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Sample records for affect normal brain

  1. Telomerase deficiency affects normal brain functions in mice.

    PubMed

    Lee, Jaehoon; Jo, Yong Sang; Sung, Young Hoon; Hwang, In Koo; Kim, Hyuk; Kim, Song-Yi; Yi, Sun Shin; Choi, June-Seek; Sun, Woong; Seong, Je Kyung; Lee, Han-Woong

    2010-02-01

    Telomerase maintains telomere structures and chromosome stability, and it is essential for preserving the characteristics of stem and progenitor cells. In the brain, the hippocampus and the olfactory bulbs are continuously supplied with neural stem and progenitor cells that are required for adult neurogenesis throughout the life. Therefore, we examined whether telomerase plays important roles in maintaining normal brain functions in vivo. Telomerase reverse transcriptase (TERT) expression was observed in the hippocampus, the olfactory bulbs, and the cerebellum, but the telomerase RNA component (TERC) was not detected in hippocampus and olfactory bulbs. Interestingly, TERT-deficient mice exhibited significantly altered anxiety-like behaviors and abnormal olfaction measuring the functions of the hippocampus and the olfactory bulbs, respectively. However, the cerebellum-dependent behavior was not changed in these mutant mice. These results suggest that TERT is constitutively expressed in the hippocampus and the olfactory bulbs, and that it is important for regulating normal brain functions. PMID:19685288

  2. Treatment parameters affecting the response of normal brain to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Chen, Qun; Chopp, Michael; Dereski, Mary O.; Wilson, Brian C.; Patterson, Michael S.; Kessel, David; Heads, Larry; Hetzel, Fred W.

    1993-06-01

    Different aspects of photodynamic therapy in normal rat brain tissue have been studied, in an effort to understand and improve the dosimetry of this new modality in treatment of brain tumors. dosimetry parameters, including light energy dose, fluence rate and beam size, and drug dosage were studied. PDT induced lesion depth in brain was measured as a biological endpoint. Effective attenuation depth and absolute light fluence rate distribution under superficial irradiation were measured using invasive optical probes. Photosensitizer uptake was quantified using HPLC analysis. The results indicate that normal brain have a high intrinsic sensitivity to PDT treatment, based on the estimated photodynamic threshold.

  3. Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD

    PubMed Central

    Murray, John; Tsui, Wai H.; Spector, Nicole; Goldowsky, Alexander; Williams, Schantel; Osorio, Ricardo; McHugh, Pauline; Glodzik, Lidia; Vallabhajosula, Shankar; de Leon, Mony J.

    2014-01-01

    Objectives: This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD. Methods: Fifty-two NL individuals received MRI, 11C-Pittsburgh compound B (PiB)-PET, and 18F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n = 13/group, aged 32–72 years, 60% female, 30% APOE ε4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH−). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volume–corrected PiB retention, and FDG metabolism across FH groups and vs FH−. Results: NL FHmp showed more severe abnormalities in all 3 biomarkers vs the other groups regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in FHmp, intermediate in FHm, and lowest in FHp and FH−. GMV reductions were highest in FHmp and intermediate in FHm and FHp vs FH−. In all FH+ groups, amyloid-β deposition exceeded GMV loss and hypometabolism exceeded GMV loss (p < 0.001), while amyloid-β deposition exceeded hypometabolism in FHmp and FHp but not in FHm. Conclusions: These biomarker findings show a “LOAD parent-dose effect” in NL individuals several years, if not decades, before possible clinical symptoms. PMID:24523481

  4. Brain spatial normalization.

    PubMed

    Bug, William; Gustafson, Carl; Shahar, Allon; Gefen, Smadar; Fan, Yingli; Bertrand, Louise; Nissanov, Jonathan

    2007-01-01

    Neuroanatomical informatics, a subspecialty of neuroinformatics, focuses on technological solutions to neuroimage database access. Its current main goal is an image-based query system that is able to retrieve imagery based on anatomical location. Here, we describe a set of tools that collectively form such a solution for sectional material and that are available to investigators to use on their own data sets. The system accepts slide images as input and yields a matrix of transformation parameters that map each point on the input image to a standardized 3D brain atlas. In essence, this spatial normalization makes the atlas a spatial indexer from which queries can be issued simply by specifying a location on the reference atlas. Our objective here is to familiarize potential users of the system with the steps required of them as well as steps that take place behind the scene. We detail the capabilities and the limitations of the current implementation and briefly describe the enhancements planned for the near future.

