Alik S.; Dougherty, Darin D.; Moritz, Chet T.

    2014-01-01

    There is a pressing clinical need for responsive neurostimulators, which sense a patient’s brain activity and deliver targeted electrical stimulation to suppress unwanted symptoms. This is particularly true in psychiatric illness, where symptoms can fluctuate throughout the day. Affective BCIs, which decode emotional experience from neural activity, are a candidate control signal for responsive stimulators targeting the limbic circuit. Present affective decoders, however, cannot yet distinguish pathologic from healthy emotional extremes. Indiscriminate stimulus delivery would reduce quality of life and may be actively harmful. We argue that the key to overcoming this limitation is to specifically decode volition, in particular the patient’s intention to experience emotional regulation. Those emotion-regulation signals already exist in prefrontal cortex (PFC), and could be extracted with relatively simple BCI algorithms. We describe preliminary data from an animal model of PFC-controlled limbic brain stimulation and discuss next steps for pre-clinical testing and possible translation. PMID:25580443

  20. Affective Brain-Computer Interfaces As Enabling Technology for Responsive Psychiatric Stimulation.

    PubMed

    Widge, Alik S; Dougherty, Darin D; Moritz, Chet T

    2014-04-01

    There is a pressing clinical need for responsive neurostimulators, which sense a patient's brain activity and deliver targeted electrical stimulation to suppress unwanted symptoms. This is particularly true in psychiatric illness, where symptoms can fluctuate throughout the day. Affective BCIs, which decode emotional experience from neural activity, are a candidate control signal for responsive stimulators targeting the limbic circuit. Present affective decoders, however, cannot yet distinguish pathologic from healthy emotional extremes. Indiscriminate stimulus delivery would reduce quality of life and may be actively harmful. We argue that the key to overcoming this limitation is to specifically decode volition, in particular the patient's intention to experience emotional regulation. Those emotion-regulation signals already exist in prefrontal cortex (PFC), and could be extracted with relatively simple BCI algorithms. We describe preliminary data from an animal model of PFC-controlled limbic brain stimulation and discuss next steps for pre-clinical testing and possible translation.

  1. Searching for Factors Underlying Cerebral Plasticity in the Normal and Injured Brain

    ERIC Educational Resources Information Center

    Kolb, Bryan; Muhammad, Arif; Gibb, Robbin

    2011-01-01

    Brain plasticity refers to the capacity of the nervous system to change its structure and ultimately its function over a lifetime. There have been major advances in our understanding of the principles of brain plasticity and behavior in laboratory animals and humans. Over the past decade there have been advances in the application of these…

  2. Transitory cystic cavities in the developing mammalian brain - normal or anomalous?

    PubMed

    Kaur, Charanjit; Ling, Eng-Ang

    2017-02-01

    Transitory cavities associated with the ventricular system represent probably one of the most unique features in the developing mammalian brain. In rodents, the cavities exist transiently in the developing brain and do not appear to be associated with any pathological events. Among the various cavities, the pyramidal-shaped cavum septum pellucidum (CSP) located beneath the corpus callosum and between the lateral ventricles is most well defined. In addition to the CSP are the bilateral subependymal cysts that are consistently associated with the third and fourth ventricles as well as the aqueduct. The cavities/cysts contain a large number of amoeboid microglia expressing surface receptors and hydrolytic enzymes common to tissue macrophages. The significance of these cavities in the developing brain remains a conjecture. Firstly, the cavity walls are free of an apparent epithelial lining; hence, it is speculated that the cavities that appear to communicate with the widened neighboring interstitial tissue spaces may have resulted from physical traction due to the rapid growth of the perinatal brain. Secondly, the cavities contain prominent clusters of amoeboid microglia that may be involved in clearing the debris of degenerating axons and cells resulting from the early brain tissue remodeling. With the increase in brain tissue compactness following the beginning of myelination in the second postnatal week, all cavities are obliterated; concomitantly, the number of amoeboid microglia in them diminishes and all this might signal further maturation of the brain.

  3. Diffusional anisotropy of the human brain assessed with diffusion-weighted MR: Relation with normal brain development and aging

    SciTech Connect

    Nomura, Toshiyuki; Sakuma, Hajime; Takeda, Kan; Tagami, Tomoyasu; Okuda, Yasuyuki; Nakagawa, Tsuyoshi )

    1994-02-01

    To analyze diffusional anisotropy in frontal and occipital white matter of human brain quantitatively as a function of age by using diffusion-weighted MR imaging. Ten neonates (<1 month), 13 infants (1-10 months), 9 children (1-11 years), and 16 adults (20-79 years) were examined. After taking axial spin-echo images of the brain, diffusion-sensitive gradients were added parallel or perpendicular to the orientation of nerve fibers. The apparent diffusion coefficient parallel to the nerve fibers (0) and that perpendicular to the fibers (90) were computed. The anisotropic ratio (90/0) was calculated as a function of age. Anisotropic ratios of frontal white matter were significantly larger in neonates as compared with infants, children, or adults. The ratios showed rapid decrease until 6 months and thereafter were identical in all subjects. In the occipital lobe, the ratios were also greater in neonates, but the differences from other age groups were not so prominent as in the frontal lobe. Comparing anisotropic ratios between frontal and occipital lobes, a significant difference was observed only in neonates. Diffusion-weighted images demonstrated that the myelination process starts earlier in the occipital lobe than in the frontal lobe. The changes of diffusional anisotropy in white matter are completed within 6 months after birth. Diffusion-weighted imaging provides earlier detection of brain myelination compared with the conventional T1- and T2-weighted images. 18 refs., 6 figs., 1 tab.

  4. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

  5. A Double Blind Trial of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain Injury

    DTIC Science & Technology

    2016-01-01

    Award Number: W81XWH-08-2-0652 TITLE: A Double Blind Trial of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain...of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain Injury 5b. GRANT NUMBER PT075168 5c. PROGRAM ELEMENT...expressed as affective lability, will decrease significantly in TBI subjects treated with divalproex sodium , a mood stabilizing medication, as

  6. Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

    NASA Astrophysics Data System (ADS)

    Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

    2014-03-01

    Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

  7. Factors Affecting the Normalization of CALL in Chinese Senior High Schools

    ERIC Educational Resources Information Center

    He, Bi; Puakpong, Nattaya; Lian, Andrew

    2015-01-01

    With the development of Information Technology, increasing attention has been paid to Computer Assisted Language Learning (CALL). Meanwhile, increasing enthusiasm is seen for English learning and teaching in China. Yet, few research studies have focused on the normalization of CALL in ethnically diverse areas. In response to this research gap,…

  8. Polyphenol oxidase affects normal nodule development in red clover (Trifolium pratense L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyphenol oxidase (PPO) may have multiple functions in tissues, depending on its cellular or tissue localization. We used PPO RNAi transformants of red clover (Trifolium pratense) to determine the role PPO plays in normal development of plants, and especially in nitrogen-fixing nodules. In red clov...

  9. The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimer's disease brain.

    PubMed

    Stockley, J H; O'Neill, C

    2007-06-01

    The insidious progression of AD (Alzheimer's disease) is believed to be linked closely to the production, accumulation and aggregation of the approximately 4.5 kDa protein fragment called Abeta (amyloid beta-peptide). Abeta is produced by sequential cleavage of the amyloid precursor protein by two enzymes referred to as beta- and gamma-secretase. beta-Secretase is of central importance, as it catalyses the rate-limiting step in the production of Abeta and was identified 7 years ago as BACE1 (beta-site APP-cleaving enzyme 1). Soon afterwards, its homologue BACE2 was discovered, and both proteins represent a new subclass of the aspartyl protease family. Studies examining the regulation and function of beta-secretase in the normal and AD brain are central to the understanding of excessive production of Abeta in AD, and in targeting and normalizing this beta-secretase process if it has gone awry in the disease. Several reports indicate this, showing increased beta-secretase activity in AD, with recent findings by our group showing changes in beta-secretase enzyme kinetics in AD brain caused by an increased V(max). This article gives a brief review of studies which have examined BACE1 protein levels and beta-secretase activity in control and AD brain, considering further the expression of BACE2 in the human brain.

  10. Prenatal caffeine intake differently affects synaptic proteins during fetal brain development.

    PubMed

    Mioranzza, Sabrina; Nunes, Fernanda; Marques, Daniela M; Fioreze, Gabriela T; Rocha, Andréia S; Botton, Paulo Henrique S; Costa, Marcelo S; Porciúncula, Lisiane O

    2014-08-01

    Caffeine is the psychostimulant most consumed worldwide. However, little is known about its effects during fetal brain development. In this study, adult female Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the active cycle in weekdays, two weeks before mating and throughout pregnancy. Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20, respectively) were collected for immunodetection of the following synaptic proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein 25 (SNAP-25). Besides, the estimation of NeuN-stained nuclei (mature neurons) and non-neuronal nuclei was verified in both brain regions and embryonic periods. Caffeine (1.0 g/L) decreased the body weight of embryos at E20. Cortical BDNF at E18 was decreased by caffeine (1.0 g/L), while it increased at E20, with no major effects on TrkB receptors. In the hippocampus, caffeine decreased TrkB receptor only at E18, with no effects on BDNF. Moderate and high doses of caffeine promoted an increase in Shh in both brain regions at E18, and in the hippocampus at E20. Caffeine (0.3g/L) decreased GAP-43 only in the hippocampus at E18. The NeuN-stained nuclei increased in the cortex at E20 by lower dose and in the hippocampus at E18 by moderate dose. Our data revealed that caffeine transitorily affect synaptic proteins during fetal brain development. The increased number of NeuN-stained nuclei by prenatal caffeine suggests a possible acceleration of the telencephalon maturation. Although some modifications in the synaptic proteins were transient, our data suggest that caffeine even in lower doses may alter the fetal brain development.

  11. Comparing Cognitive Failures and Metacognitive Beliefs in Mild Traumatic Brain Injured Patients and Normal Controls in Kashan

    PubMed Central

    Zargar, Fatemeh; Mohammadi, Abolfazl; Shafiei, Elham; Fakharian, Esmaeil

    2015-01-01

    Background: Head trauma is associated with multiple destructive cognitive symptoms and cognitive failure. Cognitive failures include problems with memory, attention and operation. Cognitive failures are considered as a process associated with metacognition. Objectives: This study aimed to compare cognitive failures and metacognitive beliefs in mild Traumatic Brain Injured (TBI) patients and normal controls in Kashan. Patients and Methods: The study was performed on 40 TBI patients referred to the Shahid Beheshti Hospital of Kashan city and 40 normal controls in Kashan. Traumatic brain injured patients and normal controls were selected by convenience sampling. Two groups filled out the demographic sheet, Cognitive Failures Questionnaire (CFQ) and Meta-Cognitions Questionnaire 30 (MCQ-30). The data were analyzed by the SPSS-19 software with multivariate analysis of variance. Results: The results of this study showed that there were no significant differences between TBI and controls in total scores and subscales of CFQ and MCQ (F = 0.801, P = 0.61). Conclusions: Based on these findings, it seems that mild brain injuries don't make significant metacognitive problems and cognitive failures. PMID:26101761

  12. Detection of normal aging effects on human brain metabolite concentrations and microstructure with whole brain MR spectroscopic imaging and quantitative MR imaging

    PubMed Central

    Eylers, Vanessa V.; Maudsley, Andrew A.; Bronzlik, Paul; Dellani, Paulo R.; Lanfermann, Heinrich; Ding, Xiao-Qi

    2015-01-01

    Background and purpose Whole brain 1H-MR spectroscopic imaging (wbMRSI) was used in combination with quantitative MRI (qMRI) to study the effects of normal aging on healthy human brain metabolites and microstructure. Materials and Methods Sixty healthy volunteers aged 21 to 70 years were studied. Brain maps of the metabolites NAA, Cr, and Cho, and the tissue irreversible and reversible transverse relaxation times, T2 and T2′, were derived from the datasets. The relative metabolite concentrations [NAA], [tCr] and [Cho] as well as the values of relaxation times were measured with ROIs placed within frontal and parietal WM, centrum semiovale (CSO), splenium of the corpus callosum (SCC), hand motor area (HK), occipital GM, putamen, thalamus, pons ventral/dorsal (BSv/BSd), cerebellar white matter (CbWM) and posterior lobe (CbGM). Linear regression analysis and Pearson’s correlation tests were used to analyze the data. Results Aging resulted in decreased [NAA] in occipital GM, putamen, SCC, and BSv, and decreased [tCr] in BSd and putamen. [Cho] did not change significantly in selected brain regions. T2 increased in CbWM and decreased in SCC with aging, while the T2′ decreased in the occipital GM, HK, putamen, and increased in the SCC. Correlations were found between [NAA] and T2′ in occipital GM and putamen and between [tCr] and T2′ in the putamen. Conclusion The effects of normal aging on brain metabolites and microstructure are regional dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. PMID:26564440

  13. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-05

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  14. Evaluating ambivalence: social-cognitive and affective brain regions associated with ambivalent decision-making.

    PubMed

    Nohlen, Hannah U; van Harreveld, Frenk; Rotteveel, Mark; Lelieveld, Gert-Jan; Crone, Eveline A

    2014-07-01

    Ambivalence is a state of inconsistency that is often experienced as affectively aversive. In this functional magnetic resonance imaging study, we investigated the role of cognitive and social-affective processes in the experience of ambivalence and coping with its negative consequences. We examined participants' brain activity during the dichotomous evaluation (pro vs contra) of pretested ambivalent (e.g. alcohol), positive (e.g. happiness) and negative (e.g. genocide) word stimuli. We manipulated evaluation relevance by varying the probability of evaluation consequences, under the hypothesis that ambivalence is experienced as more negative when outcomes are relevant. When making ambivalent evaluations, more activity was found in the anterior cingulate cortex, the insula, the temporal parietal junction (TPJ) and the posterior cingulate cortex (PCC)/precuneus, for both high and low evaluation relevance. After statistically conservative corrections, activity in the TPJ and PCC/precuneus was negatively correlated with experienced ambivalence after scanning, as measured by Priester and Petty's felt ambivalence scale (1996). The findings show that cognitive and social-affective brain areas are involved in the experience of ambivalence. However, these networks are differently associated with subsequent reduction of ambivalence, thus highlighting the importance of understanding both cognitive and affective processes involved in ambivalent decision-making.

  15. Linear and nonlinear analysis of normal and CAD-affected heart rate signals.

    PubMed

    Acharya, U Rajendra; Faust, Oliver; Sree, Vinitha; Swapna, G; Martis, Roshan Joy; Kadri, Nahrizul Adib; Suri, Jasjit S

    2014-01-01

    Coronary artery disease (CAD) is one of the dangerous cardiac disease, often may lead to sudden cardiac death. It is difficult to diagnose CAD by manual inspection of electrocardiogram (ECG) signals. To automate this detection task, in this study, we extracted the heart rate (HR) from the ECG signals and used them as base signal for further analysis. We then analyzed the HR signals of both normal and CAD subjects using (i) time domain, (ii) frequency domain and (iii) nonlinear techniques. The following are the nonlinear methods that were used in this work: Poincare plots, Recurrence Quantification Analysis (RQA) parameters, Shannon entropy, Approximate Entropy (ApEn), Sample Entropy (SampEn), Higher Order Spectra (HOS) methods, Detrended Fluctuation Analysis (DFA), Empirical Mode Decomposition (EMD), Cumulants, and Correlation Dimension. As a result of the analysis, we present unique recurrence, Poincare and HOS plots for normal and CAD subjects. We have also observed significant variations in the range of these features with respect to normal and CAD classes, and have presented the same in this paper. We found that the RQA parameters were higher for CAD subjects indicating more rhythm. Since the activity of CAD subjects is less, similar signal patterns repeat more frequently compared to the normal subjects. The entropy based parameters, ApEn and SampEn, are lower for CAD subjects indicating lower entropy (less activity due to impairment) for CAD. Almost all HOS parameters showed higher values for the CAD group, indicating the presence of higher frequency content in the CAD signals. Thus, our study provides a deep insight into how such nonlinear features could be exploited to effectively and reliably detect the presence of CAD.

  16. Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans.

    PubMed Central

    Boyle, P J; Scott, J C; Krentz, A J; Nagy, R J; Comstock, E; Hoffman, C

    1994-01-01

    Systemic glucose utilization declines during sleep in man. We tested the hypothesis that this decline in utilization is largely accounted for by reduced brain glucose metabolism. 10 normal subjects underwent internal jugular and radial artery cannulation to determine cerebral blood flow by N2O equilibrium technique and to quantitate cross-brain glucose and oxygen differences before and every 3 h during sleep. Sleep stage was graded by continuous electroencephalogram, and systemic glucose turnover was estimated by isotope dilution. Brain glucose metabolism fell from 33.6 +/- 2.2 mumol/100 g per min (mean +/- SE) before sleep (2300 h) to a mean nadir of 24.3 +/- 1.1 mumol/100 g per min at 0300 h during sleep (P = 0.001). Corresponding rates of systemic glucose utilization fell from 13.2 +/- 0.8 to 11.0 +/- 0.5 mumol/kg per min (P = 0.003). Diminished brain glucose metabolism was the product of a reduced arteriovenous glucose difference, 0.643 +/- 0.024 to 0.546 +/- 0.020 mmol/liter (P = 0.002), and cerebral blood flow, 50.3 +/- 2.8 to 44.6 +/- 1.4 cc/100 g per min (P = 0.021). Brain oxygen metabolism fell commensurately from 153.4 +/- 11.8 to 128.0 +/- 8.4 mumol/100 g per min (P = 0.045). The observed reduction in brain metabolism occurred independent of stage of central nervous system electrical activity (electroencephalographic data), and was more closely linked to duration of sleep. We conclude that a decline in brain glucose metabolism is a significant determinant of falling rates of systemic glucose utilization during sleep. Images PMID:8113391

  17. Factors affecting post-stroke motor recovery: Implications on neurotherapy after brain injury.

    PubMed

    Alawieh, Ali; Zhao, Jing; Feng, Wuwei

    2016-08-13

    Neurological disorders are a major cause of chronic disability globally among which stroke is a leading cause of chronic disability. The advances in the medical management of stroke patients over the past decade have significantly reduced mortality, but at the same time increased numbers of disabled survivors. Unfortunately, this reduction in mortality was not paralleled by satisfactory therapeutics and rehabilitation strategies that can improve functional recovery of patients. Motor recovery after brain injury is a complex, dynamic, and multifactorial process in which an interplay among genetic, pathophysiologic, sociodemographic and therapeutic factors determines the overall recovery trajectory. Although stroke recovery is the most well-studied form of post-injury neuronal recovery, a thorough understanding of the pathophysiology and determinants affecting stroke recovery is still lacking. Understanding the different variables affecting brain recovery after stroke will not only provide an opportunity to develop therapeutic interventions but also allow for developing personalized platforms for patient stratification and prognosis. We aim to provide a narrative review of major determinants for post-stroke recovery and their implications in other forms of brain injury.

  18. The roles of the amygdala in the affective regulation of body, brain, and behaviour

    NASA Astrophysics Data System (ADS)

    Mirolli, Marco; Mannella, Francesco; Baldassarre, Gianluca

    2010-09-01

    Despite the great amount of knowledge produced by the neuroscientific literature on affective phenomena, current models tackling non-cognitive aspects of behaviour are often bio-inspired but rarely bio-constrained. This paper presents a theoretical account of affective systems centred on the amygdala (Amg). This account aims to furnish a general framework and specific pathways to implement models that are more closely related to biological evidence. The Amg, which receives input from brain areas encoding internal states, innately relevant stimuli, and innately neutral stimuli, plays a fundamental role in the motivational and emotional processes of organisms. This role is based on the fact that Amg implements the two associative processes at the core of Pavlovian learning (conditioned stimulus (CS)-unconditioned stimulus (US) and CS-unconditioned response (UR) associations), and that it has the capacity of modulating these associations on the basis of internal states. These functionalities allow the Amg to play an important role in the regulation of the three fundamental classes of affective responses (namely, the regulation of body states, the regulation of brain states via neuromodulators, and the triggering of a number of basic behaviours fundamental for adaptation) and in the regulation of three high-level cognitive processes (namely, the affective labelling of memories, the production of goal-directed behaviours, and the performance of planning and complex decision-making). Our analysis is conducted within a methodological approach that stresses the importance of understanding the brain within an evolutionary/adaptive framework and with the aim of isolating general principles that can potentially account for the wider possible empirical evidence in a coherent fashion.

  19. Relationship between Defenses, Personality, and Affect during a Stress Task in Normal Adolescents

    ERIC Educational Resources Information Center

    Steiner, Hans; Erickson, Sarah J.; MacLean, Peggy; Medic, Sanja; Plattner, Belinda; Koopman, Cheryl

    2007-01-01

    Objective: Although there are extensive data on the relationship between personality and stress reactivity in adults, there is little comparable empirical research with adolescents. This study examines the simultaneous relationships between long term functioning (personality, defenses) and observed stress reactivity (affect) in adolescents.…

  20. Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking

    PubMed Central

    Wang, Haifeng; Wen, Baohong; Cheng, Jingliang; Li, Hongpeng

    2017-01-01

    In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations. PMID:28091559

  1. Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking.

    PubMed

    Wang, Haifeng; Wen, Baohong; Cheng, Jingliang; Li, Hongpeng

    2017-01-16

    In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations.

  2. Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions.

    PubMed

    Ueno, Masaki; Chiba, Yoichi; Murakami, Ryuta; Matsumoto, Koichi; Kawauchi, Machi; Fujihara, Ryuji

    2016-04-01

    Blood-borne substances can invade into the extracellular spaces of the brain via endothelial cells in sites without the blood-brain barrier (BBB), and can travel through the interstitial fluid (ISF) of the brain parenchyma adjacent to non-BBB sites. It has been shown that cerebrospinal fluid (CSF) drains directly into the blood via the arachnoid villi and also into lymph nodes via the subarachnoid spaces of the brain, while ISF drains into the cervical lymph nodes through perivascular drainage pathways. In addition, the glymphatic pathway of fluids, characterized by para-arterial pathways, aquaporin4-dependent passage through astroglial cytoplasm, interstitial spaces, and paravenous routes, has been established. Meningeal lymphatic vessels along the superior sagittal sinus were very recently discovered. It is known that, in mice, blood-borne substances can be transferred to areas with intact BBB function, such as the medial regions of the hippocampus, presumably through leaky vessels in non-BBB sites. In the present paper, we review the clearance mechanisms of interstitial substances, such as amyloid-β peptides, as well as summarize models of BBB deterioration in response to different types of insults, including acute ischemia followed by reperfusion, hypertension, and chronic hypoperfusion. Lastly, we discuss the relationship between perivascular clearance and brain disorders.

  3. Dyrk1A Haploinsufficiency Affects Viability and Causes Developmental Delay and Abnormal Brain Morphology in Mice

    PubMed Central

    Fotaki, Vassiliki; Dierssen, Mara; Alcántara, Soledad; Martínez, Salvador; Martí, Eulàlia; Casas, Caty; Visa, Joana; Soriano, Eduardo; Estivill, Xavier; Arbonés, Maria L.

    2002-01-01

    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, we have generated mice deficient in Dyrk1A function by gene targeting. Dyrk1A−/− null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/−) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/− mice and specific alterations in adults. Brains of Dyrk1A+/− mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies. PMID:12192061

  4. The Importance of Vocal Affect to Bimodal Processing of Emotion: Implications for Individuals with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Zupan, Barbra; Neumann, Dawn; Babbage, Duncan R.; Willer, Barry

    2009-01-01

    Persons with traumatic brain injury (TBI) often have difficulty recognizing emotion in others. This is likely due to difficulties in interpreting non-verbal cues of affect. Although deficits in interpreting facial cues of affect are being widely explored, interpretation of vocal cues of affect has received much less attention. Accurate…

  5. Acidity and Acid-Sensing Ion Channels in the Normal and Alzheimer's Disease Brain.

    PubMed

    Gonzales, Eric B; Sumien, Nathalie

    2017-02-15

    Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain. We will also cover the pathophysiological associations between ASICs and modulators of ASICs. Finally, this review will sum up how the studies of protons, ASICs and their modulators may generate new therapeutic molecules for Alzheimer's disease and other neurodegenerative diseases.

  6. Co-localization of brain-derived neurotrophic factor (BDNF) and wild-type huntingtin in normal and quinolinic acid-lesioned rat brain.

    PubMed

    Fusco, Francesca R; Zuccato, Chiara; Tartari, Marzia; Martorana, Alessandro; De March, Zena; Giampà, Carmela; Cattaneo, Elena; Bernardi, Giorgio

    2003-09-01

    Loss of huntingtin-mediated brain-derived neurotrophic factor (BDNF) gene transcription has been described in Huntington's disease (HD) [Zuccato et al. (2001) Science, 293, 493-498]. It has been shown that BDNF is synthesized in the pyramidal layer of cerebral cortex and released in the striatum [Altar et al. (1997) Nature, 389, 856-860; Conner et al. (1997) J. Neurosci., 17, 2295-2313]. Here we show the cellular localization of BDNF in huntingtin-containing neurons in normal rat brain; our double-label immunofluorescence study shows that huntingtin and BDNF are co-contained in approximately 99% of pyramidal neurons of motor cortex. In the striatum, huntingtin is expressed in 75% of neurons containing BDNF. In normal striatum we also show that BDNF is contained in cholinergic and in NOS-containing interneurons, which are relatively resistant to HD degeneration. Furthermore, we show a reduction in huntingtin and in BDNF immunoreactivity in cortical neurons after striatal excitotoxic lesion. Our data are confirmed by an ELISA study of BDNF and by a Western blot analysis of huntingtin in cortex of quinolic acid (QUIN)-lesioned hemispheres. In the lesioned striatum we describe that the striatal subpopulation of cholinergic neurons, surviving degeneration, contain BDNF. The finding that BDNF is contained in nearly all neurons that contain huntingtin in the normal cortex, along with the reduced expression of BDNF after QUIN injection of the striatum, shows that huntingtin may be required for BDNF production in cortex.

  7. Towards Tunable Consensus Clustering for Studying Functional Brain Connectivity During Affective Processing.

    PubMed

    Liu, Chao; Abu-Jamous, Basel; Brattico, Elvira; Nandi, Asoke K

    2017-03-01

    In the past decades, neuroimaging of humans has gained a position of status within neuroscience, and data-driven approaches and functional connectivity analyses of functional magnetic resonance imaging (fMRI) data are increasingly favored to depict the complex architecture of human brains. However, the reliability of these findings is jeopardized by too many analysis methods and sometimes too few samples used, which leads to discord among researchers. We propose a tunable consensus clustering paradigm that aims at overcoming the clustering methods selection problem as well as reliability issues in neuroimaging by means of first applying several analysis methods (three in this study) on multiple datasets and then integrating the clustering results. To validate the method, we applied it to a complex fMRI experiment involving affective processing of hundreds of music clips. We found that brain structures related to visual, reward, and auditory processing have intrinsic spatial patterns of coherent neuroactivity during affective processing. The comparisons between the results obtained from our method and those from each individual clustering algorithm demonstrate that our paradigm has notable advantages over traditional single clustering algorithms in being able to evidence robust connectivity patterns even with complex neuroimaging data involving a variety of stimuli and affective evaluations of them. The consensus clustering method is implemented in the R package "UNCLES" available on http://cran.r-project.org/web/packages/UNCLES/index.html .

  8. Functional connectivity in the resting brain as biological correlate of the Affective Neuroscience Personality Scales.

    PubMed

    Deris, Nadja; Montag, Christian; Reuter, Martin; Weber, Bernd; Markett, Sebastian

    2017-02-15

    According to Jaak Panksepp's Affective Neuroscience Theory and the derived self-report measure, the Affective Neuroscience Personality Scales (ANPS), differences in the responsiveness of primary emotional systems form the basis of human personality. In order to investigate neuronal correlates of personality, the underlying neuronal circuits of the primary emotional systems were analyzed in the present fMRI-study by associating the ANPS to functional connectivity in the resting brain. N=120 healthy participants were invited for the present study. The results were reinvestigated in an independent, smaller sample of N=52 participants. A seed-based whole brain approach was conducted with seed-regions bilaterally in the basolateral and superficial amygdalae. The selection of seed-regions was based on meta-analytic data on affective processing and the Juelich histological atlas. Multiple regression analyses on the functional connectivity maps revealed associations with the SADNESS-scale in both samples. Functional resting-state connectivity between the left basolateral amygdala and a cluster in the postcentral gyrus, and between the right basolateral amygdala and clusters in the superior parietal lobe and subgyral in the parietal lobe was associated with SADNESS. No other ANPS-scale revealed replicable results. The present findings give first insights into the neuronal basis of the SADNESS-scale of the ANPS and support the idea of underlying neuronal circuits. In combination with previous research on genetic associations of the ANPS functional resting-state connectivity is discussed as a possible endophenotype of personality.

  9. Stress shifts brain activation towards ventral 'affective' areas during emotional distraction.

    PubMed

    Oei, Nicole Y L; Veer, Ilya M; Wolf, Oliver T; Spinhoven, Philip; Rombouts, Serge A R B; Elzinga, Bernet M

    2012-04-01

    Acute stress has been shown to impair working memory (WM), and to decrease prefrontal activation during WM in healthy humans. Stress also enhances amygdala responses towards emotional stimuli. Stress might thus be specifically detrimental to WM when one is distracted by emotional stimuli. Usually, emotional stimuli presented as distracters in a WM task slow down performance, while evoking more activation in ventral 'affective' brain areas, and a relative deactivation in dorsal 'executive' areas. We hypothesized that after acute social stress, this reciprocal dorsal-ventral pattern would be shifted towards greater increase of ventral 'affective' activation during emotional distraction, while impairing WM performance. To investigate this, 34 healthy men, randomly assigned to a social stress or control condition, performed a Sternberg WM task with emotional and neutral distracters inside an MRI scanner. Results showed that WM performance after stress tended to be slower during emotional distraction. Brain activations during emotional distraction was enhanced in ventral affective areas, while dorsal executive areas tended to show less deactivation after stress. These results suggest that acute stress shifts priority towards processing of emotionally significant stimuli, at the cost of WM performance.

  10. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

    PubMed Central

    Berretta, Regina; Moscato, Pablo

    2016-01-01

    Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD

  11. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    PubMed

    Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kawashima, Ryuta

    2010-12-08

    Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  12. Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

    SciTech Connect

    Andreev, Victor P.; Petyuk, Vladislav A.; Brewer, Heather M.; Karpievitch, Yuliya V.; Xie, Fang; Clarke, Jennifer; Camp, David; Smith, Richard D.; Lieberman, Andrew P.; Albin, Roger L.; Nawaz, Zafar; El Hokayem, Jimmy; Myers, Amanda J.

    2012-06-01

    Quantitative proteomics analysis of cortical samples of 10 Alzheimer’s disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (p-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death.

  13. Reelin Proteolysis Affects Signaling Related to Normal Synapse Function and Neurodegeneration

    PubMed Central

    Lussier, April L.; Weeber, Edwin J.; Rebeck, G. William

    2016-01-01

    Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer’s diseases (AD) tissues including cerebral spinal fluid (CSF), showing that levels of Reelin fragments are altered in AD compared to control. Potential key proteases involved in Reelin proteolysis have recently been defined, identifying processes that could be altered in neurodegeneration. Introduction of full-length Reelin and its proteolytic fragments into several mouse models of neurodegeneration and neuropsychiatric disorders quickly promote learning and memory. These findings support a role for Reelin in learning and memory and suggest further understanding of these processes are important to harness the potential of this pathway in treating cognitive symptoms in neuropsychiatric and neurodegenerative diseases. PMID:27065802

  14. Evaluation of normalized energy recovery (NER) in microbial fuel cells affected by reactor dimensions and substrates.

    PubMed

    Xiao, Li; Ge, Zheng; Kelly, Patrick; Zhang, Fei; He, Zhen

    2014-04-01

    The objective of this study is to provide an initial evaluation of normalized energy recovery (NER - a new parameter for presenting energy performance) in microbial fuel cells (MFCs) through investigation of the effects of reactor dimensions and anode substrates. Although the larger-size MFCs generally have lower maximum power densities, their maximum NER is comparable to that of the smaller MFCs at the same anolyte flow rate. The mixed messages obtained from the MFC size tests suggest that MFCs can be further scaled up without decreasing energy recovery under certain conditions. The low-strength substrates seem to be more suitable for MFC treatment of wastewater, in terms of both energy recovery and organic removal. However, because the MFCs could not achieve the maximum NER and the maximum organic removal efficiency at the same time, one must determine a major goal for MFCs treating wastewater between energy recovery and contaminant removal.

  15. Predicting acute affective symptoms after deep brain stimulation surgery in Parkinson's disease.

    PubMed

    Schneider, Frank; Reske, Martina; Finkelmeyer, Andreas; Wojtecki, Lars; Timmermann, Lars; Brosig, Timo; Backes, Volker; Amir-Manavi, Atoosa; Sturm, Volker; Habel, Ute; Schnitzler, Alfons

    2010-01-01

    The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinson's disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.

  16. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury.

    PubMed

    Williamson, John; Isaki, Emi

    2015-01-01

    The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI). The modified FAR training was administered via telepractice to target social communication skills. Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play. Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication. Both participants with chronic TBI showed gains on identifying facial emotions on the static photos.

  17. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

    PubMed Central

    WILLIAMSON, JOHN; ISAKI, EMI

    2015-01-01

    The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI). The modified FAR training was administered via telepractice to target social communication skills. Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play. Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication. Both participants with chronic TBI showed gains on identifying facial emotions on the static photos. PMID:27563379

  18. Neither cimetidine nor probenecid affect the pharmacokinetics of tenoxicam in normal volunteers.

    PubMed Central

    Day, R O; Geisslinger, G; Paull, P; Williams, K M

    1994-01-01

    The effect of pretreatment with cimetidine (1 g day-1, 7 days) and of probenecid (1 g twice daily, 4 days) on the pharmacokinetics of tenoxicam (single oral dose, 20 mg) was studied in six healthy volunteers. Cmax was increased significantly when tenoxicam was given with probenecid (2.8 micrograms ml-1 alone, 3.5 micrograms ml-1 after probenecid; P < 0.005). No other pharmacokinetic parameters were altered significantly by either drug. It is concluded that neither cimetidine nor probenecid affects the pharmacokinetics of tenoxicam in a clinically important way. PMID:8148224

  19. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  20. Repeated electrical stimulation of reward-related brain regions affects cocaine but not "natural" reinforcement.

    PubMed

    Levy, Dino; Shabat-Simon, Maytal; Shalev, Uri; Barnea-Ygael, Noam; Cooper, Ayelet; Zangen, Abraham

    2007-12-19

    Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction.

  1. How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1.

    PubMed

    Serra, Laura; Petrucci, Antonio; Spanò, Barbara; Torso, Mario; Olivito, Giusy; Lispi, Ludovico; Costanzi-Porrini, Sandro; Giulietti, Giovanni; Koch, Giacomo; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1 matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tractbased spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1.

  2. Reconciling cognitive and affective neuroscience perspectives on the brain basis of emotional experience.

    PubMed

    Panksepp, Jaak; Lane, Richard D; Solms, Mark; Smith, Ryan

    2016-09-15

    The "affective" and "cognitive" neuroscience approaches to understanding emotion (AN and CN, respectively) represent potentially synergistic, but as yet unreconciled, theoretical perspectives, which may in part stem from the methods that these distinct perspectives routinely employ-one focusing on animal brain emotional systems (AN) and one on diverse human experimental approaches (CN). Here we present an exchange in which each approach (1) describes its own theoretical perspective, (2) offers a critique of the other perspective, and then (3) responds to each other's critique. We end with a summary of points of agreement and disagreement, and describe possible future experiments that could help resolve the remaining controversies. Future work should (i) further characterize the structure/function of subcortical circuitry with respect to its role in generating emotion, and (ii) further investigate whether sub-neocortical activations alone are sufficient (as opposed to merely necessary) for affective experiences, or whether subsequent cortical representation of an emotional response is also required.

  3. Social brain development and the affective consequences of ostracism in adolescence.

    PubMed

    Sebastian, Catherine; Viding, Essi; Williams, Kipling D; Blakemore, Sarah-Jayne

    2010-02-01

    Recent structural and functional imaging studies have provided evidence for continued development of brain regions involved in social cognition during adolescence. In this paper, we review this rapidly expanding area of neuroscience and describe models of neurocognitive development that have emerged recently. One implication of these models is that neural development underlies commonly observed adolescent phenomena such as susceptibility to peer influence and sensitivity to peer rejection. Experimental behavioural evidence of rejection sensitivity in adolescence is currently sparse. Here, we describe a study that directly compared the affective consequences of an experimental ostracism manipulation (Cyberball) in female adolescents and adults. The ostracism condition led to significantly greater affective consequences in the adolescents compared with adults. This suggests that the ability to regulate distress resulting from ostracism continues to develop between adolescence and adulthood. The results are discussed in the context of models of neurocognitive development.

  4. Polyphenol oxidase affects normal nodule development in red clover (Trifolium pratense L.)

    PubMed Central

    Webb, K. Judith; Cookson, Alan; Allison, Gordon; Sullivan, Michael L.; Winters, Ana L.

    2014-01-01

    Polyphenol oxidase (PPO) may have multiple functions in tissues depending on its cellular or tissue localization. Here we use PPO RNAi transformants of red clover (Trifolium pratense) to determine the role PPO plays in normal development of plants, and especially in N2-fixing nodules. In red clover, PPO was not essential for either growth or nodule production, or for nodule function in plants grown under optimal, N-free conditions. However, absence of PPO resulted in a more reduced environment in all tissues, as measured by redox potential, and caused subtle developmental changes in nodules. Leaves and, to a lesser extent nodules, lacking PPO tended to accumulate phenolic compounds. A comparison of nodules of two representative contrasting clones by microscopy revealed that nodules lacking PPO were morphologically and anatomically subtly altered, and that phenolics accumulated in different cells and tissues. Developing nodules lacking PPO were longer, and there were more cell layers within the squashed cell layer (SCL), but the walls of these cells were less thickened and the cells were less squashed. Within the N2-fixing zone, bacteroids appeared more granular and were less tightly packed together, and were similar to developmentally compromised bacteroids elicited by catalase mutant rhizobia reported elsewhere. PMID:25566275

  5. Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

    NASA Technical Reports Server (NTRS)

    Glenny, R. W.; Robertson, H. T.; Hlastala, M. P.

    2000-01-01

    To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

  6. The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain

    PubMed Central

    Wright, Amanda; Vissel, Bryce

    2012-01-01

    α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are comprised of different combinations of GluA1–GluA4 (also known asGluR1–GluR4 and GluR-A to GluR-D) subunits. The GluA2 subunit is subject to RNA editing by the ADAR2 enzyme, which converts a codon for glutamine (Gln; Q), present in the GluA2 gene, to a codon for arginine (Arg; R) found in the mRNA. AMPA receptors are calcium (Ca2+)-permeable if they contain the unedited GluA2(Q) subunit or if they lack the GluA2 subunit. While most AMPA receptors in the brain contain the edited GluA2(R) subunit and are therefore Ca2+-impermeable, recent evidence suggests that Ca2+-permeable AMPA receptors are important in synaptic plasticity, learning, and disease. Strong evidence supports the notion that Ca2+-permeable AMPA receptors are usually GluA2-lacking AMPA receptors, with little evidence to date for a significant role of unedited GluA2 in normal brain function. However, recent detailed studies suggest that Ca2+-permeable AMPA receptors containing unedited GluA2 do in fact occur in neurons and can contribute to excitotoxic cell loss, even where it was previously thought that there was no unedited GluA2.This review provides an update on the role of GluA2 RNA editing in the healthy and diseased brain and summarizes recent insights into the mechanisms that control this process. We suggest that further studies of the role of unedited GluA2 in normal brain function and disease are warranted, and that GluA2 editing should be considered as a possible contributing factor when Ca2+-permeable AMPA receptors are observed. PMID:22514516

  7. Environmental enrichment lessens cognitive decline in APP23 mice without affecting brain sirtuin expression.

    PubMed

    Polito, Letizia; Chierchia, Armando; Tunesi, Marta; Bouybayoune, Ihssane; Kehoe, Patrick Gavin; Albani, Diego; Forloni, Gianluigi

    2014-01-01

    Environmental enrichment (EE) is a non-pharmacological intervention reported to counteract pathological signs in models of Alzheimer's disease (AD). We developed EE protocols in APP23 mice and evaluated how they influenced cognitive decline and brain amyloid-β (Aβ) burden. We also investigated the involvement of sirtuins (SIRTs) as a possible molecular mediator of EE, by assessing hippocampal and cortical mRNA and protein levels of the SIRT family members (SIRT1 to SIRT7). APP23 transgenic mice were moved to EE cages (TG-EEs) starting from 3 months of age. TG-EEs were compared to transgenic mice housed in standard cages (TG-SHs) and to wild-type littermates in the two housing conditions (WT-EEs and WT-SHs). At 7 months of age, all mice were tested for behavioral performance with Morris Water Maze (MWM) and visual novel Object Recognition Test (vORT). After a month, a group underwent biochemical analyses, while another group continued in the EE environment till 18 months of age, when Aβ plaque load was assessed. At 7 months, TG-SHs had impaired behavioral performance in MWM and vORT. In contrast, TG-EE mice had restored behavioral performance. At 8 months, EE did not affect AβPP expression or processing, Aβ40/42, pGlu-Aβ3-40/3-42, or Aβ oligomer level. The expression of two Aβ degrading enzymes (insulin degrading enzyme and neprilysin) was not modulated by EE. Brain sirtuin mRNA and protein levels were unchanged, while brain-derived neurotrophic factor expression increased after EE. Aβ deposition was attenuated in 18-month-old TG-EE mice, without apparent reduction of neuroinflammatory signs. We suggest that EE had a beneficial effect on cognitive performance and lessened long-term Aβ accumulation, but brain sirtuin expression was not modulated when cognitive impairment was restored.

  8. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults

    PubMed Central

    Su, Yun Yan; Liang, Xue; Schoepf, U. Joseph; Varga-Szemes, Akos; West, Henry C.; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

    2015-01-01

    Abstract To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging. Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests. There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05). APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect. PMID:26717353

  9. Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

    PubMed

    de Campos, Brunno Machado; Coan, Ana Carolina; Lin Yasuda, Clarissa; Casseb, Raphael Fernandes; Cendes, Fernando

    2016-09-01

    Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  10. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.

    PubMed

    Mc Mahon, Brenda; Andersen, Sofie B; Madsen, Martin K; Hjordt, Liv V; Hageman, Ida; Dam, Henrik; Svarer, Claus; da Cunha-Bang, Sofi; Baaré, William; Madsen, Jacob; Hasholt, Lis; Holst, Klaus; Frokjaer, Vibe G; Knudsen, Gitte M

    2016-05-01

    Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.

  11. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.

    PubMed

    Sharman, Matthew J; Kraemer, William J; Love, Dawn M; Avery, Neva G; Gómez, Ana L; Scheett, Timothy P; Volek, Jeff S

    2002-07-01

    Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.

  12. Affective responses after different intensities of exercise in patients with traumatic brain injury

    PubMed Central

    Rzezak, Patricia; Caxa, Luciana; Santolia, Patricia; Antunes, Hanna K. M.; Suriano, Italo; Tufik, Sérgio; de Mello, Marco T.

    2015-01-01

    Background: Patients with traumatic brain injury (TBI) usually have mood and anxiety symptoms secondary to their brain injury. Exercise may be a cost-effective intervention for the regulation of the affective responses of this population. However, there are no studies evaluating the effects of exercise or the optimal intensity of exercise for this clinical group. Methods: Twelve male patients with moderate or severe TBI [mean age of 31.83 and SD of 9.53] and 12 age- and gender-matched healthy volunteers [mean age of 30.58 and SD of 9.53] participated in two sessions of exercise of high and moderate-intensity. Anxiety and mood was evaluated, and subjective assessment of experience pre- and post-exercise was assessed. A mixed between and within-subjects general linear model (GLM) analysis was conducted to compare groups [TBI, control] over condition [baseline, session 1, session 2] allowing for group by condition interaction to be determined. Planned comparisons were also conducted to test study hypotheses. Results: Although no group by condition interaction was observed, planned comparisons indicated that baseline differences between patients and controls in anxiety (Cohens’ d = 1.80), tension (d = 1.31), depression (d = 1.18), anger (d = 1.08), confusion (d = 1.70), psychological distress (d = 1.28), and physical symptoms (d = 1.42) disappear after one session of exercise, independently of the intensity of exercise. Conclusion: A single-section of exercise, regardless of exercise intensity, had a positive effect on the affective responses of patients with TBI both by increasing positive valence feelings and decreasing negative ones. Exercise can be an easily accessible intervention that may alleviate depressive symptoms related to brain injury. PMID:26161074

  13. Provocative motion causes fall in brain temperature and affects sleep in rats.

    PubMed

    Del Vecchio, Flavia; Nalivaiko, Eugene; Cerri, Matteo; Luppi, Marco; Amici, Roberto

    2014-08-01

    Neural substrate of nausea is poorly understood, contrasting the wealth of knowledge about the emetic reflex. One of the reasons for this knowledge deficit is limited number and face validity of animal models of nausea. Our aim was to search for new physiological correlates of nausea in rats. Specifically, we addressed the question whether provocative motion (40-min rotation at 0.5 Hz) affects sleep architecture, brain temperature, heart rate (HR) and arterial pressure. Six adult male Sprague–Dawley rats were instrumented for recordings of EEG, nuchal electromyographic, hypothalamic temperature and arterial pressure. Provocative motion had the following effects: (1) total abolition of REM sleep during rotation and its substantial reduction during the first hour post-rotation (from 20 ± 3 to 5 ± 1.5%); (2) reduction in NREM sleep, both during rotation (from 57 ± 6 to 19 ± 5%) and during the first hour post-rotation (from 56 ± 3 to 41 ± 9%); (3) fall in the brain temperature (from 37.1 ± 0.1 to 36.0 ± 0.1 °C); and (4) reduction in HR (from 375 ± 6 to 327 ± 7 bpm); arterial pressure was not affected. Ondansetron, a 5-HT3 antagonist, had no major effect on all observed parameters during both baseline and provocative motion. We conclude that in rats, provocative motion causes prolonged arousing effects, however without evidence of sympathetic activation that usually accompanies heightened arousal. Motion induced fall in the brain temperature complements and extends our previous observations in rats and suggests that similar to humans, provocative motion triggers coordinated thermoregulatory response, leading to hypothermia in this species.

  14. Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains.

    PubMed

    Good, C D; Johnsrude, I; Ashburner, J; Henson, R N; Friston, K J; Frackowiak, R S

    2001-09-01

    We used voxel-based morphometry (VBM) to examine human brain asymmetry and the effects of sex and handedness on brain structure in 465 normal adults. We observed significant asymmetry of cerebral grey and white matter in the occipital, frontal, and temporal lobes (petalia), including Heschl's gyrus, planum temporale (PT) and the hippocampal formation. Males demonstrated increased leftward asymmetry within Heschl's gyrus and PT compared to females. There was no significant interaction between asymmetry and handedness and no main effect of handedness. There was a significant main effect of sex on brain morphology, even after accounting for the larger global volumes of grey and white matter in males. Females had increased grey matter volume adjacent to the depths of both central sulci and the left superior temporal sulcus, in right Heschl's gyrus and PT, in right inferior frontal and frontomarginal gyri and in the cingulate gyrus. Females had significantly increased grey matter concentration extensively and relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the banks of the cingulate and calcarine sulci. Males had increased grey matter volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal cortex, and in the anterior lobes of the cerebellum, but no regions of increased grey matter concentration.