  5. How Body Affects Brain.

    PubMed

    Suzuki, Wendy A

    2016-08-01

    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. PMID:27508865

  6. Spatial normalization of brain images and beyond.

    PubMed

    Mangin, J-F; Lebenberg, J; Lefranc, S; Labra, N; Auzias, G; Labit, M; Guevara, M; Mohlberg, H; Roca, P; Guevara, P; Dubois, J; Leroy, F; Dehaene-Lambertz, G; Cachia, A; Dickscheid, T; Coulon, O; Poupon, C; Rivière, D; Amunts, K; Sun, Z Y

    2016-10-01

    The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images.

  7. Spatial normalization of brain images and beyond.

    PubMed

    Mangin, J-F; Lebenberg, J; Lefranc, S; Labra, N; Auzias, G; Labit, M; Guevara, M; Mohlberg, H; Roca, P; Guevara, P; Dubois, J; Leroy, F; Dehaene-Lambertz, G; Cachia, A; Dickscheid, T; Coulon, O; Poupon, C; Rivière, D; Amunts, K; Sun, Z Y

    2016-10-01

    The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images. PMID:27344104

  8. 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. PMID:25185649

  9. 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.

  10. 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%.

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

    MedlinePlus

    ... 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.

  12. Intelligence and Regional Brain Volumes in Normal Controls.

    ERIC Educational Resources Information Center

    Flashman, Laura A.; Andreasen, Nancy C.; Flaum, Michael; Swayze, Victor W., II

    1998-01-01

    The relationship between brain size and intelligence was examined in 90 normal volunteers. Results support the notion of a modest relationship between brain size and measures of global intelligence and suggest diffuse brain involvement on performance tasks that require integration and use of multiple cognitive domains. (Author/SLD)

  13. The ageing brain: normal and abnormal memory.

    PubMed Central

    Albert, M S

    1997-01-01

    With advancing age, the majority of individuals experience declines in their ability to learn and remember. An examination of brain structure and function in healthy older persons across the age range indicates that there are substantial changes in the brain that appear to be related to alterations in memory. The nature of the cognitive and neurobiological alterations associated with age-related change is substantially different from that seen in the early stages of a dementing illness, such as Alzheimer's disease. These differences have implications for potential intervention strategies. PMID:9415922

  14. 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.

  15. Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

    PubMed

    Roy, Michael J; Costanzo, Michelle E; Blair, James R; Rizzo, Albert A

    2014-01-01

    Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD. PMID:24875691

  16. 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

  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. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Determinants of iron accumulation in the normal aging brain.

    PubMed

    Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2016-07-01

    In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. PMID:27255824

  4. Brain regions and genes affecting postural control.

    PubMed

    Lalonde, R; Strazielle, C

    2007-01-01

    Postural control is integrated in all facets of motor commands. The role of cortico-subcortical pathways underlying postural control, including cerebellum and its afferents (climbing, mossy, and noradrenergic fibers), basal ganglia, motor thalamus, and parieto-frontal neocortex has been identified in animal models, notably through the brain lesion technique in rats and in mice with spontaneous and induced mutations. These studies are complemented by analyses of the factors underlying postural deficiencies in patients with cerebellar atrophy. With the gene deletion technique in mice, specific genes expressed in cerebellum encoding glutamate receptors (Grid2 and Grm1) and other molecules (Prkcc, Cntn6, Klf9, Syt4, and En2) have also been shown to affect postural control. In addition, transgenic mouse models of the synucleinopathies and of Huntington's disease cause deficiencies of motor coordination resembling those of patients with basal ganglia damage.

  5. Positive and negative affect recognition in schizophrenia: a comparison with substance abuse and normal control subjects.