  15. The affective and cognitive processing of touch, oral texture, and temperature in the brain.

    PubMed

    Rolls, Edmund T

    2010-02-01

    Some of the principles of the representation of affective touch in the brain are described. Positively affective touch and temperature are represented in parts of the orbitofrontal and pregenual cingulate cortex. The orbitofrontal cortex is implicated in some of the affective aspects of touch that may be mediated through C fibre touch afferents, in that it is activated more by light touch to the forearm (a source of C-tactile (CT) afferents) than by light touch to the glabrous skin of the hand. Oral somatosensory afferents implicated in sensing the texture of food including fat in the mouth also activate the orbitofrontal and pregenual cingulate cortex, as well as the insular taste cortex. Top-down cognitive modulation of the representation of affective touch produced by word labels is found in parietal cortex area 7, the insula and ventral striatum. The cognitive labels also influence activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum.

  16. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    PubMed

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  17. Developmental Component in Brain Electrical Activity of Normal and Learning Disabled Boys.

    ERIC Educational Resources Information Center

    Naour, Paul J.; Martin, Daniel J.

    The study examined the electrophysiologic organization of cognitive function in 12 normally achieving righthanded boys and 12 reading disabled third and sixth grade boys. Ss were administered reading comprehension and spelling recognition subtests from the Peabody Individual Achievement Test. Electroencephalography (EEG) scores were recorded for…

  18. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

    PubMed

    Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

    2014-03-01

    Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

  19. Systemic Delivery of a Brain-Penetrant TrkB Antagonist Reduces Cocaine Self-Administration and Normalizes TrkB Signaling in the Nucleus Accumbens and Prefrontal Cortex

    PubMed Central

    Vendruscolo, Leandro F.; Caffino, Lucia; Giannotti, Giuseppe; Cazorla, Maxime; Fumagalli, Fabio; Riva, Marco A.; Homberg, Judith R.; Koob, George F.; Contet, Candice

    2016-01-01

    Cocaine exposure alters brain-derived neurotrophic factor (BDNF) expression in the brain. BDNF signaling through TrkB receptors differentially modulates cocaine self-administration, depending on the brain regions involved. In the present study, we determined how brain-wide inhibition of TrkB signaling affects cocaine intake, the motivation for the drug, and reinstatement of drug taking after extinction. To overcome the inability of TrkB ligands to cross the blood–brain barrier, the TrkB antagonist cyclotraxin-B was fused to the nontoxic transduction domain of the tat protein from human immunodeficiency virus type 1 (tat-cyclotraxin-B). Intravenous injection of tat-cyclotraxin-B dose-dependently reduced cocaine intake, motivation for cocaine (as measured under a progressive ratio schedule of reinforcement), and reinstatement of cocaine taking in rats allowed either short or long access to cocaine self-administration. In contrast, the treatment did not affect operant responding for a highly palatable sweet solution, demonstrating that the effects of tat-cyclotraxin-B are specific for cocaine reinforcement. Cocaine self-administration increased TrkB signaling and activated the downstream Akt pathway in the nucleus accumbens, and had opposite effects in the prefrontal cortex. Pretreatment with tat-cyclotraxin-B normalized protein levels in these two dopamine-innervated brain regions. Cocaine self-administration also increased TrkB signaling in the ventral tegmental area, where the dopaminergic projections originate, but pretreatment with tat-cyclotraxin-B did not alter this effect. Altogether, our data show that systemic administration of a brain-penetrant TrkB antagonist leads to brain region-specific effects and may be a potential pharmacological strategy for the treatment of cocaine addiction. SIGNIFICANCE STATEMENT Brain-derived neurotrophic factor (BDNF) signaling through TrkB receptors plays a well established role in cocaine reinforcement. However, local

  20. [Extinction of brain activation responses to direct electrical stimulation of its structures in normal awake cats].

    PubMed

    Kratin, Iu G; Andreeva, V N; Iragashev, M S

    1975-03-01

    In unrestrained cats, repeated electric stimulation of the mesencephalic reticular formation (MRF), center median (CM) of the thalamus, and different cortical areas: both the low--and the high--threshold points (in regard to the brain activation), with the threshold strength current evoked similar EEG reactions of activation which diminished and disappeared after 3--5 repetitions of the stimuli. The moderate strength current evoked, apart from the EEG activation, pseudoviolent movements (turning of the head, etc.) and changes in the breathing rate. All these reactions could be extinguidhed by sufficient number of repetitions of stimuli, the effector reactions disappearing first, the EEG changes--last. The essential difference of the stimulation effects emerged when the strong current stimulation was used. In this case, when stimulating the high-threshold cortical points, the EEG and effector reactions could be abolished during long enough repetition of the stimuli, but it was impossible when stimulating the low-threshold cortical points, the MRF or CM: all the reactions stayed intense and stable, the animals became highly irritated. The data obtained are discussed from the point of view of the authors' concept of the interaction between the activating and integrative analysing mechanisms of the brain.

  1. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  2. Adhesion of mononuclear cells from multiple sclerosis patients to cerebral vessels in cryostat sections of normal human brain.

    PubMed

    Zaffaroni, M; Martinazzi, S; Crivelli, F; Ghezzi, A; Zampieri, A; Martinazzi, M; Zibetti, A; Canal, N

    1999-09-01

    Leukocyte extravasation across the blood-brain barrier is a critical event in the pathogenesis of multiple sclerosis (MS). This complex multistep process includes the adhesion of leukocytes to the endothelial cells of the central nervous system microvasculature. To investigate this phenomenon in MS, we developed a modified version of the frozen-section assay. Peripheral blood mononuclear cells (PBM) from 26 MS patients, 26 healthy controls and 10 patients with other inflammatory non- neurological diseases (OIND) were co-incubated with cryostat sections of normal brain white matter, immunohistochemically labelled with anti-CD45 antibody and counterstained with Giemsa stain. CD45-positive PBM adherent to transected microvasculature were counted with an automated image analyzer. MS patients showed an increased number of vessel-bound PBM (48.8 +/- 36.4) with respect to healthy controls (27.4 +/- 20.7, P = 0.01) and OIND patients (22.6 +/- 7.8, P = 0.01). Significant differences were also obtained counting the number of vessel-bound PBM as a percent of total vascular cells between MS patients (12.7 +/- 7.2%) and healthy controls (6.9 +/- 5.4%, P = 0.002) or OIND patients (7.4 +/- 4.4%, P = 0.03). We confirm that PBM from MS patients show an increased potential of binding to cerebral vessels. The frozen-section assay provides a unique tool to study in situ the molecular interactions of leukocytes with brain vascular structures.

  3. Cephalic Index in the First Three Years of Life: Study of Children with Normal Brain Development Based on Computed Tomography

    PubMed Central

    Bajor, Grzegorz; Gruszczyńska, Katrzyna; Baron, Jan; Markowski, Jarosław; Machnikowska-Sokołowska, Magdalena

    2014-01-01

    Cephalic index is a highly useful method for planning surgical procedures, as well as assessing their effectiveness in correcting cranial deformations in children. There are relatively very few studies measuring cephalic index in healthy Caucasian young children. The aim of our study was to develop a classification of current cephalic index for healthy Caucasian children up to 3 years of age with normal brain development, using axial slice computer tomography performed with very thin slices (0.5 mm) resulting in more accurate measurements. 180 healthy infants (83 females and 97 males) were divided into 5 age categories: 0–3, 4–6, 7–12, 13–24, and 25–36 months. The average value of cephalic index in children up to 3 years of age amounted to 81.45 ± 7.06. The index value in case of children under 3 months was 80.19, 4 to 6 months was 81.45, 7 to 12 months was 83.15, in children under 2 years was 81.05, and in children under 3 years was 79.76. Mesocephaly is the dominating skull shape in children. In this study, we formulated a classification of current cephalic indices of children with normal brain development. Our date appears to be of utmost importance in anthropology, anatomy forensic medicine, and genetics. PMID:24688395

  4. Involvement of Notch1 signaling in neurogenesis in the subventricular zone of normal and ischemic rat brain in vivo.

    PubMed

    Wang, Xiaomei; Mao, Xiaoou; Xie, Lin; Greenberg, David A; Jin, Kunlin

    2009-10-01

    The Notch1 signaling pathway is regarded as one of the main regulators of neural stem cell behavior during development, but its role in the adult brain is less well understood. We found that Notch1 was mainly expressed in doublecortin (DCX)-positive cells corresponding to newborn neurons, whereas the Notch1 ligand, Jagged1, was predominantly expressed in glial fibrillary acidic protein (GFAP)-positive astrocytic cells in the subventricular zone (SVZ) of the normal adult brain. These findings were confirmed by conditional depletion of DCX-positive cells in transgenic mice carrying herpes simplex virus thymidine kinase (HSV-TK) under the control of the DCX promoter. In addition, the activated form of Notch1 (Notch intracellular domain, NICD) and its downstream transcriptional targets, Hes1 and sonic hedgehog (Shh), were also expressed in SVZ cells. Increased activation of Notch1 signaling increased SVZ cell proliferation, whereas inhibiting Notch1 signaling resulted in a reduction of proliferating cells in the SVZ. Levels of NICD, Hes1, and Shh were increased in the SVZ at 4 and 24 h after focal cerebral ischemia. Finally, ischemia-induced cell proliferation in the SVZ was blocked by inhibition of the Notch1 signaling pathway, suggesting that Notch1 signaling may have a key role in normal adult and ischemia-induced neurogenesis.

  5. Changing brains: how longitudinal functional magnetic resonance imaging studies can inform us about cognitive and social-affective growth trajectories.

    PubMed

    Crone, Eveline A; Elzinga, Bernet M

    2015-01-01

    Brain imaging studies have demonstrated widespread changes in brain networks which support cognitive and social-affective development. These conclusions, however, are largely based on cross-sectional comparisons, which limits the possibility to investigate growth trajectories and detect individual changes. Understanding individual growth patterns is crucial if we want to ultimately understand how brain development is sensitive to environmental influences such as educational or psychological interventions or childhood maltreatment. Recently, longitudinal brain imaging studies in children and adolescents have taken the first steps into examining cognitive and social-affective brain functions longitudinally with several compelling findings. First, longitudinal measurements show that activations in some brain regions, such as the prefrontal, temporal, and parietal cortex, are relatively stable over time and can be used as predictors for cognitive functions, whereas activations in other brain regions, such as the amygdala and ventral striatum, are much more variable over time. Second, developmental studies reveal how these changes are related to age, puberty, and changes in performance. These findings have implications for understanding how environmental factors influence brain development. An important future direction will be to examine individual characteristics (e.g., genetic, temperamental, personality) which make individuals differentially susceptible to their environment.

  6. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

    PubMed

    Greisen, Mia H; Altar, C Anthony; Bolwig, Tom G; Whitehead, Richard; Wörtwein, Gitta

    2005-03-15

    Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

  7. Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat.

    PubMed

    Jones, Christine Ann; Perez, Emanuele; Amici, Roberto; Luppi, Marco; Baracchi, Francesca; Cerri, Matteo; Dentico, Daniela; Zamboni, Giovanni

    2008-03-05

    The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake-sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP(3) in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature (T(a)). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory T(a); (iv) a significant increase of IP(3) concentration in CC following exposure to low T(a). The earliest and most sensitive effects of lithium appear to be those concerning sleep. These changes are concomitant with biochemical effects that, in spite of a systemic administration of the substance, may be differentiated according to the second messenger involved, the brain region and the ambient condition.

  8. Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects

    PubMed Central

    Mizoguchi, Kazushige; Ikarashi, Yasushi

    2017-01-01

    Yokukansan (YKS), a traditional Japanese Kampo medicine, has indications for use in night crying and irritability in children, as well as neurosis and insomnia. It is currently also used for the remedy of the behavioral and psychological symptoms of dementia (BPSD), such as aggressiveness, agitation, and hallucinations. In parallel with clinical evidence, a significant amount of fundamental researches have been undertaken to clarify the neuropsychopharmacological efficacies of YKS, with approximately 70 articles, including our own, being published to date. Recently, we reviewed the neuropharmacological mechanisms of YKS, including its effects on glutamatergic, serotonergic, and dopaminergic neurotransmission, and pharmacokinetics of the ingredients responsible for the effects. This review is aimed to integrate the information regarding the psychopharmacological effects of YKS with the brain regions known to be affected, to facilitate our understanding of the clinical efficacy of YKS. In this review, we first show that YKS has several effects that act to improve symptoms that are similar to BPSDs, like aggressiveness, hallucinations, anxiety, and sleep disturbance, as well as symptoms like tardive dyskinesia and cognitive deficits. We next provide the evidence showing that YKS can interact with various brain regions, including the cerebral cortex, hippocampus, striatum, and spinal cord, dysfunctions of which are related to psychiatric symptoms, cognitive deficits, abnormal behaviors, and dysesthesia. In addition, the major active ingredients of YKS, geissoschizine methyl ether and 18β-glycyrrhetinic acid, are shown to predominantly bind to the frontal cortex and hippocampus, respectively. Our findings suggest that YKS has multiple psychopharmacological effects, and that these are probably mediated by interactions among several brain regions. In this review, we summarize the available information about the valuable effects of a multicomponent medicine YKS on complex

  9. Diazepam affects the nuclear thyroid hormone receptor density and their expression levels in adult rat brain.

    PubMed

    Constantinou, Caterina; Bolaris, Stamatis; Valcana, Theony; Margarity, Marigoula

    2005-07-01

    Thyroid hormones (THs) are involved in the occurrence of anxiety and affective disorders; however, the effects following an anxiolytic benzodiazepine treatment, such as diazepam administration, on the mechanism of action of thyroid hormones has not yet been investigated. The effect of diazepam on the in vitro nuclear T3 binding, on the relative expression of the TH receptors (TRs) and on the synaptosomal TH availability were examined in adult rat cerebral hemispheres 24 h after a single intraperitoneal dose (5 mg/kg BW) of this tranquillizer. Although, diazepam did not affect the availability of TH either in blood circulation or in the synaptosomal fraction, it decreased (33%) the nuclear T3 maximal binding density (B(max)). No differences were observed in the equilibrium dissociation constant (K(d)). The TRalpha2 variant (non-T3-binding) mRNA levels were increased by 33%, whereas no changes in the relative expression of the T3-binding isoforms of TRs (TRalpha1, TRbeta1) were observed. This study shows that a single intraperitoneal injection of diazepam affects within 24 h, the density of the nuclear TRs and their expression pattern. The latest effect occurs in an isoform-specific manner involving specifically the TRalpha2 mRNA levels in adult rat brain.

  10. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    PubMed

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  11. Sustained sleep fragmentation affects brain temperature, food intake and glucose tolerance in mice.

    PubMed

    Baud, Maxime O; Magistretti, Pierre J; Petit, Jean-Marie

    2013-02-01

    Sleep fragmentation is present in numerous sleep pathologies and constitutes a major feature of patients with obstructive sleep apnea. A prevalence of metabolic syndrome, diabetes and obesity has been shown to be associated to obstructive sleep apnea. While sleep fragmentation has been shown to impact sleep homeostasis, its specific effects on metabolic variables are only beginning to emerge. In this context, it is important to develop realistic animal models that would account for chronic metabolic effects of sleep fragmentation. We developed a 14-day model of instrumental sleep fragmentation in mice, and show an impact on both brain-specific and general metabolism. We first report that sleep fragmentation increases food intake without affecting body weight. This imbalance was accompanied by the inability to adequately decrease brain temperature during fragmented sleep. In addition, we report that sleep-fragmented mice develop glucose intolerance. We also observe that sleep fragmentation slightly increases the circadian peak level of glucocorticoids, a factor that may be involved in the observed metabolic effects. Our results confirm that poor-quality sleep with sustained sleep fragmentation has similar effects on general metabolism as actual sleep loss. Altogether, these results strongly suggest that sleep fragmentation is an aggravating factor for the development of metabolic dysfunctions that may be relevant for sleep disorders such as obstructive sleep apnea.

  12. Prenatal ethanol exposure differentially affects hippocampal neurogenesis in the adolescent and aged brain.

    PubMed

    Gil-Mohapel, J; Titterness, A K; Patten, A R; Taylor, S; Ratzlaff, A; Ratzlaff, T; Helfer, J; Christie, B R

    2014-07-25

    Exposure to ethanol in utero is associated with a myriad of sequelae for the offspring. Some of these effects are morphological in nature and noticeable from birth, while others involve more subtle changes to the brain that only become apparent later in life when the individuals are challenged cognitively. One brain structure that shows both functional and structural deficits following prenatal ethanol exposure is the hippocampus. The hippocampus is composed of two interlocking gyri, the cornu ammonis (CA) and the dentate gyrus (DG), and they are differentially affected by prenatal ethanol exposure. The CA shows a more consistent loss in neuronal numbers, with different ethanol exposure paradigms, than the DG, which in contrast shows more pronounced and consistent deficits in synaptic plasticity. In this study we show that significant deficits in adult hippocampal neurogenesis are apparent in aged animals following prenatal ethanol exposure. Deficits in hippocampal neurogenesis were not apparent in younger animals. Surprisingly, even when ethanol exposure occurred in conjunction with maternal stress, deficits in neurogenesis did not occur at this young age, suggesting that the capacity for neurogenesis is highly conserved early in life. These findings are unique in that they demonstrate for the first time that deficits in neurogenesis associated with prenatal ethanol consumption appear later in life.

  13. Evaluating How Circle of Willis Topology Affects Embolus Distribution in the Brain

    NASA Astrophysics Data System (ADS)

    Jani, Neel; Mukherjee, Debanjan; Shadden, Shawn

    2016-11-01

    Embolic stroke occurs when fragmented cellular or acellular material (emboli) travels to the brain to occlude an artery. Understanding the transport of emboli across unsteady, pulsatile flow in complex arterial geometries is challenging and influenced by a range of factors, including patient anatomy. The work herein develops the modeling and mechanistic understanding of how embolus transport is affected by the arterial connections at the base of the brain known as the Circle of Willis (CoW). A majority of the human population has an incomplete CoW anatomy, with connections either missing or ill-developed. We employ numerical simulations combining image-based modeling, computational fluid dynamics, discrete particle dynamics, and a sampling based analysis to compare collateral flow through the most prevalent CoW topologies, to determine embolus distribution fractions among vessels in the CoW, and to investigate the role of inertial effects in causing differences in flow and embolus distribution. The computational framework developed enables characterization of the complex interplay of anatomy, hemodynamics, and embolus properties in the context of embolic stroke as well as statistical analysis of embolism risks across common CoW variations.

  14. Contralateral targeting of the corpus callosum in normal and pathological brain function.

    PubMed

    Fenlon, Laura R; Richards, Linda J

    2015-05-01

    The corpus callosum connects the two cortical hemispheres of the mammalian brain and is susceptible to structural defects during development, which often result in significant neuropsychological dysfunction. To date, such individuals have been studied primarily with regards to the integrity of the callosal tract at the midline. However, the mechanisms regulating the contralateral targeting of the corpus callosum, after midline crossing has occurred, are less well understood. Recent evidence suggests that defects in contralateral targeting can occur in isolation from midline-tract malformations, and may have significant functional implications. We propose that contralateral targeting is a crucially important and relatively under-investigated event in callosal development, and that defects in this process may constitute an undiagnosed phenotype in several neurological disorders.

  15. Starting Smart: How Early Experiences Affect Brain Development. An Ounce of Prevention Fund Paper.

    ERIC Educational Resources Information Center

    Ounce of Prevention Fund.

    Recent research has provided great insight into the impact of early experience on brain development. It is now believed that brain growth is highly dependent upon early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring…

  16. Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

    SciTech Connect

    Kronfeld, Andrea; Müller-Forell, Wibke; Buchholz, Hans-Georg; Maus, Stephan; Reuss, Stefan; Schreckenberger, Mathias; Miederer, Isabelle; Lutz, Beat

    2015-12-15

    Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawley rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL

  17. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.

    PubMed

    Zhang, Deng-Feng; Li, Jin; Wu, Huan; Cui, Yue; Bi, Rui; Zhou, He-Jiang; Wang, Hui-Zhen; Zhang, Chen; Wang, Dong; Kong, Qing-Peng; Li, Tao; Fang, Yiru; Jiang, Tianzi; Yao, Yong-Gang

    2016-03-01

    The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

  18. Sex differences in the brain response to affective scenes with or without humans.

    PubMed

    Proverbio, Alice Mado; Adorni, Roberta; Zani, Alberto; Trestianu, Laura

    2009-10-01

    Recent findings have demonstrated that women might be more reactive than men to viewing painful stimuli (vicarious response to pain), and therefore more empathic [Han, S., Fan, Y., & Mao, L. (2008). Gender difference in empathy for pain: An electrophysiological investigation. Brain Research, 1196, 85-93]. We investigated whether the two sexes differed in their cerebral responses to affective pictures portraying humans in different positive or negative contexts compared to natural or urban scenarios. 440 IAPS slides were presented to 24 Italian students (12 women and 12 men). Half the pictures displayed humans while the remaining scenes lacked visible persons. ERPs were recorded from 128 electrodes and swLORETA (standardized weighted Low-Resolution Electromagnetic Tomography) source reconstruction was performed. Occipital P115 was greater in response to persons than to scenes and was affected by the emotional valence of the human pictures. This suggests that processing of biologically relevant stimuli is prioritized. Orbitofrontal N2 was greater in response to positive than negative human pictures in women but not in men, and not to scenes. A late positivity (LP) to suffering humans far exceeded the response to negative scenes in women but not in men. In both sexes, the contrast suffering-minus-happy humans revealed a difference in the activation of the occipito/temporal, right occipital (BA19), bilateral parahippocampal, left dorsal prefrontal cortex (DPFC) and left amygdala. However, increased right amygdala and right frontal area activities were observed only in women. The humans-minus-scenes contrast revealed a difference in the activation of the middle occipital gyrus (MOG) in men, and of the left inferior parietal (BA40), left superior temporal gyrus (STG, BA38) and right cingulate (BA31) in women (270-290 ms). These data indicate a sex-related difference in the brain response to humans, possibly supporting human empathy.

  19. Altered Expression Patterns of Inflammation-Associated and Trophic Molecules in Substantia Nigra and Striatum Brain Samples from Parkinson's Disease, Incidental Lewy Body Disease and Normal Control Cases

    PubMed Central

    Walker, Douglas G.; Lue, Lih-Fen; Serrano, Geidy; Adler, Charles H.; Caviness, John N.; Sue, Lucia I.; Beach, Thomas G.

    2016-01-01

    Evidence of inflammation has been consistently associated with pathology in Parkinson's disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD, and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL)-5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity

  20. Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis.

    PubMed

    Frontera, Jimena Laura; Cervino, Ailen Soledad; Jungblut, Lucas David; Paz, Dante Agustín

    2015-03-01

    Olfactory epithelium has the capability to continuously regenerate olfactory receptor neurons throughout life. Adult neurogenesis results from proliferation and differentiation of neural stem cells, and consequently, olfactory neuroepithelium offers an excellent opportunity to study neural regeneration and the factors involved in the maintenance and regeneration of all their cell types. We analyzed the expression of BDNF in the olfactory system under normal physiological conditions as well as during a massive regeneration induced by chemical destruction of the olfactory epithelium in Xenopus laevis larvae. We described the expression and presence of BDNF in the olfactory epithelium and bulb. In normal physiological conditions, sustentacular (glial) cells and a few scattered basal (stem) cells express BDNF in the olfactory epithelium as well as the granular cells in the olfactory bulb. Moreover, during massive regeneration, we demonstrated a drastic increase in basal cells expressing BDNF as well as an increase in BDNF in the olfactory bulb and nerve. Together these results suggest an important role of BDNF in the maintenance and regeneration of the olfactory system.

  1. Ischaemic and haemorrhagic brain lesions in newborns with seizures and normal Apgar scores.

    PubMed Central

    Mercuri, E.; Cowan, F.; Rutherford, M.; Acolet, D.; Pennock, J.; Dubowitz, L.

    1995-01-01

    Serial ultrasound scans and conventional and diffusion weighted magnetic resonance imaging (MRI) were performed on 16 neonates who presented with seizures. The Apgar scores were normal and subsequently no metabolic or infective cause could be found. The aim of the study was to evaluate the extent to which early sequential imaging can elucidate the cause of seizures in apparently neurologically normal infants. Fourteen of the infants had haemorrhagic or ischaemic lesions on MRI and these were detected by ultrasound scanning in 11. Early ultrasound scanning detected the haemorrhagic lesions but the ischaemic lesions were often not seen until the end of the first week of life. Early MRI, however, was able to detect all the ischaemic lesions. The evolution of the insult could be timed by using serial ultrasound scans and a combination of diffusion weighted and conventional MRI during the first week of life, confirming a perinatal insult even in the absence of fetal distress. Although the aetiology of these lesions remains obscure, serial ultrasound scans will detect the presence of cerebral lesions in neonates presenting with isolated seizures but additional MRI sequences will give better definition on type, site, and extent of the pathology. Images Figures 5 and 6 Figure 2 Figures 3 and 4 Figure 1 PMID:7583609

  2. A Triple Network Connectivity Study of Large-Scale Brain Systems in Cognitively Normal APOE4 Carriers

    PubMed Central

    Wu, Xia; Li, Qing; Yu, Xinyu; Chen, Kewei; Fleisher, Adam S.; Guo, Xiaojuan; Zhang, Jiacai; Reiman, Eric M.; Yao, Li; Li, Rui

    2016-01-01

    The triple network model, consisting of the central executive network (CEN), salience network (SN) and default mode network (DMN), has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal apolipoprotein e4 (APOE4) carriers who are at risk of Alzheimer’s disease (AD). To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis (ICA) and Bayesian network (BN) approach. Our findings indicated altered within-network connectivity that suggests future cognitive decline risk, and preserved between-network connectivity that may support their current preserved cognition in the cognitively normal APOE4 allele carriers. The study provides novel sights into our understanding of the risk factors for AD and their influence on the triple network model of major psychopathology. PMID:27733827

  3. Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma.

    PubMed

    Prasanna, Venkatesh K; Venkataramana, Neelam K; Dwarakanath, B S; Santhosh, Vani

    2009-09-01

    2-Deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, enhances radiation damage selectively in tumor cells by modulating damage response pathways resulting in cell death in vitro and local tumor control. Phase I and II clinical trials in patients with malignant glioma have shown excellent tolerance to a combined treatment of orally administered 2-DG and hypofractionated radiotherapy without any acute toxicity and late radiation damage. Phase III efficacy trials are currently at an advanced stage. Re-exploratory surgery performed in 13 patients due to persistent symptoms of elevated ICP and mass effect at different follow-up periods revealed extensive tumor necrosis with well-preserved normal brain tissue adjoining the tumor included in the treatment volume as revealed by a histological examination. These observations are perhaps the first clinical evidences for differential effects of 2-DG on tumors and normal tissues in conformity with earlier in vitro and in vivo studies in normal and tumor-bearing mice.

  4. Increased CD147 and MMP-9 expression in the normal rat brain after gamma irradiation.

    PubMed

    Li, Hong; Wei, Ming; Li, Shenghui; Zhou, Ziwei; Xu, Desheng

    2013-01-01

    Radiation-induced vascular injury is a major complication of Gamma knife surgery (GKS). Previous studies have shown that CD147 and MMP-9 are closely associated with vascular remodeling and pathological angiogenesis. Thus, we analysed changes in CD147 and MMP-9 expression in the cerebral cortex to investigate the correlation between CD147 and MMP-9 in the rat following GKS. Adult male Wistar rats were subjected to GKS at a maximum dose of 75 Gy and then euthanized 1 to 12 weeks later. Using immunohistochemistry and western blot analysis, we found that CD147 and MMP-9 expression were markedly upregulated in the target area 8-12 weeks after GKS when compared with the control group. Immunofluorescent double staining demonstrated that CD147 signals colocalized with CD31, GFAP and MMP-9-positive cells. Importantly, CD147 levels correlated with increased MMP-9 expression in irradiated brain tissue. For the first time, these data demonstrate a potential relationship between CD147 and MMP-9 following GKS. In addition, our study also suggests that CD147 and MMP-9 may play a role in vascular injury after GKS.

  5. The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology.

    PubMed

    Schumann, G; Loth, E; Banaschewski, T; Barbot, A; Barker, G; Büchel, C; Conrod, P J; Dalley, J W; Flor, H; Gallinat, J; Garavan, H; Heinz, A; Itterman, B; Lathrop, M; Mallik, C; Mann, K; Martinot, J-L; Paus, T; Poline, J-B; Robbins, T W; Rietschel, M; Reed, L; Smolka, M; Spanagel, R; Speiser, C; Stephens, D N; Ströhle, A; Struve, M

    2010-12-01

    A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional reactivity, and determining their predictive value for the development of frequent psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents are combined with functional genetics in animal and human models. Results will be validated in 1000 adolescents from the Canadian Saguenay Youth Study. The sample will be followed up longitudinally at the age of 16 years to investigate the predictive value of genetics and intermediate phenotypes for the development of frequent psychiatric disorders. This review describes the strategies the IMAGEN consortium used to meet the challenges posed by large-scale multicentre imaging-genomics investigations. We provide detailed methods and Standard Operating Procedures that we hope will be helpful for the design of future studies. These include standardization of the clinical, psychometric and neuroimaging-acquisition protocols, development of a central database for efficient analyses of large multimodal data sets and new analytic approaches to large-scale genetic neuroimaging analyses.

  6. Neurotoxic effects of exogenous recombinant tissue-type plasminogen activator on the normal rat brain.

    PubMed

    Goto, Hisaharu; Fujisawa, Hirosuke; Oka, Fumiaki; Nomura, Sadahiro; Kajiwara, Koji; Kato, Shoichi; Fujii, Masami; Maekawa, Tsuyoshi; Suzuki, Michiyasu

    2007-04-01

    Thrombolytic therapy with intravenous and intra-arterial recombinant tissue-type plasminogen activator (rtPA) has been established for the treatment of acute ischemic stroke. However, tPA has also been suggested to have neurotoxic effects. The purpose of this study was to examine direct neurotoxicity of rtPA in vivo. The animals (Wistar rats) were divided to the following three groups: low-dose (15 micromol/L) rtPA group (n = 6); high-dose (30 micromol/L) rtPA group (n = 6); and control (physiological saline) group (n = 6). The rtPA solution was perfused into the cortex via a microdialysis probe. The volume of the lesion was quantified histologically by image analysis of the lesions. Blood-brain barrier (BBB) disruption was evaluated by intravenous injection of Evans blue, and injury to the basal lamina was evaluated by immunohistochemistry using an anti-laminin antibody. In the rtPA-perfused animals, a pale lesion was produced around the probe, and microscopically, neurons showed necrotic changes. The volume of the lesions increased significantly as the concentration of perfused rtPA was increased. Marked extravasation of Evans blue was observed, and laminin immunoreactivity of blood vessels in the rtPA-induced lesions was lost. These results suggest that rtPA promotes acute direct neurotoxicity and participates in disruption of the microvascular basal lamina to cause BBB disruption, thereby increasing edema formation.

  7. Brain parenchymal density measurements by CT in demented subjects and normal controls

    SciTech Connect

    Gado, M.; Danziger, W.L.; Chi, D.; Hughes, C.P.; Coben, L.A.

    1983-06-01

    Parachymal density measurements of 14 regions of gray and white matter from each cerebral hemisphere were made from CT scans of 25 subjects who had varying degrees of dementia as measured by a global Clinical Dementia Rating, and also from CT scans of 33 normal control subjects. There were few significant differences between the two groups in the mean density value for each of the regions examined, although several individual psychometric tests did correlate with density changes. Moreover, for six regions in the cerebral cortex, and for one region in the thalamus of each hemisphere, we found no significant correlation between the gray-white matter density difference and dementia. There was, however, a loss of the discriminability between the gray and white matter with an increase in the size of the ventricles. These findings may be attributed to the loss of white matter volume.

  8. Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography

    SciTech Connect

    Tyler, J.L.; Strother, S.C.; Zatorre, R.J.; Alivisatos, B.; Worsley, K.J.; Diksic, M.; Yamamoto, Y.L.

    1988-05-01

    Cerebral glucose utilization (LCMRGI) was measured using the (/sup 18/F)fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values normalized by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical abnormal values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.

  9. Cognitive Deficits, Changes in Synaptic Function, and Brain Pathology in a Mouse Model of Normal Aging

    PubMed Central

    Wu, Tiffany; Hanson, Jesse E.; Alam, Nazia M.; Ngu, Hai; Lauffer, Benjamin E.; Lin, Han H.; Dominguez, Sara L.; Reeder, Jens; Tom, Jennifer; Steiner, Pascal; Foreman, Oded; Prusky, Glen T.

    2015-01-01

    Abstract Age is the main risk factor for sporadic Alzheimer’s disease. Yet, cognitive decline in aged rodents has been less well studied, possibly due to concomitant changes in sensory or locomotor function that can complicate cognitive tests. We tested mice that were 3, 11, and 23 months old in cognitive, sensory, and motor measures, and postmortem measures of gliosis and neural activity (c-Fos). Hippocampal synaptic function was also examined. While age-related impairments were detectable in tests of spatial memory, greater age-dependent effects were observed in tests of associative learning [active avoidance (AA)]. Gross visual function was largely normal, but startle responses to acoustic stimuli decreased with increased age, possibly due to hearing impairments. Therefore, a novel AA variant in which light alone served as the conditioning stimuli was used. Age-related deficits were again observed. Mild changes in vision, as measured by optokinetic responses, were detected in 19- versus 4-month-old mice, but these were not correlated to AA performance. Thus, deficits in hearing or vision are unlikely to account for the observed deficits in cognitive measures. Increased gliosis was observed in the hippocampal formation at older ages. Age-related changes in neural function and plasticity were observed with decreased c-Fos in the dentate gyrus, and decreased synaptic strength and paired-pulse facilitation in CA1 slices. This work, which carefully outlines age-dependent impairments in cognitive and synaptic function, c-Fos activity, and gliosis during normal aging in the mouse, suggests robust translational measures that will facilitate further study of the biology of aging. PMID:26473169

  10. Dopamine Transporter Gene Variant Affecting Expression in Human Brain is Associated with Bipolar Disorder

    PubMed Central

    Pinsonneault, Julia K; Han, Dawn D; Burdick, Katherine E; Kataki, Maria; Bertolino, Alessandro; Malhotra, Anil K; Gu, Howard H; Sadee, Wolfgang

    2011-01-01

    The gene encoding the dopamine transporter (DAT) has been implicated in CNS disorders, but the responsible polymorphisms remain uncertain. To search for regulatory polymorphisms, we measured allelic DAT mRNA expression in substantia nigra of human autopsy brain tissues, using two marker SNPs (rs6347 in exon 9 and rs27072 in the 3′-UTR). Allelic mRNA expression imbalance (AEI), an indicator of cis-acting regulatory polymorphisms, was observed in all tissues heterozygous for either of the two marker SNPs. SNP scanning of the DAT locus with AEI ratios as the phenotype, followed by in vitro molecular genetics studies, demonstrated that rs27072 C>T affects mRNA expression and translation. Expression of the minor T allele was dynamically regulated in transfected cell cultures, possibly involving microRNA interactions. Both rs6347 and rs3836790 (intron8 5/6 VNTR) also seemed to affect DAT expression, but not the commonly tested 9/10 VNTR in the 3′UTR (rs28363170). All four polymorphisms (rs6347, intron8 5/6 VNTR, rs27072 and 3′UTR 9/10 VNTR) were genotyped in clinical cohorts, representing schizophrenia, bipolar disorder, depression, and controls. Only rs27072 was significantly associated with bipolar disorder (OR=2.1, p=0.03). This result was replicated in a second bipolar/control population (OR=1.65, p=0.01), supporting a critical role for DAT regulation in bipolar disorder. PMID:21525861

  11. Affective three-dimensional brain-computer interface created using a prism array-based display

    NASA Astrophysics Data System (ADS)

    Mun, Sungchul; Park, Min-Chul

    2014-12-01

    To avoid the vergence-accommodation mismatch and provide a strong sense of presence to users, we applied a prism array-based display when presenting three-dimensional (3-D) objects. Emotional pictures were used as visual stimuli to increase the signal-to-noise ratios of steady-state visually evoked potentials (SSVEPs) because involuntarily motivated selective attention by affective mechanisms can enhance SSVEP amplitudes, thus producing increased interaction efficiency. Ten male and nine female participants voluntarily participated in our experiments. Participants were asked to control objects under three viewing conditions: two-dimension (2-D), stereoscopic 3-D, and prism. The participants performed each condition in a counter-balanced order. One-way repeated measures analysis of variance showed significant increases in the positive predictive values in the prism condition compared to the 2-D and 3-D conditions. Participants' subjective ratings of realness and engagement were also significantly greater in the prism condition than in the 2-D and 3-D conditions, while the ratings for visual fatigue were significantly reduced in the prism condition than in the 3-D condition. The proposed methods are expected to enhance the sense of reality in 3-D space without causing critical visual fatigue. In addition, people who are especially susceptible to stereoscopic 3-D may be able to use the affective brain-computer interface.

  12. Sleep deprivation does not affect neuronal susceptibility to mild traumatic brain injury in the rat

    PubMed Central

    Caron, Aimee M; Stephenson, Richard

    2015-01-01

    Mild and moderate traumatic brain injuries (TBIs) (and concussion) occur frequently as a result of falls, automobile accidents, and sporting activities, and are a major cause of acute and chronic disability. Fatigue and excessive sleepiness are associated with increased risk of accidents, but it is unknown whether prior sleep debt also affects the pathophysiological outcome of concussive injury. Using the “dark neuron” (DN) as a marker of reversible neuronal damage, we tested the hypothesis that acute (48 hours) total sleep deprivation (TSD) and chronic sleep restriction (CSR; 10 days, 6-hour sleep/day) affect DN formation following mild TBI in the rat. TSD and CSR were administered using a walking wheel apparatus. Mild TBI was administered under anesthesia using a weight-drop impact model, and the acute neuronal response was observed without recovery. DNs were detected using standard bright-field microscopy with toluidine blue stain following appropriate tissue fixation. DN density was low under home cage and sleep deprivation control conditions (respective median DN densities, 0.14% and 0.22% of neurons), and this was unaffected by TSD alone (0.1%). Mild TBI caused significantly higher DN densities (0.76%), and this was unchanged by preexisting acute or chronic sleep debt (TSD, 0.23%; CSR, 0.7%). Thus, although sleep debt may be predicted to increase the incidence of concussive injury, the present data suggest that sleep debt does not exacerbate the resulting neuronal damage. PMID:26124685

  13. The Brain Basis of Positive and Negative Affect: Evidence from a Meta-Analysis of the Human Neuroimaging Literature.

    PubMed

    Lindquist, Kristen A; Satpute, Ajay B; Wager, Tor D; Weber, Jochen; Barrett, Lisa Feldman

    2016-05-01

    The ability to experience pleasant or unpleasant feelings or to represent objects as "positive" or "negative" is known as representing hedonic "valence." Although scientists overwhelmingly agree that valence is a basic psychological phenomenon, debate continues about how to best conceptualize it scientifically. We used a meta-analysis of 397 functional magnetic resonance imaging (fMRI) and positron emission tomography studies (containing 914 experimental contrasts and 6827 participants) to test 3 competing hypotheses about the brain basis of valence: the bipolarity hypothesis that positive and negative affect are supported by a brain system that monotonically increases and/or decreases along the valence dimension, the bivalent hypothesis that positive and negative affect are supported by independent brain systems, and the affective workspace hypothesis that positive and negative affect are supported by a flexible set of valence-general regions. We found little evidence for the bipolar or bivalent hypotheses. Findings instead supported the hypothesis that, at the level of brain activity measurable by fMRI, valence is flexibly implemented across instances by a set of valence-general limbic and paralimbic brain regions.

  14. Plasticity in the development of handedness: evidence from normal development and early asymmetric brain injury.

    PubMed

    Corbetta, Daniela; Williams, Joshua; Snapp-Childs, Winona

    2006-09-01

    Previous research revealed that shifting patterns of hand preference in the first year of life are linked to infants' sensory-motor experiences as they learn to sit, creep, and walk. In this report, we examine whether new and different forms of locomotion and sensory-motor experiences similarly contribute to alter patterns of hand preference in early development. We examined the cases of three infants with unique developmental histories. Two infants adopted distinctive forms of locomotion in lieu of typical hands-and-knees crawling. One infant scooted using both hands and legs in a coupled fashion, while the other infant performed an asymmetrical, left-biased belly-crawl using only one arm to drag his body. The third infant suffered damage to his left-brain hemisphere shortly after birth and received intense physical therapy to his right arm as a result of it. We followed all three infants on a weekly basis and tracked changes in their reaching behavior, mode of locomotion, and postural achievements. The two infants with unique locomotor patterns displayed changes in hand preference that reciprocated the arm patterns that they used during locomotion. The infant who coupled his body for scooting began to reach bimanually, while the infant who adopted the left-biased belly-crawl developed a strong unimanual, right-hand, preference. The infant with left-hemisphere damage initially displayed a right-hand preference, then a temporary decline in preferred hand use as he began to cruise and walk, and ultimately resumed a right-hand preference in the 2nd year of life. This data is consistent with previous work showing that the development of hand preference in the 1st year of life is highly malleable and sensitive to a variety of new sensory-motor experiences.

  15. Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

    PubMed Central

    Jung, Yeon Suk; Park, Jung Hwa; Kim, Hyunha; Kim, So Young; Hwang, Ji Young; Hong, Ki Whan; Bae, Sun Sik; Choi, Byung Tae; Lee, Sae-Won; Shin, Hwa Kyoung

    2016-01-01

    Aim: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. Methods: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg-1·d-1, po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators. Results: In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, pre-administration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total- and LDL-cholesterol levels. Conclusion: Probucol inhibits LPS-induced microglia activation and

  16. Brain Tumor Therapy-Induced Changes in Normal-Appearing Brainstem Measured With Longitudinal Diffusion Tensor Imaging

    SciTech Connect

    Hua Chiaho; Merchant, Thomas E.; Gajjar, Amar; Broniscer, Alberto; Zhang, Yong; Li Yimei; Glenn, George R.; Kun, Larry E.; Ogg, Robert J.

    2012-04-01

    Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in

  17. Emotional Granularity Effects on Event-Related Brain Potentials during Affective Picture Processing

    PubMed Central

    Lee, Ja Y.; Lindquist, Kristen A.; Nam, Chang S.

    2017-01-01

    There is debate about whether emotional granularity, the tendency to label emotions in a nuanced and specific manner, is merely a product of labeling abilities, or a systematic difference in the experience of emotion during emotionally evocative events. According to the Conceptual Act Theory of Emotion (CAT) (Barrett, 2006), emotional granularity is due to the latter and is a product of on-going temporal differences in how individuals categorize and thus make meaning of their affective states. To address this question, the present study investigated the effects of individual differences in emotional granularity on electroencephalography-based brain activity during the experience of emotion in response to affective images. Event-related potentials (ERP) and event-related desynchronization and synchronization (ERD/ERS) analysis techniques were used. We found that ERP responses during the very early (60–90 ms), middle (270–300 ms), and later (540–570 ms) moments of stimulus presentation were associated with individuals’ level of granularity. We also observed that highly granular individuals, compared to lowly granular individuals, exhibited relatively stable desynchronization of alpha power (8–12 Hz) and synchronization of gamma power (30–50 Hz) during the 3 s of stimulus presentation. Overall, our results suggest that emotional granularity is related to differences in neural processing throughout emotional experiences and that high granularity could be associated with access to executive control resources and a more habitual processing of affective stimuli, or a kind of “emotional complexity.” Implications for models of emotion are also discussed. PMID:28392761

  18. The diversity of GABA(A) receptor subunit distribution in the normal and Huntington's disease human brain.

    PubMed

    Waldvogel, H J; Faull, R L M

    2015-01-01

    GABA(A) receptors are assembled into pentameric receptor complexes from a total of 19 different subunits derived from a variety of different subunit classes (α1-6, β1-3, γ1-3, δ, ɛ, θ, and π) which surround a central chloride ion channel. GABA(A) receptor complexes are distributed heterogeneously throughout the brain and spinal cord and are activated by the extensive GABAergic inhibitory system. In this chapter, we describe the heterogeneous distribution of six of the most widely distributed subunits (α1, α2, α3, β2,3, and γ2) throughout the human basal ganglia. This review describes the studies we have carried out on the normal and Huntington's disease human basal ganglia using autoradiographic labeling and immunohistochemistry in the human basal ganglia. GABA(A) receptors are known to react to changing conditions in the brain in neurological disorders, especially in Huntington's disease and display a high degree of plasticity which is thought to compensate for loss of function caused by disease. In Huntington's disease, the variable loss of GABAergic medium spiny striatopallidal projection neurons is associated with a loss of GABA(A) receptor subunits in the striosome and/or the matrix compartments of the striatum. By contrast in the globus pallidus, a loss of the GABAergic striatal projection neurons results in a dramatic upregulation of subunits on the large postsynaptic pallidal neurons; this is thought to be a compensatory plastic mechanism resulting from the loss of striatal GABAergic input. Most interestingly, our studies have revealed that the subventricular zone overlying the caudate nucleus contains a variety of proliferating progenitor stem cells that possess a heterogeneity of GABA(A) receptor subunits which may play a role in human brain repair mechanisms.

  19. Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain.

    PubMed

    D'Arceuil, Helen; Coimbra, Alexandre; Triano, Pamela; Dougherty, Margaret; Mello, Julie; Moseley, Michael; Glover, Gary; Lansberg, Maarten; Blankenberg, Francis

    2013-12-01

    The brain demonstrates spontaneous low-frequency (<0.1 Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.5 at 3 T in primates and humans. We evaluated the use of ferumoxytol for steady state, resting state FMRI (CBV-rs-fMRI) and relative cerebral blood volume (rCBV) mapping, at 3T, in healthy volunteers. All standard resting state networks (RSNs) were identified in all subjects. On average the RSN Z statistics (MELODIC independent components) and volumes of the visual and default mode (DMN) networks were comparable. rCBV values were averaged for the visual (Vis) and DMN networks and correlated with the corresponding DMN and visual network Z statistics. There was a negative correlation between the rCBV and the Z statistics for the DMN, for both BOLD and CBV-rs-fMRI contrast (R2=0.63, 0.76). A similar correlation was not found for the visual network. Short repetition time rs-fMRI data were Fourier transformed to evaluate the effect of ferumoxytol on cardiac and respiratory fluctuations in the brain rs-BOLD, CBV signals. Cardiac and respiratory fluctuations decreased to baseline within large vessels post ferumoxytol. Robust rs-fMRI and CBV mapping is possible in normal human brain.

  20. Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults.

    PubMed

    Carvalho, Diego Z; St Louis, Erik K; Boeve, Bradley F; Mielke, Michelle M; Przybelski, Scott A; Knopman, David S; Machulda, Mary M; Roberts, Rosebud O; Geda, Yonas E; Petersen, Ronald C; Jack, Clifford R; Vemuri, Prashanthi

    2017-04-01

    Excessive daytime sleepiness (EDS) and fatigue increases with age. The aim of this study was to investigate the association between EDS and fatigue with cortical thickness and hippocampal volume in cognitively normal, late middle-aged and older adults. We performed a cross-sectional observational study of 1374 cognitively-normal subjects aged 50 years and older who had a structural MRI. Regional cortical thickness and hippocampal volume were measured. Multiple linear regression models were fit to explore associations between EDS and fatigue and structural MRI measures in different brain regions, adjusting for multiple covariates. EDS was defined as Epworth Sleepiness Scale ≥10. Fatigue severity was assessed with the Beck Depression Inventory-2. 208 participants had EDS, 27 had significant fatigue, and 11 had both. Participants with EDS or fatigue had significantly lower cognitive scores, more disturbed sleep, and medical comorbidities. The presence of EDS was associated with both global and regional atrophy, whereas fatigue was more associated with frontal and temporal changes. Cortical thinning predicted by EDS and fatigue was maximal in the temporal region with average reduction of 34.2 μm (95% CI, -54.1, -14.3; P = 0.001) and 90.2 μm (95% CI, -142.1, -38.2; P = 0.001), respectively. Fatigue was also associated with hippocampal volume reduction of -374.2 mm(3) (95% CI, -670.8, -77.7; P = 0.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and 9 additional years of aging, respectively. EDS and fatigue were associated with cortical thickness reduction primarily in regions with increased age-susceptibility, which may indicate accelerated brain aging.

  1. Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging.

    PubMed

    Ding, Xiao-Qi; Sun, Yimeng; Kruse, Bernd; Illies, Till; Zeumer, Hermann; Fiehler, Jens; Lanfermann, Heinrich

    2009-06-01

    Callosal fibres play an important role in psychomotor and cognitive functions. The purpose of this study was to investigate possible microstructural abnormalities of the corpus callosum in children with developmental delay, who have normal conventional brain MR imaging results. Seventeen pediatric patients (aged 1-9 years) with developmental delay were studied. Quantitative T2 and fractional anisotropy (FA) values were measured at the genu and splenium of the corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre density calculations of the CC were also carried out. The results were compared with those of the age-matched healthy subjects. A general elevation of T2 relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886 in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the CC were found only in patients older than 5 years. The study indicates that despite their inconspicuous findings in conventional MRI microstructural brain abnormalities are evident in these pediatric patients suffering from developmental delay.

  2. Breakdown of the normal optic nerve head blood-brain barrier following acute elevation of intraocular pressure in experimental animals.

    PubMed

    Radius, R L; Anderson, D R

    1980-03-01

    Five hours of elevated intraocular pressure produced evidence of an altered blood-brain barrier at the optic nerve head in 27 of 29 monkey eyes. The change in vascular permeability was documented by fluorescein angiography (18 of 21 eyes), by Evans blue fluorescence microscopy (21 of 23 eyes), or by both methods. Leakage occurred from major blood vessels as well as from microvasculature of the nerve head. In 22 eyes, rapid axonal transport was studied after intravitreal injection of tritiated leucine. In 18 of these 22 eyes, autoradiography demonstrated a local interruption of axonal transport. In 15 eyes examined by all three methods, leakage from microvasculature (as opposed to leakage from the major vessels) was loosely associated with severe and widespread blockade of axonal transport at the lamina cribrosa. Although cause-and-effect relationships are not proved, ischemia may be responsible both for the focal endothelial damage with breakdown of the normal blood-brain barrier and for the local abnormalities of axonal transport.

  3. [Functional organization of the sleep state in infants under normal conditions and in brain damage].

    PubMed

    Fantalova, V L

    1975-09-01

    Polygraphic study of day sleep was carried out in 30 nurslings with consideration to the EEG, oculogram, muscle tone indices, variations in skin resistance, respiration, ECG, rheoencephalogram and rheogram of the calf. Nurslings with cerebral affections of perinatal genesis were examined by the same method. It was possible to distinguish the main stages of slow sleep and stages of rapid sleep in young nurslings, although the electroencephalographic expression of the stages in children had its specific features. Age dynamics of the polygraphic picture of sleep showed electroencephalographic, vegetative and motor components of sleep to distinctly coordinate by stages and, at the same time, to possess marked autonomicity; this was also confirmed by analysis of cerebral pathology.

  4. Valence of physical stimuli, not housing conditions, affects behaviour and frontal cortical brain activity in sheep.

    PubMed

    Vögeli, Sabine; Lutz, Janika; Wolf, Martin; Wechsler, Beat; Gygax, Lorenz

    2014-07-01

    Modulation of short-term emotions by long-term mood is little understood but relevant to understand the affective system and of importance in respect to animal welfare: a negative mood might taint experiences, whilst a positive mood might alleviate single negative events. To induce different mood states in sheep housing conditions were varied. Fourteen ewes were group-housed in an unpredictable, stimulus-poor and 15 ewes in a predictable, stimulus-rich environment. Sheep were tested individually for mood in a behavioural cognitive bias paradigm. Also, their reactions to three physical stimuli thought to differ in their perceived valence were observed (negative: pricking, intermediate: slight pressure, positive: kneading). General behaviour, activity, ear movements and positions, and haemodynamic changes in the cortical brain were recorded during stimulations. Generalised mixed-effects models and model probabilities based on the BIC (Bayesian information criterion) were used. Only weak evidence for mood difference was found. Sheep from the unpredictable, stimulus-poor housing condition had a somewhat more negative cognitive bias, showed slightly more aversive behaviour, were slightly more active and moved their ears somewhat more. Sheep most clearly differentiated the negative from the intermediate and positive stimulus in that they exhibited more aversive behaviour, less nibbling, were more active, showed more ear movements, more forward ear postures, fewer backward ear postures, and a stronger decrease in deoxyhaemoglobin when subjected to the negative stimulus. In conclusion, sheep reacted towards stimuli according to their presumed valence but their mood was not strongly influenced by housing conditions. Therefore, behavioural reactions and cortical brain activity towards the stimuli were hardly modulated by housing conditions.

  5. Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause

    PubMed Central

    Ruth, Katherine S.; Bennett, Claire E.; Schoemaker, Minouk J.; Weedon, Michael N.; Swerdlow, Anthony J.; Murray, Anna

    2016-01-01

    STUDY QUESTION Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause? SUMMARY ANSWER The length of repeat alleles within the normal range does not substantially affect risk of early menopause. WHAT IS KNOWN ALREADY There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait. STUDY DESIGN, SIZE, DURATION We analysed cross-sectional baseline survey data collected at recruitment from 2004 to 2010 from a population-based, prospective epidemiological cohort study of >110 000 women to investigate whether repeat allele length was associated with early menopause. PARTICIPANTS/MATERIALS, SETTING, METHOD We included 4333 women from the Breakthrough Generations Study (BGS), of whom 2118 were early menopause cases (menopause under 46 years) and 2215 were controls. We analysed the relationship between length of FMR1 alleles and early menopause using logistic regression with allele length as continuous and categorical variables. We also conducted analyses with the outcome age at menopause as a quantitative trait as well as appropriate sensitivity and exploratory analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no association of the shorter or longer FMR1 allele or their combined genotype with the clinically relevant end point of early menopause in our main analysis. Likewise, there were no associations with age at menopause as a quantitative trait in our secondary analysis. LIMITATIONS, REASONS FOR CAUTION Women with homozygous alleles in the normal range may have undetected FMR1 premutation alleles, although there was no evidence to suggest this. We

  6. Electrogenic properties of the Na+/K+ ATPase control transitions between normal and pathological brain states

    PubMed Central

    Krishnan, Giri P.; Filatov, Gregory; Shilnikov, Andrey

    2015-01-01

    Ionic concentrations fluctuate significantly during epileptic seizures. In this study, using a combination of in vitro electrophysiology, computer modeling, and dynamical systems analysis, we demonstrate that changes in the potassium and sodium intra- and extracellular ion concentrations ([K+] and [Na+], respectively) during seizure affect the neuron dynamics by modulating the outward Na+/K+ pump current. First, we show that an increase of the outward Na+/K+ pump current mediates termination of seizures when there is a progressive increase in the intracellular [Na+]. Second, we show that the Na+/K+ pump current is crucial in maintaining the stability of the physiological network state; a reduction of this current leads to the onset of seizures via a positive-feedback loop. We then present a novel dynamical mechanism for bursting in neurons with a reduced Na+/K+ pump. Overall, our study demonstrates the profound role of the current mediated by Na+/K+ ATPase on the stability of neuronal dynamics that was previously unknown. PMID:25589588

  7. The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride.

    PubMed

    Darsalia, Vladimer; Ortsäter, Henrik; Olverling, Anna; Darlöf, Emilia; Wolbert, Petra; Nyström, Thomas; Klein, Thomas; Sjöholm, Åke; Patrone, Cesare

    2013-04-01

    Type 2 diabetes is a strong risk factor for stroke. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor in clinical use against type 2 diabetes. The aim of this study was to determine the potential antistroke efficacy of linagliptin in type 2 diabetic mice. To understand whether efficacy was mediated by glycemia regulation, a comparison with the sulfonylurea glimepiride was done. To determine whether linagliptin-mediated efficacy was dependent on a diabetic background, experiments in nondiabetic mice were performed. Type 2 diabetes was induced by feeding the mice a high-fat diet for 32 weeks. Mice were treated with linagliptin/glimepiride for 7 weeks. Stroke was induced at 4 weeks into the treatment by transient middle cerebral artery occlusion. Blood DPP-4 activity, glucagon-like peptide-1 (GLP-1) levels, glucose, body weight, and food intake were assessed throughout the experiments. Ischemic brain damage was measured by determining stroke volume and by stereologic quantifications of surviving neurons in the striatum/cortex. We show pronounced antistroke efficacy of linagliptin in type 2 diabetic and normal mice, whereas glimepiride proved efficacious against stroke in normal mice only. These results indicate a linagliptin-mediated neuroprotection that is glucose-independent and likely involves GLP-1. The findings may provide an impetus for the development of DPP-4 inhibitors for the prevention and treatment of stroke in diabetic patients.

  8. Dynamic Susceptibility Contrast Magnetic Resonance Imaging Protocol of the Normal Canine Brain

    PubMed Central

    Stadler, Krystina L.; Pease, Anthony P.; Ballegeer, Elizabeth A.

    2017-01-01

    Perfusion magnetic resonance imaging (MRI), specifically dynamic susceptibility MRI (DSC-MRI) is routinely performed as a supplement to conventional MRI in human medicine for patients with intracranial neoplasia and cerebrovascular events. There is minimal data on the use of DSC-MRI in veterinary patients and a DSC-MRI protocol in the veterinary patient has not been described. Sixteen normal dogs, 6 years or older were recruited for this study. The sample population included 11 large dogs (>11 kg) and 5 small dogs (<11 kg). DSC-MRI was performed on a 1.5-T MRI using an adjusted protocol inherent to the MRI. Contrast media was injected using an automatic power injector. Injections were made after five MR measurements were obtained. Following image acquisition, an arterial input function (AIF) graph mapping the transit time of contrast within the cerebral arteries was generated. The manually selected time points along this graph were used to compute perfusion maps. A dose and rate of 0.1 mmol/kg gadolinium-based contrast media at 3 ml/s followed by 10 ml saline flush at 3 ml/s was used in all dogs greater than 11 kg. In all dogs >11 kg, a useable AIF and perfusion map was generated. One dog less than 11 kg received the same contrast dose and rate. In this patient, the protocol did not generate a useable AIF. The remainder of the dogs less than 11 kg followed a protocol of 0.2 mmol/kg gadolinium-based contrast media at 1.5 ml/s with a 10 ml saline flush at 1.5 ml/s. A useable AIF and perfusion map was generated in the remaining dogs <11 kg using the higher contrast dose and slower rate protocol. This study establishes a contrast dose and administration rate for canine DSC-MRI imaging that is different in dogs greater than 11 kg compared to dogs less than 11 kg. These protocols may be used for future applications to evaluate hemodynamic disturbances in canine intracranial pathology. PMID:28377923

  9. Dynamic Susceptibility Contrast Magnetic Resonance Imaging Protocol of the Normal Canine Brain.

    PubMed

    Stadler, Krystina L; Pease, Anthony P; Ballegeer, Elizabeth A

    2017-01-01

    Perfusion magnetic resonance imaging (MRI), specifically dynamic susceptibility MRI (DSC-MRI) is routinely performed as a supplement to conventional MRI in human medicine for patients with intracranial neoplasia and cerebrovascular events. There is minimal data on the use of DSC-MRI in veterinary patients and a DSC-MRI protocol in the veterinary patient has not been described. Sixteen normal dogs, 6 years or older were recruited for this study. The sample population included 11 large dogs (>11 kg) and 5 small dogs (<11 kg). DSC-MRI was performed on a 1.5-T MRI using an adjusted protocol inherent to the MRI. Contrast media was injected using an automatic power injector. Injections were made after five MR measurements were obtained. Following image acquisition, an arterial input function (AIF) graph mapping the transit time of contrast within the cerebral arteries was generated. The manually selected time points along this graph were used to compute perfusion maps. A dose and rate of 0.1 mmol/kg gadolinium-based contrast media at 3 ml/s followed by 10 ml saline flush at 3 ml/s was used in all dogs greater than 11 kg. In all dogs >11 kg, a useable AIF and perfusion map was generated. One dog less than 11 kg received the same contrast dose and rate. In this patient, the protocol did not generate a useable AIF. The remainder of the dogs less than 11 kg followed a protocol of 0.2 mmol/kg gadolinium-based contrast media at 1.5 ml/s with a 10 ml saline flush at 1.5 ml/s. A useable AIF and perfusion map was generated in the remaining dogs <11 kg using the higher contrast dose and slower rate protocol. This study establishes a contrast dose and administration rate for canine DSC-MRI imaging that is different in dogs greater than 11 kg compared to dogs less than 11 kg. These protocols may be used for future applications to evaluate hemodynamic disturbances in canine intracranial pathology.

  10. A Double Blind Trial of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain Injury

    DTIC Science & Technology

    2014-10-01

    TITLE: A Double Blind Trial of Divalproex Sodium for Affective L ability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL...Final 3. DATES COVERED 15 Sep 2013 to 14 Sep 2014 4. TITLE AND SUBTITLE A Double Blind Trial of Divalproex Sodium for Affective 5a. CONTRACT...subjects treated with divalproex sodium , a mood stabilizing medication, as compared to placebo. To test the primary hypothesis, we propose an 8 week

  11. Longitudinal Metabolite Profiling of Cerebrospinal Fluid in Normal Pressure Hydrocephalus Links Brain Metabolism with Exercise-Induced VEGF Production and Clinical Outcome.

    PubMed

    Huang, He; Yang, Jun; Luciano, Mark; Shriver, Leah P

    2016-07-01

    Idiopathic normal pressure hydrocephalus is a neurological disease caused by abnormal cerebrospinal fluid flow and presents with symptoms such as dementia. Current therapy involves the removal of excess cerebrospinal fluid by shunting. Not all patients respond to this therapy and biomarkers are needed that could facilitate the characterization of patients likely to benefit from this treatment. Here, we measure brain metabolism in normal pressure hydrocephalus patients by performing a novel longitudinal metabolomic profiling study of cerebrospinal fluid. We find that the levels of brain metabolites correlate with clinical parameters, the amount of vascular endothelial growth factor in the cerebrospinal fluid, and environmental stimuli such as exercise. Metabolomic analysis of normal pressure hydrocephalus patients provides insight into changes in brain metabolism that accompany cerebrospinal fluid disorders and may facilitate the development of new biomarkers for this condition.

  12. Minimal changes of thyroid axis activity influence brain functions in young females affected by subclinical hypothyroidism.

    PubMed

    Menicucci, D; Sebastiani, L; Comparini, A; Pingitore, A; Ghelarducci, B; L'Abbate, A; Iervasi, G; Gemignani, A

    2013-03-01

    There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.

  13. Sex differences in perceived pain are affected by an anxious brain.

    PubMed

    Goffaux, Philippe; Michaud, Karine; Gaudreau, Janou; Chalaye, Philippe; Rainville, Pierre; Marchand, Serge

    2011-09-01

    Decades of research confirm that women have greater pain sensitivity than men. Women also show greater overall anxiety sensitivity than men. Given these differences, we hypothesized that sex differences in anxiety would explain sex differences in experienced pain and physiological responses to pain (at both spinal and cortical levels). By measuring subjective pain, state/trait anxiety, nociceptive flexion reflexes, and somatosensory evoked potentials (SEPs), it was possible to test the effects of anxiety on the processing of painful drives at different levels of the neuraxis while also documenting the role played by anxiety on sex differences in experienced pain. Results confirm that women are indeed more sensitive to pain than men. Importantly, this difference was accompanied by a significant sex difference in cortical activity (SEP amplitude) but not spinal nociceptive activity, suggesting that much of the sex difference in experienced pain is attributable to variations in thalamocortical processing and to ensuing changes in the appraisal of and/or emotional response to noxious insult. In support of this claim, we found that sex differences in cortical activity and subjective pain disappeared when trait anxiety was controlled for. This means that stable predispositions to respond with heightened apprehension contribute to baseline pain sensitivity differences between the sexes. These results indicate that the modulatory effect of affect on pain-related brain processes may explain why men and women experience painful shocks so differently. In our study, the mediating role of anxiety on sex differences in pain was tested and confirmed using path analysis.

  14. [Comparison of the brain pharmacokinetics of nasal tetramethylpyrazine phosphate pH-sensitive in situ gel in normal rats and model rats].

    PubMed

    Liu, Hong-Wei; Yan, Yi-Lin; Zhou, Li-Ling

    2012-05-01

    The study is to investigate the brain pharmacokinetics change of nasal tetramethylpyrazine phosphate (TMPP) pH-sensitive in situ gel in normal and model rats. Acute cerebral ischemia rat model was successfully established by middle cerebral artery occlusion (MCAO) method. Both normal and model rats were given nasal TMPP pH-sensitive in situ gel (10 mg x kg(-1)). Perfusates of brain striatum area were collected at each time point by microdialysis. The content of TMPP was determined by HPLC. The pharmacokinetics parameters were calculated by Kinetica 4.4 software at each time point of the brain drug concentration. The main pharmacokinetics parameters of TMPP were fitted with compartments 2. After nasal TMPP pH-sensitive in situ gel the values of C(max) and AUC of both components in brain showed as follows: the value of model group > that of normal group. Significant difference can be observed in the process of brain pharmacokinetics in normal and model rats after giving nasal TMPP pH-sensitive in situ gel.

  15. Protein v. carbohydrate intake differentially affects liking- and wanting-related brain signalling.

    PubMed

    Born, Jurriaan M; Martens, Mieke J I; Lemmens, Sofie G T; Goebel, Rainer; Westerterp-Plantenga, Margriet S

    2013-01-28

    Extreme macronutrient intakes possibly lead to different brain signalling. The aim of the present study was to determine the effects of ingesting high-protein v. high-carbohydrate food on liking and wanting task-related brain signalling (TRS) and subsequent macronutrient intake. A total of thirty female subjects (21.6 (SD 2.2) years, BMI 25.0 (SD 3.7) kg/m²) completed four functional MRI scans: two fasted and two satiated on two different days. During the scans, subjects rated all food items for liking and wanting, thereby choosing the subsequent meal. The results show that high-protein (PROT) v. high-carbohydrate (CARB) conditions were generated using protein or carbohydrate drinks at the first meal. Energy intake and hunger were recorded. PROT (protein: 53.7 (SD 2.1) percentage of energy (En%); carbohydrate: 6.4 (SD 1.3) En%) and CARB conditions (protein: 11.8 (SD 0.6) En%; carbohydrate: 70.0 (SD 2.4) En%) were achieved during the first meal, while the second meals were not different between the conditions. Hunger, energy intake, and behavioural liking and wanting ratings were decreased after the first meal (P< 0.001). Comparing the first with the second meal, the macronutrient content changed: carbohydrate -26.9 En% in the CARB condition, protein -37.8 En% in the PROT condition. After the first meal in the CARB condition, wanting TRS was increased in the hypothalamus. After the first meal in the PROT condition, liking TRS was decreased in the putamen (P< 0.05). The change in energy intake from the first to the second meal was inversely related to the change in liking TRS in the striatum and hypothalamus in the CARB condition and positively related in the PROT condition (P< 0.05). In conclusion, wanting and liking TRS were affected differentially with a change in carbohydrate or protein intake, underscoring subsequent energy intake and shift in macronutrient composition.

  16. Ex-Vivo Characterization of Bioimpedance Spectroscopy of Normal, Ischemic and Hemorrhagic Rabbit Brain Tissue at Frequencies from 10 Hz to 1 MHz

    PubMed Central

    Yang, Lin; Zhang, Ge; Song, Jiali; Dai, Meng; Xu, Canhua; Dong, Xiuzhen; Fu, Feng

    2016-01-01

    Stroke is a severe cerebrovascular disease and is the second greatest cause of death worldwide. Because diagnostic tools (CT and MRI) to detect acute stroke cannot be used until the patient reaches the hospital setting, a portable diagnostic tool is urgently needed. Because biological tissues have different impedance spectra under normal physiological conditions and different pathological states, multi-frequency electrical impedance tomography (MFEIT) can potentially detect stroke. Accurate impedance spectra of normal brain tissue (gray and white matter) and stroke lesions (ischemic and hemorrhagic tissue) are important elements when studying stroke detection with MFEIT. To our knowledge, no study has comprehensively measured the impedance spectra of normal brain tissue and stroke lesions for the whole frequency range of 1 MHz within as short as possible an ex vivo time and using the same animal model. In this study, we established intracerebral hemorrhage and ischemic models in rabbits, then measured and analyzed the impedance spectra of normal brain tissue and stroke lesions ex vivo within 15 min after animal death at 10 Hz to 1 MHz. The results showed that the impedance spectra of stroke lesions significantly differed from those of normal brain tissue; the ratio of change in impedance of ischemic and hemorrhagic tissue with regard to frequency was distinct; and tissue type could be discriminated according to its impedance spectra. These findings further confirm the feasibility of detecting stroke with MFEIT and provide data supporting further study of MFEIT to detect stroke. PMID:27869707

  17. A Study of volumetric variations of basal nuclei in the normal human brain by magnetic resonance imaging.

    PubMed

    Elkattan, Amal; Mahdy, Amal; Eltomey, Mohamed; Ismail, Radwa

    2017-03-01

    Knowledge of the effects of healthy aging on brain structures is necessary to identify abnormal changes due to diseases. Many studies have demonstrated age-related volume changes in the brain using MRI. 60 healthy individuals who had normal MRI aged from 20 years to 80 years were examined and classified into three groups: Group I: 21 persons; nine males and 12 females aging between 20-39 years old. Group II: 22 persons; 11 males and 11 females aging between 40-59 years old. Group III: 17 persons; eight males and nine females aging between 60-80 years old. Volumetric analysis was done to evaluate the effect of age, gender and hemispheric difference in the caudate and putamen by the slicer 4.3.3.1 software using 3D T1-weighted images. Data were analyzed by student's unpaired t test, ANOVA and regression analysis. The volumes of the measured and corrected caudate nuclei and putamen significantly decreased with aging in males. There was a statistically insignificant relation between the age and the volume of the measured caudate nuclei and putamen in females but there was a statistically significant relation between the age and the corrected caudate nuclei and putamen. There was no significant difference on the caudate and putamen volumes between males and females. There was no significant difference between the right and left caudate nuclei volumes. There was a leftward asymmetry in the putamen volumes. The results can be considered as a base to track individual changes with time (aging and CNS diseases). Clin. Anat. 30:175-182, 2017. © 2017 Wiley Periodicals, Inc.

  18. Exposure to (12)C particles alters the normal dynamics of brain monoamine metabolism and behaviour in rats.

    PubMed

    Belov, Oleg V; Belokopytova, Ksenia V; Bazyan, Ara S; Kudrin, Vladimir S; Narkevich, Viktor B; Ivanov, Aleksandr A; Severiukhin, Yury S; Timoshenko, Gennady N; Krasavin, Eugene A

    2016-09-01

    Planning of the deep-space exploration missions raises a number of questions on the radiation protection of astronauts. One of the medical concerns is associated with exposure of a crew to highly energetic particles of galactic cosmic rays. Among many other health disorders, irradiation with these particles has a substantial impact on the central nervous system (CNS). Although radiation damage to CNS has been addressed extensively during the last years, the mechanisms underlying observed impairments remain mostly unknown. The present study reveals neurochemical and behavioural alterations induced in rats by 1Gy of 500MeV/u (12)C particles with a relatively moderate linear energy transfer (10.6keV/μm). It is found that exposure to carbon ions leads to significant modification of the normal monoamine metabolism dynamics as well as the locomotor, exploratory, and anxiety-like behaviours during a two-month period. The obtained results indicate an abnormal redistribution of monoamines and their metabolites in different brain regions after exposure. The most pronounced impairments are detected in the prefrontal cortex, nucleus accumbens, and hypothalamus that illustrate the sensitivity of these brain regions to densely ionizing radiations. It is also shown that exposure to (12)C particles enhances the anxiety in animals and accelerates the age-related reduction in their exploratory capability. The observed monoamine metabolism pattern may indicate the presence of certain compensatory mechanisms being induced in response to irradiation and capable of partial restoration of monoaminergic systems' functions. Overall, these findings support a possibility of CNS damage by space-born particles of a relatively moderate linear energy transfer.

  19. Physiological fluctuations in brain temperature as a factor affecting electrochemical evaluations of extracellular glutamate and glucose in behavioral experiments.

    PubMed

    Kiyatkin, Eugene A; Wakabayashi, Ken T; Lenoir, Magalie

    2013-05-15

    The rate of any chemical reaction or process occurring in the brain depends on temperature. While it is commonly believed that brain temperature is a stable, tightly regulated homeostatic parameter, it fluctuates within 1-4 °C following exposure to salient arousing stimuli and neuroactive drugs, and during different behaviors. These temperature fluctuations should affect neural activity and neural functions, but the extent of this influence on neurochemical measurements in brain tissue of freely moving animals remains unclear. In this Review, we present the results of amperometric evaluations of extracellular glutamate and glucose in awake, behaving rats and discuss how naturally occurring fluctuations in brain temperature affect these measurements. While this temperature contribution appears to be insignificant for glucose because its extracellular concentrations are large, it is a serious factor for electrochemical evaluations of glutamate, which is present in brain tissue at much lower levels, showing smaller phasic fluctuations. We further discuss experimental strategies for controlling the nonspecific chemical and physical contributions to electrochemical currents detected by enzyme-based biosensors to provide greater selectivity and reliability of neurochemical measurements in behaving animals.

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

    PubMed Central

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

    2016-01-01

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

  1. Gender, Race, and Diet Affect Platelet Function Tests in Normal Subjects Contributing to a High Rate of Abnormal Results

    PubMed Central

    Miller, Connie H.; Rice, Anne S.; Garrett, Katherine; Stein, Sidney F.

    2015-01-01

    Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients. PMID:24617520

  2. Effects of simplified ethanol-wet bonding technique on immediate bond strength with normal versus caries-affected dentin

    PubMed Central

    Aggarwal, Vivek; Singla, Mamta; Sharma, Ritu; Miglani, Sanjay; Bhasin, Saranjit Singh

    2016-01-01

    Aim: The aim of the present study was to evaluate whether the use of simplified ethanol-wet bonding (EWB) technique improved the immediate microtensile bond strength (μTBS) between resin composite and caries-affected dentin (CAD). Materials and Methods: Twenty-four extracted carious human permanent molars were sectioned to expose the carious lesion. The carious dentin was excavated until CAD was exposed. The samples were divided into two groups: water-wet bonding with Adper Scotchbond Multi-Purpose and a simplified EWB (three 100% ethanol applications for 30 s each), followed by application of an experimental hydrophobic primer and restoration. The samples were vertically sectioned to produce 1 mm × 1 mm thick slabs. The normal dentin (ND) slabs and CAD slabs were identified and were subjected to μTBS evaluation. Slabs from four teeth (two from each group) were evaluated under microscope. Data were analyzed using two-way ANOVA and post hoc Holm–Sidak test at P < 0.05. Results: EWB improved the μTBS in ND but not in CAD group. The dentinal tubules in CAD group showed sclerotic activity with minimal or no hybrid layer. Conclusions: Simplified ethanol bonding does not improve the bond strength in CAD. PMID:27656059

  3. Brain activation, affect, and aerobic exercise: an examination of both state-independent and state-dependent relationships.

    PubMed

    Petruzzello, S J; Tate, A K

    1997-09-01

    Resting electroencephalograph (EEG) asymmetry is a biological marker of the propensity to respond affectively to, and a measure of change in affect associated with, acute aerobic exercise. This study examined the EEG-affect-exercise relationship. Twenty participants performed each of three randomly assigned 30-min conditions: (a) a nonexercise control, (b) a cycling exercise at 55% VO2max, and (c) a cycling exercise at 70% VO2max. EEG and affect were assessed pre- and 0, 5, 10, 20, and 30 min postcondition. No significant results were seen in the control or 55% conditions. In the 70% exercise condition, greater relative left frontal activation preexercise predicted increased positive affect and reduced state anxiety postexercise. Participants (n = 7) with extreme relative left frontal activation postexercise reported concomitant decreases in anxiety, whereas participants (n = 7) with extreme relative right frontal activation postexercise reported increases in anxiety. These findings (a) replicate prior work, (b) suggest a dose-response intensity effect, and (c) support the idea that exercise is an emotion-eliciting event. Affective responses seem to be mediated in part by differential resting levels of activation in the anterior brain regions. Ongoing anterior brain activation reflected concurrent postexercise affect.

  4. Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat.

    PubMed

    Torres, Nimbe; Bautista, Claudia J; Tovar, Armando R; Ordáz, Guillermo; Rodríguez-Cruz, Maricela; Ortiz, Victor; Granados, Omar; Nathanielsz, Peter W; Larrea, Fernando; Zambrano, Elena

    2010-02-01

    Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

  5. Alpha-lipoic acid affects the oxidative stress in various brain structures in mice with methionine and choline deficiency

    PubMed Central

    Veskovic, Milena; Mladenovic, Dusan; Jorgacevic, Bojan; Stevanovic, Ivana; de Luka, Silvio

    2015-01-01

    Deficiency in methionine or choline can induce oxidative stress in various organs such as liver, kidney, heart, and brain. This study was to examine the effects of alpha-lipoic acid (LA) on oxidative stress induced by methionine and choline deficiency (MCD) in several brain structures. Male mice C57BL/6 (n = 28) were divided into four groups: (1) control – continuously fed with standard chow; (2) LA – fed with standard chow and receiving LA; (3) MCD2 – fed with MCD diet for two weeks, and (4) MCD2+LA – fed with MCD diet for two weeks and receiving LA (100 mg/kg/day intraperitonealy [i.p.]). Brain tissue (cortex, hypothalamus, striatum and hippocampus) was taken for determination of oxidative stress parameters. MCD diet induced a significant increase in malondialdehyde and NOx concentration in all brain regions, while LA restored their content to normal values. Similar to this, in MCD2 group, activity of total SOD, MnSOD, and Cu/ZnSOD was reduced by MCD diet, while LA treatment improved their activities in all brain structures. Besides, in MCD2 group a decrease in catalase activity in cortex and GSH content in hypothalamus was evident, while LA treatment induced an increase in catalase activity in cortex and striatum and GSH content in hypothalamus. LA treatment can significantly reduce lipid peroxidation and nitrosative stress, caused by MCD diet, in all brain regions by restoring antioxidant enzymes activities, predominantly total SOD, MnSOD, and Cu/ZnSOD, and to a lesser extent by modulating catalase activity and GSH content. LA supplementation may be used in order to prevent brain oxidative injury induced by methionine and choline deficiency. PMID:25193852

  6. Comparison of blood brain barrier permeability in normal and ovariectomized female rats that demonstrate right or left paw preference.

    PubMed

    Kutlu, N; Mutlu, F; Vural, K; Cezayirli, E

    2012-11-01

    We explored the relations among paw preference, cerebral asymmetry and asymmetrical disruption of blood-brain barrier (BBB) permeability in normal and ovariectomized female rats with known paw preference. A high dose of pentylenetetrazol was used to disrupt the BBB and induce acute hypertension. To determine the areas of macroscopic infarct, samples were stained with 2,3,5-triphenyltetrazolium chloride. Histological staining techniques were used to show the areas of infarct microscopically on paraffin sections. Sixty-two percent of the rats demonstrated right paw preference, 24% demonstrated left paw preference and 14% were ambidextrous. Areas of infarct, which indicated destruction of the BBB, were determined microscopically and macroscopically in rats that demonstrated right and left paw preference. We found a relation between permeability of the BBB and paw preference. There may be a relation between paw preference, cerebral asymmetry and asymmetrical destruction of the BBB in rats. Asymmetrical destruction of the BBB in experimental rats was similar to the control group, which had asymmetrically disrupted BBB with respect to paw preference. Like the control rats, asymmetrical areas of infarct consistent with cerebral asymmetry were observed in ovariectomized rats.

  7. Longitudinal Assessments of Normal and Perilesional Tissues in Focal Brain Ischemia and Partial Optic Nerve Injury with Manganese-enhanced MRI

    PubMed Central

    Chan, Kevin C.; Zhou, Iris Y.; Liu, Stanley S.; van der Merwe, Yolandi; Fan, Shu-Juan; Hung, Victor K.; Chung, Sookja K.; Wu, Wu-tian; So, Kwok-fai; Wu, Ed X.

    2017-01-01

    Although manganese (Mn) can enhance brain tissues for improving magnetic resonance imaging (MRI) assessments, the underlying neural mechanisms of Mn detection remain unclear. In this study, we used Mn-enhanced MRI to test the hypothesis that different Mn entry routes and spatiotemporal Mn distributions can reflect different mechanisms of neural circuitry and neurodegeneration in normal and injured brains. Upon systemic administration, exogenous Mn exhibited varying transport rates and continuous redistribution across healthy rodent brain nuclei over a 2-week timeframe, whereas in rodents following photothrombotic cortical injury, transient middle cerebral artery occlusion, or neonatal hypoxic-ischemic brain injury, Mn preferentially accumulated in perilesional tissues expressing gliosis or oxidative stress within days. Intravitreal Mn administration to healthy rodents not only allowed tracing of primary visual pathways, but also enhanced the hippocampus and medial amygdala within a day, whereas partial transection of the optic nerve led to MRI detection of degrading anterograde Mn transport at the primary injury site and the perilesional tissues secondarily over 6 weeks. Taken together, our results indicate the different Mn transport dynamics across widespread projections in normal and diseased brains. Particularly, perilesional brain tissues may attract abnormal Mn accumulation and gradually reduce anterograde Mn transport via specific Mn entry routes. PMID:28230106

  8. Normal aging affects movement execution but not visual motion working memory and decision-making delay during cue-dependent memory-based smooth-pursuit.

    PubMed

    Fukushima, Kikuro; Barnes, Graham R; Ito, Norie; Olley, Peter M; Warabi, Tateo

    2014-07-01

    Aging affects virtually all functions including sensory/motor and cognitive activities. While retinal image motion is the primary input for smooth-pursuit, its efficiency/accuracy depends on cognitive processes. Elderly subjects exhibit gain decrease during initial and steady-state pursuit, but reports on latencies are conflicting. Using a cue-dependent memory-based smooth-pursuit task, we identified important extra-retinal mechanisms for initial pursuit in young adults including cue information priming and extra-retinal drive components (Ito et al. in Exp Brain Res 229:23-35, 2013). We examined aging effects on parameters for smooth-pursuit using the same tasks. Elderly subjects were tested during three task conditions as previously described: memory-based pursuit, simple ramp-pursuit just to follow motion of a single spot, and popping-out of the correct spot during memory-based pursuit to enhance retinal image motion. Simple ramp-pursuit was used as a task that did not require visual motion working memory. To clarify aging effects, we then compared the results with the previous young subject data. During memory-based pursuit, elderly subjects exhibited normal working memory of cue information. Most movement-parameters including pursuit latencies differed significantly between memory-based pursuit and simple ramp-pursuit and also between young and elderly subjects. Popping-out of the correct spot motion was ineffective for enhancing initial pursuit in elderly subjects. However, the latency difference between memory-based pursuit and simple ramp-pursuit in individual subjects, which includes decision-making delay in the memory task, was similar between the two groups. Our results suggest that smooth-pursuit latencies depend on task conditions and that, although the extra-retinal mechanisms were functional for initial pursuit in elderly subjects, they were less effective.

  9. Quantitative volumetric analysis of the optic radiation in the normal human brain using diffusion tensor magnetic resonance imaging-based tractography

    PubMed Central

    Lee, Dong-Hoon; Park, Ji-Won; Hong, Cheol-Pyo

    2014-01-01

    To attain the volumetric information of the optic radiation in normal human brains, we performed diffusion tensor imaging examination in 13 healthy volunteers. Simultaneously, we used a brain normalization method to reduce individual brain variation and increase the accuracy of volumetric information analysis. In addition, tractography-based group mapping method was also used to investigate the probability and distribution of the optic radiation pathways. Our results showed that the measured optic radiation fiber tract volume was a range of about 0.16% and that the fractional anisotropy value was about 0.53. Moreover, the optic radiation probability fiber pathway that was determined with diffusion tensor tractography-based group mapping was able to detect the location relatively accurately. We believe that our methods and results are helpful in the study of optic radiation fiber tract information. PMID:25206813

  10. Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake

    PubMed Central

    Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schiöth, H B

    2016-01-01

    Background: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals—that is, resting-state brain activity—in the context of food intake are, however, less well studied. Objective: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). Methods: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m−2) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m−2), both before and 30 min after consumption of a standardized meal (~260 kcal). Results: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups. Conclusion: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans. PMID:27349694

  11. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    PubMed

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  12. ABCB1 (MDR1)-type P-glycoproteins at the blood-brain barrier modulate the activity of the hypothalamic-pituitary-adrenocortical system: implications for affective disorder.

    PubMed

    Müller, Marianne B; Keck, Martin E; Binder, Elisabeth B; Kresse, Adelheid E; Hagemeyer, Thomas P; Landgraf, Rainer; Holsboer, Florian; Uhr, Manfred

    2003-11-01

    Multidrug-resistance gene 1-type P-glycoproteins (ABCB1-type P-gps) protect the brain against the accumulation of many toxic xenobiotics and drugs. We recently could show that the access of the endogenous glucocorticoids corticosterone and cortisol to the brain are regulated by ABCB1-type P-gps in vivo. ABCB1-type P-gp function, therefore, is likely to exert a profound influence on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Hyperactivity of the HPA system is frequently observed in human affective disorder, and a considerable amount of evidence has been accumulated suggesting that normalization of the HPA system might be the final step necessary for stable remission of the disease. To examine whether blood-brain barrier (BBB) function influences neuroendocrine regulation, we investigated HPA system activity in abcb1ab (-/-) mice under basal conditions and following stress. Abcb1ab (-/-) mice showed consistently lower plasma ACTH levels and lower evening plasma corticosterone levels. CRH mRNA expression in the hypothalamic paraventricular nucleus was decreased and pituitary POMC mRNA expressing cells were significantly reduced in number in abcb1ab (-/-) mutants; however, they showed a normal activation of the HPA system following CRH stimulation. Lower doses of dexamethasone were required to suppress plasma corticosterone levels in mutants. Our data thus provide evidence for a sustained suppression of the HPA system at the hypothalamic level in abcb1ab (-/-) mice, suggesting that BBB function significantly regulates HPA system activity. Whether naturally occurring polymorphisms in the human ABCB1 gene might result in persistent changes in the responsiveness and regulation of the HPA system will be the subject of future investigations, correlating both genetic information with individual characteristics of the neuroendocrine phenotype.

  13. Pericyte abundance affects sucrose permeability in cultures of rat brain microvascular endothelial cells.

    PubMed

    Parkinson, Fiona E; Hacking, Cindy

    2005-07-05

    The blood-brain barrier is a physical and metabolic barrier that restricts diffusion of blood-borne substances into brain. In vitro models of the blood-brain barrier are used to characterize this structure, examine mechanisms of damage and repair and measure permeability of test substances. The core component of in vitro models of the blood-brain barrier is brain microvascular endothelial cells. We cultured rat brain microvascular endothelial cells (RBMEC) from isolated rat cortex microvessels. After 2-14 days in vitro (DIV), immunohistochemistry of these cells showed strong labeling for zona occludens 1 (ZO-1), a tight junction protein expressed in endothelial cells. Pericytes were also present in these cultures, as determined by expression of alpha-actin. The present study was performed to test different cell isolation methods and to compare the resulting cell cultures for abundance of pericytes and for blood-brain barrier function, as assessed by 14C-sucrose flux. Two purification strategies were used. First, microvessels were preabsorbed onto uncoated plastic for 4 h, then unattached microvessels were transferred to coated culture ware. Second, microvessels were incubated with an antibody to platelet-endothelial cell adhesion molecule 1 (PECAM-1; CD31) precoupled to magnetic beads, and a magnetic separation procedure was performed. Our results indicate that immunopurification, but not preadsorption, was an effective method to purify microvessels and reduce pericyte abundance in the resulting cultures. This purification significantly reduced 14C-sucrose fluxes across cell monolayers. These data indicate that pericytes can interfere with the development of blood-brain barrier properties in in vitro models that utilize primary cultures of RBMECs.

  14. Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.

    PubMed

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

    2010-09-09

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

  15. One-year high fat diet affects muscle-but not brain mitochondria.

    PubMed

    Jørgensen, Tenna; Grunnet, Niels; Quistorff, Bjørn

    2015-06-01

    It is well known that few weeks of high fat (HF) diet may induce metabolic disturbances and mitochondrial dysfunction in skeletal muscle. However, little is known about the effects of long-term HF exposure and effects on brain mitochondria are unknown. Wistar rats were fed either chow (13E% fat) or HF diet (60E% fat) for 1 year. The HF animals developed obesity, dyslipidemia, insulin resistance, and dysfunction of isolated skeletal muscle mitochondria: state 3 and state 4 were 30% to 50% increased (P<0.058) with palmitoyl carnitine (PC), while there was no effect with pyruvate as substrate. Adding also succinate in state 3 resulted in a higher substrate control ratio (SCR) with PC, but a lower SCR with pyruvate (P<0.05). The P/O2 ratio was lower with PC (P<0.004). However, similar tests on isolated brain mitochondria from the same animal showed no changes with the substrates relevant for brain (pyruvate and 3-hydroxybutyrate). Thus, long-term HF diet was associated with obesity, dyslipidemia, insulin resistance, and significantly altered mitochondrial function in skeletal muscle. Yet, brain mitochondria were unaffected. We suggest that the relative isolation of the brain due to the blood-brain barrier may play a role in this strikingly different phenotype of mitochondria from the two tissues of the same animal.

  16. Tunes stuck in your brain: The frequency and affective evaluation of involuntary musical imagery correlate with cortical structure.

    PubMed

    Farrugia, Nicolas; Jakubowski, Kelly; Cusack, Rhodri; Stewart, Lauren

    2015-09-01

    Recent years have seen a growing interest in the neuroscience of spontaneous cognition. One form of such cognition is involuntary musical imagery (INMI), the non-pathological and everyday experience of having music in one's head, in the absence of an external stimulus. In this study, aspects of INMI, including frequency and affective evaluation, were measured by self-report in 44 subjects and related to variation in brain structure in these individuals. Frequency of INMI was related to cortical thickness in regions of right frontal and temporal cortices as well as the anterior cingulate and left angular gyrus. Affective aspects of INMI, namely the extent to which subjects wished to suppress INMI or considered them helpful, were related to gray matter volume in right temporopolar and parahippocampal cortices respectively. These results provide the first evidence that INMI is a common internal experience recruiting brain networks involved in perception, emotions, memory and spontaneous thoughts.

  17. Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training.

    PubMed

    Koba, Satoshi; Hisatome, Ichiro; Watanabe, Tatsuo

    2014-09-01

    Sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command-elicited sympathoexcitation, and that exercise training in CHF suppresses central command-elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham-operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation-elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation-elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.

  18. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

    PubMed Central

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

    2013-01-01

    It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-13C3]heptanoate was examined in the normal mouse brain and in G1D by 13C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in 13C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and 13C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. PMID:23072752

  19. Vowels and Consonants in the Brain: Evidence from Magnetoencephalographic Studies on the N1m in Normal-Hearing Listeners

    PubMed Central

    Manca, Anna Dora; Grimaldi, Mirko

    2016-01-01

    Speech sound perception is one of the most fascinating tasks performed by the human brain. It involves a mapping from continuous acoustic waveforms onto the discrete phonological units computed to store words in the mental lexicon. In this article, we review the magnetoencephalographic studies that have explored the timing and morphology of the N1m component to investigate how vowels and consonants are computed and represented within the auditory cortex. The neurons that are involved in the N1m act to construct a sensory memory of the stimulus due to spatially and temporally distributed activation patterns within the auditory cortex. Indeed, localization of auditory fields maps in animals and humans suggested two levels of sound coding, a tonotopy dimension for spectral properties and a tonochrony dimension for temporal properties of sounds. When the stimulus is a complex speech sound, tonotopy and tonochrony data may give important information to assess whether the speech sound parsing and decoding are generated by pure bottom-up reflection of acoustic differences or whether they are additionally affected by top-down processes related to phonological categories. Hints supporting pure bottom-up processing coexist with hints supporting top-down abstract phoneme representation. Actually, N1m data (amplitude, latency, source generators, and hemispheric distribution) are limited and do not help to disentangle the issue. The nature of these limitations is discussed. Moreover, neurophysiological studies on animals and neuroimaging studies on humans have been taken into consideration. We compare also the N1m findings with the investigation of the magnetic mismatch negativity (MMNm) component and with the analogous electrical components, the N1 and the MMN. We conclude that N1 seems more sensitive to capture lateralization and hierarchical processes than N1m, although the data are very preliminary. Finally, we suggest that MEG data should be integrated with EEG data in the

  20. Vowels and Consonants in the Brain: Evidence from Magnetoencephalographic Studies on the N1m in Normal-Hearing Listeners.

    PubMed

    Manca, Anna Dora; Grimaldi, Mirko

    2016-01-01

    Speech sound perception is one of the most fascinating tasks performed by the human brain. It involves a mapping from continuous acoustic waveforms onto the discrete phonological units computed to store words in the mental lexicon. In this article, we review the magnetoencephalographic studies that have explored the timing and morphology of the N1m component to investigate how vowels and consonants are computed and represented within the auditory cortex. The neurons that are involved in the N1m act to construct a sensory memory of the stimulus due to spatially and temporally distributed activation patterns within the auditory cortex. Indeed, localization of auditory fields maps in animals and humans suggested two levels of sound coding, a tonotopy dimension for spectral properties and a tonochrony dimension for temporal properties of sounds. When the stimulus is a complex speech sound, tonotopy and tonochrony data may give important information to assess whether the speech sound parsing and decoding are generated by pure bottom-up reflection of acoustic differences or whether they are additionally affected by top-down processes related to phonological categories. Hints supporting pure bottom-up processing coexist with hints supporting top-down abstract phoneme representation. Actually, N1m data (amplitude, latency, source generators, and hemispheric distribution) are limited and do not help to disentangle the issue. The nature of these limitations is discussed. Moreover, neurophysiological studies on animals and neuroimaging studies on humans have been taken into consideration. We compare also the N1m findings with the investigation of the magnetic mismatch negativity (MMNm) component and with the analogous electrical components, the N1 and the MMN. We conclude that N1 seems more sensitive to capture lateralization and hierarchical processes than N1m, although the data are very preliminary. Finally, we suggest that MEG data should be integrated with EEG data in the

  1. GABA and Glutamate Pathways Are Spatially and Developmentally Affected in the Brain of Mecp2-Deficient Mice

    PubMed Central

    Matagne, Valérie; Ghata, Adeline; Villard, Laurent; Roux, Jean-Christophe

    2014-01-01

    Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the postnatal brain development. Dysfunctions in the GABAergic and glutamatergic systems have been implicated in the neuropathology of RTT and a disruption of the balance between excitation and inhibition, together with a perturbation of the electrophysiological properties of GABA and glutamate neurons, were reported in the brain of the Mecp2-deficient mouse. However, to date, the extent and the nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain are unclear. In order to better characterize these deficits, we simultaneously analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different ages (P35 and P55) and in several brain areas. We used a multilevel approach including the quantification of GABA and glutamate levels, as well as the quantification of the mRNA and protein expression levels of key genes involved in the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient mice displayed regional- and age-dependent variations in the GABA pathway and, to a lesser extent, in the glutamate pathway. The implication of the GABA pathway in the RTT neuropathology was further confirmed using an in vivo treatment with a GABA reuptake inhibitor that significantly improved the lifespan of Mecp2-deficient mice. Our results confirm that RTT mouse present a deficit in the GABAergic pathway and suggest that GABAergic modulators could be interesting therapeutic agents for this severe neurological disorder. PMID:24667344

  2. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    PubMed Central

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  3. Melatonin affects the order, dynamics and hydration of brain membrane lipids

    NASA Astrophysics Data System (ADS)

    Akkas, Sara B.; Inci, Servet; Zorlu, Faruk; Severcan, Feride

    2007-05-01

    The brain is especially susceptible to free radical attack since it is rich in polyunsaturated fatty acids and consumes very high amounts of oxygen. Melatonin is a non-enzymatic amphiphilic antioxidant hormone that is widely used in medicine for protective and treatment purposes in cases of oxidative stress. In the present work, the effects of the clinically used dose of melatonin (a single intraperitoneal dose of 100 mg/kg) on rat brain homogenate were investigated as a function of temperature using Fourier transform infrared spectroscopy. The results showed that the lipid to protein ratio decreases in the melatonin treated brain samples. Moreover, it is revealed that melatonin disorders and decreases the dynamics of lipids and induces a strengthening in the hydrogen bonding between the functional groups of both melatonin and the polar parts of lipids and/or water at physiological temperatures.

  4. Normal pressure hydrocephalus (NPH)

    MedlinePlus

    ... cerebrospinal fluid (CSF) in the brain that affects brain function. However, the pressure of the fluid is usually ... shunt that does not work well) Loss of brain function ( dementia ) that becomes worse over time Injury from ...

  5. Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis?

    PubMed

    Laugero, K D; Bell, M E; Bhatnagar, S; Soriano, L; Dallman, M F

    2001-07-01

    Both CRF and norepinephrine (NE) inhibit food intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH. Here, we show that ADX (but not sham-ADX) rats prefer to consume significantly more sucrose than saccharin. Voluntary ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to normal. Our results suggest that the brains of ADX rats, cued by sucrose energy (but not by nonnutritive saccharin) maintain normal activity in systems that regulate neuroendocrine (hypothalamic-pituitary-adrenal), behavioral (feeding), and metabolic functions (fat deposition). We conclude that because sucrose ingestion, like glucocorticoid replacement, normalizes energetic and neuromodulatory effects of ADX, many of the actions of the steroids on the central nervous system under basal conditions may be indirect and mediated by signals that result from the metabolic effects of adrenal steroids.

  6. Brain-Computer Interface Training after Stroke Affects Patterns of Brain-Behavior Relationships in Corticospinal Motor Fibers.

    PubMed

    Young, Brittany M; Stamm, Julie M; Song, Jie; Remsik, Alexander B; Nair, Veena A; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2016-01-01

    Background: Brain-computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective: This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods: Stroke patients (n = 19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results: No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p < 0.05 corrected. Conclusion: These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke.

  7. Motivation and semantic context affect brain error-monitoring activity: an event-related brain potentials study.

    PubMed

    Ganushchak, Lesya Y; Schiller, Niels O

    2008-01-01

    During speech production, we continuously monitor what we say. In situations in which speech errors potentially have more severe consequences, e.g. during a public presentation, our verbal self-monitoring system may pay special attention to prevent errors than in situations in which speech errors are more acceptable, such as a casual conversation. In an event-related potential study, we investigated whether or not motivation affected participants' performance using a picture naming task in a semantic blocking paradigm. Semantic context of to-be-named pictures was manipulated; blocks were semantically related (e.g., cat, dog, horse, etc.) or semantically unrelated (e.g., cat, table, flute, etc.). Motivation was manipulated independently by monetary reward. The motivation manipulation did not affect error rate during picture naming. However, the high-motivation condition yielded increased amplitude and latency values of the error-related negativity (ERN) compared to the low-motivation condition, presumably indicating higher monitoring activity. Furthermore, participants showed semantic interference effects in reaction times and error rates. The ERN amplitude was also larger during semantically related than unrelated blocks, presumably indicating that semantic relatedness induces more conflict between possible verbal responses.

  8. Differences in brain functional connectivity at resting-state in neonates born to healthy obese or normal-weight mothers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lo...

  9. Brain activation related to affective dimension during thermal stimulation in humans: a functional magnetic resonance imaging study.

    PubMed

    Sung, Eun-Jung; Yoo, Seung-Schik; Yoon, Hyo Woon; Oh, Sung-Suk; Han, Yeji; Park, Hyun Wook

    2007-07-01

    The aim of this study was to identify the activated brain region that is involved with the affective dimension of thermal stimulation (not pain, but innocuous warming) using functional MR imaging. Twelve healthy, right-handed male subjects participated in the study. Thermal stimulation with two different temperatures of 41 degrees C and 34 degrees C was applied to the subjects using a fomentation pack, wrapped around the right lower leg of each subject. On the basis of the subjects' responses after the scanning sessions, the authors were able to observe that the subjects felt "warm" and "slightly pleasant and comfortable" under the 41 degrees C condition. The experimental results indicated that warm stimulation produced a significant increase of activation compared to thermal neutral stimulation in various regions such as contralateral insular, ipsilateral cerebellum, ipsilateral putamen, contralateral middle frontal gyrus, ipsilateral inferior frontal gyrus, contralateral postcentral gyrus, and contralateral paracentral lobule. The activated regions are known to be related to thermal sensory, affective/emotional awareness, cognitive functions, sensory-discrimination, and emotion/affective processing, and so on. These results suggest that an appropriate thermal stimulation can produce a positive emotion and activate emotion/affect related regions of the brain.

  10. Sisters and Brothers, Brothers and Sisters in the Family Affected by Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Pieper, Betty

    This report is based on a qualitative research study which utilized a nominal group process to identify major life stressors for parents of children with traumatic brain injuries (TBI). It focuses first on effects of TBI on siblings and then on effective interventions. The first section uses quotes from participating parents to identify their…

  11. Social Brain Development and the Affective Consequences of Ostracism in Adolescence

    ERIC Educational Resources Information Center

    Sebastian, Catherine; Viding, Essi; Williams, Kipling D.; Blakemore, Sarah-Jayne

    2010-01-01

    Recent structural and functional imaging studies have provided evidence for continued development of brain regions involved in social cognition during adolescence. In this paper, we review this rapidly expanding area of neuroscience and describe models of neurocognitive development that have emerged recently. One implication of these models is…

  12. Prion Protein M129V Polymorphism Affects Retrieval-Related Brain Activity

    ERIC Educational Resources Information Center

    Buchmann, Andreas; Mondadori, Christian R. A.; Hanggi, Jurgen; Aerni, Amanda; Vrticka, Pascal; Luechinger, Roger; Boesiger, Peter; Hock, Christoph; Nitsch, Roger M.; de Quervain, Dominique J.-F.; Papassotiropoulos, Andreas; Henke, Katharina

    2008-01-01

    The prion protein Met129Val polymorphism has recently been related to human long-term memory with carriers of either the 129[superscript MM] or the 129[superscript MV] genotype recalling 17% more words than 129[superscript VV] carriers at 24 h following learning. Here, we sampled genotype differences in retrieval-related brain activity at 30 min…

  13. Social Comparison Affects Brain Responses to Fairness in Asset Division: An ERP Study with the Ultimatum Game

    PubMed Central

    Wu, Yin; Zhou, Yuqin; van Dijk, Eric; Leliveld, Marijke C.; Zhou, Xiaolin

    2011-01-01

    Previous studies have shown that social comparison influences individual’s fairness consideration and other-regarding behavior. However, it is not clear how social comparison affects the brain activity in evaluating fairness during asset distribution. In this study, participants, acting as recipients in the ultimatum game, were informed not only of offers to themselves but also of the average amount of offers in other allocator–recipient dyads. Behavioral results showed that the participants were more likely to reject division schemes when they were offered less than the other recipients, especially when the offers were highly unequal. Event-related brain potentials recorded from the participants showed that highly unequal offers elicited more negative-going medial frontal negativity than moderately unequal offers in an early time window (270–360 ms) and this effect was not significantly modulated by social comparison. In a later time window (450–650 ms), however, the late positive potential (LPP) was more positive for moderately unequal offers than for highly unequal offers when the other recipients were offered less than the participants, whereas this distinction disappeared when the other recipients were offered the same as or more than the participants. These findings suggest that the brain activity in evaluating fairness in asset division entails both an earlier (semi-) automatic process in which the brain responds to fairness at an abstract level and a later appraisal process in which factors related to social comparison and fairness norms come into play. PMID:22087088

  14. Pregnancy affects FOS rhythms in brain regions regulating sleep/wake state and body temperature in rats.

    PubMed

    Schrader, Jessica A; Smale, Laura; Nunez, Antonio A

    2012-10-22

    Circadian rhythms in behavior and physiology change substantially as female mammals undergo the transition from a non-pregnant to a pregnant state. Here, we examined the possibility that site-specific changes in brain regions known to regulate the sleep/wake cycle and body temperature might reflect altered rhythms in these overt functions. Specifically, we compared daily patterns of immunoreactive FOS in early pregnant and diestrous rats in the medial septum (MS), vertical and horizontal diagonal bands of Broca (VDB and HDB), perifornical lateral hypothalamus (LH), and ventrolateral, medial, and median preoptic areas (VLPO, MPA, and MnPO, respectively). In the pregnant animals, FOS expression was reduced and the daily rhythms of expression were lost or attenuated in the MS, VDB, and LH, areas known to support wakefulness, and in the MPA, a brain region that may coordinate sleep/wake patterns with temperature changes. However, despite the well-documented differences in sleep patterns between diestrous and pregnant rats, reproductive state did not affect FOS expression in the VLPO or MnPO, two brain regions in which FOS expression usually correlates with sleep. These data indicate that plasticity in sleep/wake patterns during early pregnancy may be driven by a reduction in wakefulness-promotion by the brain, rather than by an increase in sleep drive.

  15. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    PubMed

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

  16. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    PubMed

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  17. Brain activation and defensive response mobilization during sustained exposure to phobia-related and other affective pictures in spider phobia.

    PubMed

    Wendt, Julia; Lotze, Martin; Weike, Almut I; Hosten, Norbert; Hamm, Alfons O

    2008-03-01

    This study explored defensive response mobilization as well as fMRI responses during sustained exposure to phobia-relevant stimuli. To test the specificity of affective physiology and brain activation, neutral and other affective stimuli were included. Phobia-specific startle potentiation was maintained and autonomic responses even increased during sustained phobic stimulation. Viewing of spider pictures also resulted in increased activation of the amygdala in spider-phobic participants. This effect, however, was not fear specific because other affective materials evoked comparable signal strength in the amygdala. In contrast, insula activation was specifically increased during sustained phobic exposure in phobic volunteers. These data suggest that the activation of the amygdala in fMRI studies primarily indexes the detection of motivationally relevant stimuli whereas the insula might be more specifically linked to defensive response mobilization.

  18. Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination.

    PubMed

    Kirk, John; Plumb, Jonnie; Mirakhur, Meenakshi; McQuaid, Stephen

    2003-10-01

    Blood-brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal-appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls. Using single and double immunofluorescence and confocal microscopy, the TJ-associated protein zonula occludens-1 (ZO-1) was examined across lesion types and tissue categories, and in relation to fibrinogen leakage. Confocal image data sets were analysed for 2198 MS and 1062 control vessels. Significant differences in the incidence of TJ abnormalities were detected between the different lesion types in MS and between MS and control white matter. These were frequent in oil-red O (ORO)(+) active plaques, affecting 42% of vessel segments, but less frequent in ORO(-) inactive plaques (23%), NAWM (13%), and normal (3.7%) and neurological controls (8%). A similar pattern was found irrespective of the vessel size, supporting a causal role for diffusible inflammatory mediators. In both NAWM and inactive lesions, dual labelling showed that vessels with the most TJ abnormality also showed most fibrinogen leakage. This was even more pronounced in active lesions, where 41% of vessels in the highest grade for TJ alteration showed severe leakage. It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage. TJ abnormality and BBB leakage in inactive lesions suggests either failure of TJ repair or a continuing pathological process. In NAWM, it suggests either pre-lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease-modifying therapy.

  19. Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

    PubMed

    Laing, Katharine R; Mitchell, David; Wersching, Heike; Czira, Maria E; Berger, Klaus; Baune, Bernhard T

    2012-08-01

    Cognitive aging processes are underpinned by multiple processes including genetic factors. The brain-derived neurotrophic factor (BDNF) has been suggested to be involved in age-related cognitive decline in otherwise healthy individuals. The gender-specific role of the BDNF gene in cognitive aging remains unclear. The identification of genetic biomarkers might be a useful approach to identify individuals at risk of cognitive decline during healthy aging processes. The aim of this study was to investigate the associations between three single-nucleotide polymorphisms (SNPs) in the BDNF gene and domains of cognitive functioning in normal cognitive aging. The sample, comprising 369 participants (M = 72.7 years, SD = 4.45 years), completed an extensive neuropsychological test battery measuring memory, motor function, and perceptual speed. The relationships between the SNPs rs6265, rs7103411, and rs7124442 and cognitive domains were examined. While significant main effects of BDNF SNPs on cognitive function were found for the association between rs7103411 and memory performance, gender-specific analyses revealed for females significant main effects of rs7103411 for memory and of rs6265 for perceptual speed independent of the APOE*E4 status and education. The finding for the association between rs6265 and perceptual speed in females remained significant after Bonferroni correction for multiple comparisons. None of the analyses showed significant results for males. This study is the first to implicate that the SNPs rs6265 and rs7103411 affect cognitive function in the elderly in a gender-specific way.

  20. Changing facial affect recognition in schizophrenia: effects of training on brain dynamics.

    PubMed

    Popova, Petia; Popov, Tzvetan G; Wienbruch, Christian; Carolus, Almut M; Miller, Gregory A; Rockstroh, Brigitte S

    2014-01-01

    Deficits in social cognition including facial affect recognition and their detrimental effects on functional outcome are well established in schizophrenia. Structured training can have substantial effects on social cognitive measures including facial affect recognition. Elucidating training effects on cortical mechanisms involved in facial affect recognition may identify causes of dysfunctional facial affect recognition in schizophrenia and foster remediation strategies. In the present study, 57 schizophrenia patients were randomly assigned to (a) computer-based facial affect training that focused on affect discrimination and working memory in 20 daily 1-hour sessions, (b) similarly intense, targeted cognitive training on auditory-verbal discrimination and working memory, or (c) treatment as usual. Neuromagnetic activity was measured before and after training during a dynamic facial affect recognition task (5 s videos showing human faces gradually changing from neutral to fear or to happy expressions). Effects on 10-13 Hz (alpha) power during the transition from neutral to emotional expressions were assessed via MEG based on previous findings that alpha power increase is related to facial affect recognition and is smaller in schizophrenia than in healthy subjects. Targeted affect training improved overt performance on the training tasks. Moreover, alpha power increase during the dynamic facial affect recognition task was larger after affect training than after treatment-as-usual, though similar to that after targeted perceptual-cognitive training, indicating somewhat nonspecific benefits. Alpha power modulation was unrelated to general neuropsychological test performance, which improved in all groups. Results suggest that specific neural processes supporting facial affect recognition, evident in oscillatory phenomena, are modifiable. This should be considered when developing remediation strategies targeting social cognition in schizophrenia.

  1. In situ demonstration of Fluoro-Turquoise conjugated gelatin for visualizing brain vasculature and endothelial cells and their characterization in normal and kainic acid exposed animals.

    PubMed

    Sarkar, Sumit; Raymick, James; Paule, Merle G; Schmued, Larry

    2013-10-15

    The present study describes a new method for the visualization of the vasculature lumen and endothelial cells and characterizes their morphology in the brains of normal and kainic acid (KA) treated rats. Herein, labeling was accomplished using Fluoro-Turquoise (FT), a novel reactive blue fluorochrome conjugated to gelatin. Strong blue fluorescence was observed throughout the brain vasculature following intra-cardiac perfusion with FT-gel in normal animals. However, in the brains of KA treated rats (hippocampus, midline and ventral thalamus, piriform cortex), the vascular lumen was typically constricted, sclerotic and only faintly stained. The advantages of FT-gel over other markers can be attributed to its unique chemical and spectral properties. Specifically, Fluoro-Turquoise is a very bright blue UV excitable dye that does not bleed through when visualized using other filters, making it ideal for multiple immunofluorescent labeling studies. Its brightness at low magnification also makes it ideal for low magnification whole brain imaging. Compared to alternative techniques for visualizing blood vessels, such as India ink, fluorescent dye-conjugated dextran, the corrosion technique, endothelial cell markers and lectins, the present method results in excellent visualization of blood vessels.

  2. Alzheimer's disease: relevant molecular and physiopathological events affecting amyloid-β brain balance and the putative role of PPARs.

    PubMed

    Zolezzi, Juan M; Bastías-Candia, Sussy; Santos, Manuel J; Inestrosa, Nibaldo C

    2014-01-01

    Alzheimer's disease (AD) is the most common form of age-related dementia. With the expected aging of the human population, the estimated morbidity of AD suggests a critical upcoming health problem. Several lines of research are focused on understanding AD pathophysiology, and although the etiology of the disease remains a matter of intense debate, increased brain levels of amyloid-β (Aβ) appear to be a critical event in triggering a wide range of molecular alterations leading to AD. It has become evident in recent years that an altered balance between production and clearance is responsible for the accumulation of brain Aβ. Moreover, Aβ clearance is a complex event that involves more than neurons and microglia. The status of the blood-brain barrier (BBB) and choroid plexus, along with hepatic functionality, should be considered when Aβ balance is addressed. Furthermore, it has been proposed that exposure to sub-toxic concentrations of metals, such as copper, could both directly affect these secondary structures and act as a seeding or nucleation core that facilitates Aβ aggregation. Recently, we have addressed peroxisomal proliferator-activated receptors (PPARs)-related mechanisms, including the direct modulation of mitochondrial dynamics through the PPARγ-coactivator-1α (PGC-1α) axis and the crosstalk with critical aging- and neurodegenerative-related cellular pathways. In the present review, we revise the current knowledge regarding the molecular aspects of Aβ production and clearance and provide a physiological context that gives a more complete view of this issue. Additionally, we consider the different structures involved in AD-altered Aβ brain balance, which could be directly or indirectly affected by a nuclear receptor (NR)/PPAR-related mechanism.

  3. Perchlorate exposure induces hypothyroidism and affects thyroid-responsive genes in liver but not brain of quail chicks.

    PubMed

    Chen, Yu; McNabb, F M Anne; Sible, Jill C

    2009-10-01

    Ground-dwelling birds in perchlorate-contaminated areas are exposed to perchlorate ion, a known thyroid disruptor, and might be vulnerable to the developmental effects of perchlorate-induced hypothyroidism. We hypothesized that perchlorate-induced hypothyroidism would alter the expression of thyroid-responsive genes involved in thyroid hormone (TH) regulation and in the development of target organ function. Japanese quail chicks were exposed to 2000 mg/L ammonium perchlorate in drinking water for 7.5 weeks beginning on day 5 posthatch. Hypothyroidism was evident after 2 weeks of exposure as lower plasma THs and lower TH content in exposed chicks than in controls. The degree of hypothyroidism was increased at 7.5 weeks, as indicated by significant thyroid gland hypertrophy and sustained changes in thyroid function. After 2 weeks of exposure, hypothyroidism increased type 2 5'-deiodinase (D2) mRNA level and decreased Spot 14 (SP14) mRNA level in the liver, whereas D2 mRNA and RC3 mRNA levels in brain were not affected. After 7.5 weeks of exposure, mRNA levels in the exposed group did not differ from those in controls in either the liver or brain, suggesting the responsiveness of these genes to THs decreased during development. These results suggest that the brain, but not the liver, was protected from the effects of hypothyroidism, probably by changes in D2 activity at the protein level and/or regulation of TH entry and exit from the brain. We concluded that perchlorate exposure caused hypothyroidism in young Japanese quail and affected the expression of thyroid-responsive genes during early posthatch development.

  4. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease

    PubMed Central

    Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M.; Hunter, Jill V.; Atik, Mehmed M.; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O.; Bozdogan, Sevcan Tug; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C.; Jain, Preti; Geckinli, B. Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D.; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M.; Adams, David R.; Boerwinkle, Eric; Chung, Wendy K.; Gibbs, Richard A.; Lupski, James R

    2015-01-01

    Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID:26539891

  5. Proline affects brain function in 22q11DS children with the low activity COMT 158 allele.

    PubMed

    Vorstman, Jacob A S; Turetsky, Bruce I; Sijmens-Morcus, Monique E J; de Sain, Monique G; Dorland, Bert; Sprong, Mirjam; Rappaport, Eric F; Beemer, Frits A; Emanuel, Beverly S; Kahn, René S; van Engeland, Herman; Kemner, Chantal

    2009-02-01

    The association between the 22q11.2 deletion syndrome (22q11DS) and psychiatric disorders, particularly psychosis, suggests a causal relationship between 22q11DS genes and abnormal brain function. The genes catechol-O-methyl-transferase (COMT) and proline dehydrogenase both reside within the commonly deleted region of 22q11.2. COMT activity and proline levels may therefore be altered in 22q11DS individuals. Associations of both COMT(158) genotype and elevated serum proline levels with abnormal brain function have been reported. Fifty-six 22q11DS children and 75 healthy controls were assessed on physiological measures of brain function, including prepulse inhibition (PPI) of startle, P50 auditory sensory gating and smooth pursuit eye movements (SPEM). COMT(158) genotype and plasma proline levels were determined in the 22q11DS children. We hypothesized an interaction between the COMT(158) genotype and proline, predicting the strongest negative effect of high proline on brain function to occur in 22q11DS children who are carriers of the COMT(met) allele. Of the three physiological measures, only SPEM and PPI were abnormal in the patient sample. With regard to the SPEM performance, there was a significant interaction between the COMT(158) genotype and proline level with significantly decreased SPEM performance in children with high plasma proline levels and the low activity COMT(met) allele. A similar interaction effect was not observed with regard to PPI. These findings are consistent with a model in which elevated proline negatively affects brain function by an increase in dopamine in the prefrontal cortex. 22q11DS patients with low dopamine catabolic capacity are therefore especially vulnerable to this functional disruption.

  6. COMT genotype affects brain white matter pathways in attention-deficit/hyperactivity disorder.

    PubMed

    Hong, Soon-Beom; Zalesky, Andrew; Park, Subin; Yang, Young-Hui; Park, Min-Hyeon; Kim, BoAh; Song, In-Chan; Sohn, Chul-Ho; Shin, Min-Sup; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Jae-Won

    2015-01-01

    Increased dopamine availability may be associated with impaired structural maturation of brain white matter connectivity. This study aimed to derive a comprehensive, whole-brain characterization of large-scale axonal connectivity differences in attention-deficit/hyperactivity disorder (ADHD) associated with catechol-O-methyltransferase gene (COMT) Val158Met polymorphism. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in youth with ADHD who were COMT Val-homozygous (N = 29) compared with those who were Met-carriers (N = 29). Additionally, we examined whether dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) polymorphisms were associated with white matter differences. Level of attention was assessed using the continuous performance test before and after an 8-week open-label trial of methylphenidate (MPH). A network of white matter connections linking 18 different brain regions was significantly weakened in youth with ADHD who were COMT Met-carriers compared to those who were Val-homozygous (P < 0.05, family-wise error-corrected). A measure of white matter integrity, fractional anisotropy, was correlated with impaired pretreatment performance in continuous performance test omission errors and response time variability, as well as with improvement in continuous performance test response time variability after MPH treatment. Altered white matter connectivity was exclusively based on COMT genotypes, and was not evident in DAT1 or DRD4. We demonstrated that white matter connectivity in youth with ADHD is associated with COMT Val158Met genotypes. The present findings suggest that different layers of dopamine-related genes and interindividual variability in the genetic polymorphisms should be taken into account when investigating the human connectome.

  7. Alcohol affects the brain's resting-state network in social drinkers.

    PubMed

    Lithari, Chrysa; Klados, Manousos A; Pappas, Costas; Albani, Maria; Kapoukranidou, Dorothea; Kovatsi, Leda; Bamidis, Panagiotis D; Papadelis, Christos L

    2012-01-01

    Acute alcohol intake is known to enhance inhibition through facilitation of GABA(A) receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN). To test our hypothesis, electroencephalographic (EEG) measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC) on standardized Low Resolution Electromagnetic Tomography (sLORETA) solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected) in alpha, beta (eyes-open) and theta bands (eyes-closed) following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05). Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo). Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as expected

  8. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

    PubMed Central

    Barth, Claudia; Villringer, Arno; Sacher, Julia

    2015-01-01

    Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo. PMID:25750611

  9. In Utero Exposure to Diethylhexyl Phthalate Affects Rat Brain Development: A Behavioral and Genomic Approach

    PubMed Central

    Lin, Han; Yuan, Kaiming; Li, Linyan; Liu, Shiwen; Li, Senlin; Hu, Guoxin; Lian, Qing-Quan; Ge, Ren-Shan

    2015-01-01

    Diethylhexyl phthalate (DEHP) is one of the most widely utilized phthalate plasticizers. Previous studies have demonstrated that gestational or postnatal DEHP exposure induced adverse effects on rat brain development and function. In this study, we investigated the effects of gestational DEHP exposure on gene expression profiling in neonatal rat brain and cognitive function change at adulthood. Adult Sprague Dawley dams were orally treated with 10 or 750 mg/kg DEHP from gestational day 12 to 21. Some male pups were euthanized at postnatal day 1 for gene expression profiling, and the rest males were retained for water maze testing on postnatal day (PND) 56. DEHP showed dose-dependent impairment of learning and spatial memory from PND 56 to 63. Genome-wide microarray analysis showed that 10 and 750 mg/kg DEHP altered the gene expression in the neonatal rat brain. Ccnd1 and Cdc2, two critical genes for neuron proliferation, were significantly down-regulated by DEHP. Interestingly, 750 mg/kg DEHP significantly increased Pmch level. Our study demonstrated the changed gene expression patterns after in utero DEHP exposure might partially contribute to the deficit of cognitive function at adulthood. PMID:26516888

  10. The rate of training response to aerobic exercise affects brain function of rats.

    PubMed

    Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Mimura, Tatsuya; Pajk, Melitta; Abraham, Dora; Koch, Lauren Gerard; Britton, Steven L; Higuchi, Mitsuru; Boldogh, Istvan; Radak, Zsolt

    2016-10-01

    There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p < 0.05). On the reverse Morris Maze test HRT-trained rats outperformed HRT control ones. Significant difference was noted between LRT and HRT groups in redox milieu as assessed by levels of reactive oxygen species (ROS), carbonylation of proteins, nNOS and S-nitroso-cysteine. Moreover the silent information regulator 1 (SIRT1), brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats.

  11. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging

    PubMed Central

    Sawiak, Stephen J.; Perumal, Sunthara Rajan; Rudiger, Skye R.; Matthews, Loren; Mitchell, Nadia L.; McLaughlan, Clive J.; Bawden, C. Simon; Palmer, David N.; Kuchel, Timothy; Morton, A. Jennifer

    2015-01-01

    Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy. PMID:26161747

  12. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship.

  13. High-resolution three-dimensional quantitative map of the macromolecular proton fraction distribution in the normal rat brain.

    PubMed

    Naumova, Anna V; Akulov, Andrey E; Khodanovich, Marina Yu; Yarnykh, Vasily L

    2017-02-01

    The presented dataset provides a normative high-resolution three-dimensional (3D) macromolecular proton fraction (MPF) map of the healthy rat brain in vivo and source images used for its reconstruction. The images were acquired using the protocol described elsewhere (Naumova, et al. High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields. Neuroimage (2016) doi: 10.1016/j.neuroimage.2016.09.036). The map was reconstructed from three source images with different contrast weightings (proton density, T1, and magnetization transfer) using the single-point algorithm with a synthetic reference image. Source images were acquired from a living animal on an 11.7 T small animal MRI scanner with isotropic spatial resolution of 170 µm(3) and total acquisition time about 1.5 h. The 3D dataset can be used for multiple purposes including interactive viewing of rat brain anatomy, measurements of reference MPF values in various brain structures, and development of image processing techniques for the rodent brain segmentation. It also can serve as a gold standard image for implementation and optimization of rodent brain MRI protocols.

  14. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  15. Regional brain activity and strenuous exercise: predicting affective responses using EEG asymmetry.

    PubMed

    Hall, Eric E; Ekkekakis, Panteleimon; Petruzzello, Steven J

    2007-05-01

    Previous research using the model proposed by Davidson has shown that resting frontal electroencephalographic (EEG) asymmetry can predict affective responses to aerobic exercise at moderate intensities. Specifically, greater relative left frontal activity has been shown to predict positive affect (i.e., energy) following exercise. The purpose of this study was to determine if resting frontal EEG asymmetry would predict affective responses following strenuous exercise. Thirty participants (13 women, 17 men) completed a maximal graded exercise test on a treadmill. EEG was recorded prior to exercise. Affect was measured by the Activation Deactivation Adjective Check List prior to the graded exercise test, immediately following, 10 and 20-min following exercise. Greater relative left frontal activity predicted tiredness and calmness during recovery from exercise, but not tension or energy. Tiredness and calmness following exercise covaried, suggesting that tiredness following exercise might not have been linked with displeasure. These findings offer further support for the link between EEG asymmetry and affective responses to exercise.

  16. Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence.

    PubMed

    Soloff, Paul H; White, Richard; Omari, Amro; Ramaseshan, Karthik; Diwadkar, Vaibhav A

    2015-07-30

    Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and the basal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic

  17. Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence

    PubMed Central

    Soloff, Paul H.; White, Richard; Omari, Amro; Ramaseshan, Karthik; Diwadka, Vaibhav A.

    2015-01-01

    Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and thebasal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic

  18. Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury.

    PubMed

    Kumar, Rajesh; Gupta, Rakesh K; Rao, Sajja B; Chawla, Sanjeev; Husain, Mazhar; Rathore, Ram K S

    2003-10-01

    Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.

  19. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    SciTech Connect

    Zhu, Changlian; Gao, Jianfeng; Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu; Kuhn, Hans-Georg; Blomgren, Klas

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  20. Affective Priming by Simple Geometric Shapes: Evidence from Event-related Brain Potentials

    PubMed Central

    Wang, Yinan; Zhang, Qin

    2016-01-01

    Previous work has demonstrated that simple geometric shapes may convey emotional meaning using various experimental paradigms. However, whether affective meaning of simple geometric shapes can be automatically activated and influence the evaluations of subsequent stimulus is still unclear. Thus the present study employed an affective priming paradigm to investigate whether and how two geometric shapes (circle vs. downward triangle) impact on the affective processing of subsequently presented faces (Experiment 1) and words (Experiment 2). At behavioral level, no significant effect of affective congruency was found. However, ERP results in Experiment 1 and 2 showed a typical effect of affective congruency. The LPP elicited by affectively incongruent trials was larger compared to congruent trials. Our results provide support for the notion that downward triangle is perceived as negative and circle as positive and their emotional meaning can be activated automatically and then exert an influence on the electrophysiological processing of subsequent stimuli. The lack of significant congruent effect in behavioral measures and the inversed N400 congruent effect might reveal that the affective meaning of geometric shapes is weak because they are just abstract threatening cues rather than real threat. In addition, because no male participants are included in the present study, our findings are limited to females. PMID:27379001

  1. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

    PubMed Central

    Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient’s APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient’s APOE status is missing. PMID:27410431

  2. A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy

    NASA Astrophysics Data System (ADS)

    Grova, C.; Jannin, P.; Biraben, A.; Buvat, I.; Benali, H.; Bernard, A. M.; Scarabin, J. M.; Gibaud, B.

    2003-12-01

    Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within

  3. A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy.

    PubMed

    Grova, C; Jannin, P; Biraben, A; Buvat, I; Benali, H; Bernard, A M; Scarabin, J M; Gibaud, B

    2003-12-21

    Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within

  4. Viscoelastic properties of normal and cancerous human breast cells are affected differently by contact to adjacent cells.

    PubMed

    Schierbaum, Nicolas; Rheinlaender, Johannes; Schäffer, Tilman E

    2017-04-07

    Malignant transformation drastically alters the mechanical properties of the cell and its response to the surrounding cellular environment. We studied the influence of the physical contact between adjacent cells in an epithelial monolayer on the viscoelastic behavior of normal MCF10A, non-invasive cancerous MCF7, and invasive cancerous MDA-MB-231 human breast cells. Using an atomic force microscopy (AFM) imaging technique termed force clamp force mapping (FCFM) to record images of the viscoelastic material properties of sparse and confluent cells, we found that normal MCF10A cells are stiffer and have a lower fluidity when at confluent than at sparse density. Contrarily, cancerous MCF7 and MDA-MB-231 cells do not stiffen and do not decrease their fluidity when progressing from sparse to confluent density. The behavior of normal MCF10A cells appears to be governed by the formation of stable cell-cell contacts, because their disruption with a calcium-chelator (EGTA) causes the stiffness and fluidity values to return to those at sparse density. In contrast, EGTA-treatment of MCF7 and MDA-MB-231 cells does not change their viscoelastic properties. Confocal fluorescence microscopy showed that the change of the viscoelastic behavior in MCF10A cells when going from sparse to confluent density is accompanied by a remodeling of the actin cytoskeleton into thick stress fiber bundles, while in MCF7 and MDA-MB-231 cells the actin cytoskeleton is only composed of thin and short fibers, regardless of cell density. While the observed behavior of normal MCF10A cells might be crucial for providing mechanical stability and thus in turn integrity of the epithelial monolayer, the dysregulation of this behavior in cancerous MCF7 and MDA-MB-231 cells is possibly a central aspect of cancer progression in the epithelium.

  5. Temperature rise under normal and caries-affected primary tooth dentin disks during polymerization of adhesives and resin-containing dental materials.

    PubMed

    Tosun, Gul; Usumez, Aslihan; Yondem, Isa; Sener, Yagmur

    2008-05-01

    The purpose of this study was to compare the temperature rise under normal and caries-affected primary tooth dentin during photopolymerization of two adhesives and resin-containing restorative materials. Caries-affected and normal dentin disks were prepared from extracted primary molars with only mesial or distal approximal caries (4 mm in diameter, 1 mm in height). Temperature rise during photopolymerization of adhesive materials was measured with a J-type thermocouple wire that was connected to a data logger. Data were analyzed with two-way ANOVA and independent samples t-test. Temperature rise under caries-affected primary tooth dentin disks was higher than that of normal primary tooth dentin disks during polymerization of both adhesive systems and resin-containing dental materials (p < 0.05). It was found that adhesive systems induced a higher temperature rise during polymerization as compared to the resin-containing restorative materials (p < 0.05). In particular, temperature rise during polymerization of adhesive materials exceeded 5.5 degrees C under caries-affected primary tooth dentin.

  6. Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway

    PubMed Central

    Xiao, Xiaolan

    2017-01-01

    This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH. PMID:28337226

  7. The molecular mechanisms affecting N-acetylaspartate homeostasis following experimental graded traumatic brain injury.

    PubMed

    Di Pietro, Valentina; Amorini, Angela Maria; Tavazzi, Barbara; Vagnozzi, Roberto; Logan, Ann; Lazzarino, Giacomo; Signoretti, Stefano; Lazzarino, Giuseppe; Belli, Antonio

    2014-03-24

    To characterize the molecular mechanisms of N-acetylaspartate (NAA) metabolism following traumatic brain injury (TBI), we measured the NAA, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) concentrations and calculated the ATP/ADP ratio at different times from impact, concomitantly evaluating the gene and protein expressions controlling NAA homeostasis (the NAA synthesizing and degrading enzymes N-acetyltransferase 8-like and aspartoacylase, respectively) in rats receiving either mild or severe TBI. The reversible changes in NAA induced by mild TBI were due to a combination of transient mitochondrial malfunctioning with energy crisis (decrease in ATP and in the ATP/ADP ratio) and modulation in the gene and protein levels of N-acetyltransferase 8-like and increase of aspartoacylase levels. The irreversible decrease in NAA following severe TBI, was instead characterized by profound mitochondrial malfunctioning (constant 65% decrease of the ATP/ADP indicating permanent impairment of the mitochondrial phosphorylating capacity), dramatic repression of the N-acetyltransferase 8-like gene and concomitant remarkable increase in the aspartoacylase gene and protein levels. The mechanisms underlying changes in NAA homeostasis following graded TBI might be of note for possible new therapeutic approaches and will help in understanding the effects of repeat concussions occurring during particular periods of the complex NAA recovery process, coincident with the so called window of brain vulnerability.

  8. Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene?)

    USGS Publications Warehouse

    Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

    1996-01-01

    Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5-2 ppm acephate. The regions exhibited cholinesterase recovery at 2-16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: (1) ChE resistance threshold, (2) ChE compensation threshold, and (3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

  9. Direction of Biological Motion Affects Early Brain Activation: A Link with Social Cognition

    PubMed Central

    Pegna, Alan John; Gehring, Elise; Meyer, Georg; Del Zotto, Marzia

    2015-01-01

    A number of EEG studies have investigated the time course of brain activation for biological movement over this last decade, however the temporal dynamics of processing are still debated. Moreover, the role of direction of movement has not received much attention even though it is an essential component allowing us to determine the intentions of the moving agent, and thus permitting the anticipation of potential social interactions. In this study, we examined event-related responses (ERPs) in 15 healthy human participants to light point walkers and their scrambled counterparts, whose movements occurred either in the radial or in the lateral plane. Compared to scrambled motion (SM), biological motion (BM) showed an enhanced negativity between 210 and 360ms. A source localization algorithm (sLORETA) revealed that this was due to an increase in superior and middle temporal lobe activity. Regarding direction, we found that radial BM produced an enhanced P1 compared to lateral BM, lateral SM and radial SM. This heightened P1 was due to an increase in activity in extrastriate regions, as well as in superior temporal, medial parietal and medial prefrontal areas. This network is known to be involved in decoding the underlying intentionality of the movement and in the attribution of mental states. The social meaning signaled by the direction of biological motion therefore appears to trigger an early response in brain activity. PMID:26121591

  10. How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1

    PubMed Central

    Serra, Laura; Petrucci, Antonio; Spanò, Barbara; Torso, Mario; Olivito, Giusy; Lispi, Ludovico; Costanzi-Porrini, Sandro; Giulietti, Giovanni; Koch, Giacomo; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Summary Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tract-based spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1 mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1. PMID:26214024

  11. Changes in emotional empathy, affective responsivity, and behavior following severe traumatic brain injury.

    PubMed

    de Sousa, Arielle; McDonald, Skye; Rushby, Jacqueline

    2012-01-01

    This study was designed to examine the relationship between deficits in empathy, emotional responsivity, and social behavior in adults with severe traumatic brain injury (TBI). A total of 21 patients with severe TBI and 25 control participants viewed six film clips containing pleasant, unpleasant, and neutral content whilst facial muscle responses, skin conductance, and valence and arousal ratings were measured. Emotional empathy (the Balanced Emotional Empathy Scale, BEES: self-report) and changes in drive and control in social situations (The Current Behaviour Scale, CBS: relative report) were also assessed. In comparison to control participants, those in the TBI group reported less ability to empathize emotionally and had reduced facial responding to both pleasant and unpleasant films. They also exhibited lowered autonomic arousal, as well as abnormal ratings of valence and arousal, particularly to unpleasant films. Relative reported loss of emotional control was significantly associated with heightened empathy, while there was a trend to suggest that impaired drive (or motivation) may be related to lower levels of emotional empathy. The results represent the first to suggest that level of emotional empathy post traumatic brain injury may be associated with behavioral manifestations of disorders of drive and control.

  12. Is it a baby? Perceived age affects brain processing of faces differently in women and men.

    PubMed

    Proverbio, Alice Mado; Riva, Federica; Zani, Alberto; Martin, Eleonora

    2011-11-01

    It is known that infant faces stimulate visual and anterior brain regions belonging to the mesocortical limbic system (orbito-frontal cortex, anterior cingulate cortex, and nucleus accumbens) as well as the fusiform gyrus during face coding, suggesting a preferential response to baby schema. In the present investigation, faces of infants, children, and adults were presented to 40 male and female right-handed university students with technological objects (and inanimate scenarios to serve as targets) in a randomly mixed fashion. EEG was recorded from 128 scalp sites. In both sexes, the N1 response to infant faces was larger than the response to adult faces; however, the baby-specific N1 response was much larger in women than in men across the left hemisphere. The anterior N2 response to infants was greater than the response to children only in women, whereas the response to children of any age was larger than the response to adults in men. LORETA identified the intracranial sources of N2 response to infants in the left fusiform gyrus (FG), as well as the uncus, cingulate, and orbito-frontal cortices. The FG, the limbic, and especially the orbito-frontal sources were much larger in women than in men. The data suggest a sex difference in the brain response to faces of different ages and in the preferential response to infants, especially with regard to activation of the mesocorticolimbic system.

  13. "Where Brains Had a Chance": William Mayo and Rhetorical Instruction at East Texas Normal College, 1889-1917

    ERIC Educational Resources Information Center

    Gold, David

    2005-01-01

    The rhetorical training of students at East Texas Normal College is examined with reference to the rhetorical practices and educational ideologies of William Mayo, the experiences of his students and the features of his teaching. Examination of the history of schools like East Texas Normal College helps in dealing with concerns regarding…

  14. An In Vivo Microdialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson's Disease Model Rats

    PubMed Central

    Hou, Jinfeng; Liu, Qian; Li, Yingfei; Sun, Hua; Zhang, Jinlan

    2014-01-01

    FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson's disease (PD) agent. The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats. In vivo microdialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl). A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates. No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats. However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models. In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats. These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain. These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances. PMID:25045708

  15. An in vivo microdialysis study of FLZ penetration through the blood-brain barrier in normal and 6-hydroxydopamine induced Parkinson's disease model rats.

    PubMed

    Hou, Jinfeng; Liu, Qian; Li, Yingfei; Sun, Hua; Zhang, Jinlan

    2014-01-01

    FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson's disease (PD) agent. The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats. In vivo microdialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl). A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates. No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats. However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models. In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats. These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain. These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances.

  16. Does IQ affect the functional brain network involved in pseudoword reading in students with reading disability? A magnetoencephalography study.

    PubMed

    Simos, Panagiotis G; Rezaie, Roozbeh; Papanicolaou, Andrew C; Fletcher, Jack M

    2014-01-01

    The study examined whether individual differences in performance and verbal IQ affect the profiles of reading-related regional brain activation in 127 students experiencing reading difficulties and typical readers. Using magnetoencephalography in a pseudoword read-aloud task, we compared brain activation profiles of students experiencing word-level reading difficulties who did (n = 29) or did not (n = 36) meet the IQ-reading achievement discrepancy criterion. Typical readers assigned to a lower-IQ (n = 18) or a higher IQ (n = 44) subgroup served as controls. Minimum norm estimates of regional cortical activity revealed that the degree of hypoactivation in the left superior temporal and supramarginal gyri in both RD subgroups was not affected by IQ. Moreover, IQ did not moderate the positive association between degree of activation in the left fusiform gyrus and phonological decoding ability. We did find, however, that the hypoactivation of the left pars opercularis in RD was restricted to lower-IQ participants. In accordance with previous morphometric and fMRI studies, degree of activity in inferior frontal, and inferior parietal regions correlated with IQ across reading ability subgroups. Results are consistent with current views questioning the relevance of IQ-discrepancy criteria in the diagnosis of dyslexia.

  17. Suppression of the endoplasmic reticulum calcium pump during zebrafish gastrulation affects left-right asymmetry of the heart and brain.

    PubMed

    Kreiling, Jill A; Balantac, Zaneta L; Crawford, Andrew R; Ren, Yuexin; Toure, Jamal; Zchut, Sigalit; Kochilas, Lazaros; Creton, Robbert

    2008-01-01

    Vertebrate embryos generate striking Ca(2+) patterns, which are unique regulators of dynamic developmental events. In the present study, we used zebrafish embryos as a model system to examine the developmental roles of Ca(2+) during gastrulation. We found that gastrula stage embryos maintain a distinct pattern of cytosolic Ca(2+) along the dorsal-ventral axis, with higher Ca(2+) concentrations in the ventral margin and lower Ca(2+) concentrations in the dorsal margin and dorsal forerunner cells. Suppression of the endoplasmic reticulum Ca(2+) pump with 0.5 microM thapsigargin elevates cytosolic Ca(2+) in all embryonic regions and induces a randomization of laterality in the heart and brain. Affected hearts, visualized in living embryos by a subtractive imaging technique, displayed either a reversal or loss of left-right asymmetry. Brain defects include a left-right reversal of pitx2 expression in the dorsal diencephalon and a left-right reversal of the prominent habenular nucleus in the brain. Embryos are sensitive to inhibition of the endoplasmic reticulum Ca(2+) pump during early and mid gastrulation and lose their sensitivity during late gastrulation and early segmentation. Suppression of the endoplasmic reticulum Ca(2+) pump during gastrulation inhibits expression of no tail (ntl) and left-right dynein related (lrdr) in the dorsal forerunner cells and affects development of Kupffer's vesicle, a ciliated organ that generates a counter-clockwise flow of fluid. Previous studies have shown that Ca(2+) plays a role in Kupffer's vesicle function, influencing ciliary motility and translating the vesicle's counter-clockwise flow into asymmetric patterns of gene expression. The present results suggest that Ca(2+) plays an additional role in the formation of Kupffer's vesicle.

  18. Affective Pacman: A Frustrating Game for Brain-Computer Interface Experiments

    NASA Astrophysics Data System (ADS)

    Reuderink, Boris; Nijholt, Anton; Poel, Mannes

    We present the design and development of Affective Pacman, a game that induces frustration to study the effect of user state changes on the EEG signal. Affective Pacman is designed to induce frustration for short periods, and allows the synchronous recording of a wide range of sensors, such as physiological sensors and EEG in addition to the game state. A self-assessment is integrated in the game to track changes in user state. Preliminary results indicate a significant effect of the frustration induction on the EEG.

  19. Decision making in the ageing brain: changes in affective and motivational circuits.

    PubMed

    Samanez-Larkin, Gregory R; Knutson, Brian

    2015-05-01

    As the global population ages, older decision makers will be required to take greater responsibility for their own physical, psychological and financial well-being. With this in mind, researchers have begun to examine the effects of ageing on decision making and associated neural circuits. A new 'affect-integration-motivation' (AIM) framework may help to clarify how affective and motivational circuits support decision making. Recent research has shed light on whether and how ageing influences these circuits, providing an interdisciplinary account of how ageing can alter decision making.

  20. 7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma

    SciTech Connect

    Lupo, Janine M.; Chuang, Cynthia F.; Chang, Susan M.; Barani, Igor J.; Jimenez, Bert; Hess, Christopher P.; Nelson, Sarah J.

    2012-03-01

    Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

  1. Monoterpenoid-based preparations in beehives affect learning, memory, and gene expression in the bee brain.

    PubMed

    Bonnafé, Elsa; Alayrangues, Julie; Hotier, Lucie; Massou, Isabelle; Renom, Allan; Souesme, Guillaume; Marty, Pierre; Allaoua, Marion; Treilhou, Michel; Armengaud, Catherine

    2017-02-01

    Bees are exposed in their environment to contaminants that can weaken the colony and contribute to bee declines. Monoterpenoid-based preparations can be introduced into hives to control the parasitic mite Varroa destructor. The long-term effects of monoterpenoids are poorly investigated. Olfactory conditioning of the proboscis extension reflex (PER) has been used to evaluate the impact of stressors on cognitive functions of the honeybee such as learning and memory. The authors tested the PER to odorants on bees after exposure to monoterpenoids in hives. Octopamine receptors, transient receptor potential-like (TRPL), and γ-aminobutyric acid channels are thought to play a critical role in the memory of food experience. Gene expression levels of Amoa1, Rdl, and trpl were evaluated in parallel in the bee brain because these genes code for the cellular targets of monoterpenoids and some pesticides and neural circuits of memory require their expression. The miticide impaired the PER to odors in the 3 wk following treatment. Short-term and long-term olfactory memories were improved months after introduction of the monoterpenoids into the beehives. Chronic exposure to the miticide had significant effects on Amoa1, Rdl, and trpl gene expressions and modified seasonal changes in the expression of these genes in the brain. The decrease of expression of these genes in winter could partly explain the improvement of memory. The present study has led to new insights into alternative treatments, especially on their effects on memory and expression of selected genes involved in this cognitive function. Environ Toxicol Chem 2017;36:337-345. © 2016 SETAC.

  2. Diffuse traumatic brain injury affects chronic corticosterone function in the rat

    PubMed Central

    Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan

    2016-01-01

    As many as 20–55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result fr