    PubMed

    Bell, M; Bryson, G; Lysaker, P

    1997-11-14

    This study had three aims: to compare a schizophrenia sample (n = 50) with a substance abuse (n = 25) and normal sample (n = 81) on affect recognition; to compare differences in their performance between positive and negative affect recognition; and to introduce a new videotape method of stimulus presentation. Subjects were asked to identify the predominant affect depicted in 21 5-10-s vignettes containing three trials of seven affect states. Results demonstrate significant group differences: normal subjects scored in the normal or mild range, substance abuse (s/a) subjects scored in the mild and moderate ranges, and the schizophrenia sample scored predominantly in the moderate to severe ranges. Accuracies were 92.3% for the normal sample, 77.2 for the s/a sample and 64.8 for the schizophrenia sample. Response dispersions were 97.6% for the schizophrenia group, 69% for the s/a sample and 38% in the normal sample. A repeated measures ANOVA revealed a group by type of affect interaction with schizophrenia subjects showing far greater differential impairment on negative affect recognition. Difficulty of item did not contribute to this difference. Test-retest reliability at 5 months for this new method was r = 0.76, and stability of categorization was very high over 5 months (weighted kappa = 0.93). These affect recognition deficits in schizophrenia are discussed as they relate to lateralization of brain function, high EE families, social skills impairment and implications for rehabilitation services. PMID:9463840

  6. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    PubMed

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  7. 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.

  8. Tau protein in normal and Alzheimer's disease brain: an update.

    PubMed

    Johnson, G V; Hartigan, J A

    1999-11-01

    Tau is a microtubule-associated protein that, in a hyperphosphorylated form, comprises the main component of the paired helical filaments and neurofibrillary tangles found in Alzheimer's Disease (AD) brain. It is therefore important to understand the normal functioning and processing of tau protein, and the abnormal posttranslational processing of tau in AD pathology. In 1996, Johnson and Jenkins reviewed the literature on the biochemistry, function, and phosphorylation of tau in normal and AD brain. Since that time, numerous publications have come out further elucidating the properties of tau. The present review updates the topics originally covered in the 1996 review, as well as presents a number of new topics. For example, mutations in the tau gene have been found in several non-AD, autosomal dominant neurodegenerative disorders that exhibit extensive neurofibrillary pathology. In addition, there is increasing evidence that tau may be involved in signal transduction, organelle transport, and cell growth, independent of its microtubule-binding functions. Taken together, the research reviewed here demonstrates that tau is a very complex protein with various functions that are intricately regulated. It is clear that more research is required to completely understand the functions and regulation of tau in normal and AD brain.

  9. Regional distributions of brain glutamate and glutamine in normal subjects.

    PubMed

    Goryawala, Mohammed Z; Sheriff, Sulaiman; Maudsley, Andrew A

    2016-08-01

    Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS-observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short-TE whole-brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high-SNR spectra from atlas-registered anatomic regions or interest. By spectral fitting of high-SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray-matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white-matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white-matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray-matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27351339

  10. Cell migration in the normal and pathological postnatal mammalian brain

    PubMed Central

    Canoll, Peter; Goldman, James E.

    2009-01-01

    In the developing brain, cell migration is a crucial process for structural organization, and is therefore highly regulated to allow the correct formation of complex networks, wiring neurons, and glia. In the early postnatal brain, late developmental processes such as the production and migration of astrocyte and oligodendrocyte progenitors still occur. Although the brain is completely formed and structured few weeks after birth, it maintains a degree of plasticity throughout life, including axonal remodeling, synaptogenesis, but also neural cell birth, migration and integration. The subventricular zone (SVZ) and the dentate gyrus of the hippocampus (DG) are the two main neurogenic niches in the adult brain. Neural stem cells reside in these structures and produce progenitors that migrate toward their ultimate location: the olfactory bulb and granular cell layer of the DG respectively. The aim of this review is to synthesize the increasing information concerning the organization, regulation and function of cell migration in a mature brain. In a normal brain, protein involved in cell-cell or cell-matrix interactions together with secreted proteins acting as chemoattractant or chemorepellant play key roles in the regulation of neural progenitor cell migration. In addition, recent data suggest that gliomas arise from the transformation of neural stem cells or progenitor cells and that glioma cell infiltration recapitulates key aspects of glial progenitor migration. Thus, we will consider glioma migration in the context of progenitor migration. Finally, many observations show that brain lesions and neurological diseases trigger neural stem/progenitor cell activation and migration towards altered structures. The factors involved in such cell migration/recruitment are just beginning to be understood. Inflammation which has long been considered as thoroughly disastrous for brain repair is now known to produce some positive effects on stem/progenitor cell recruitment via

  11. 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.

  12. 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...

  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. Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function.

    PubMed

    Antoniades, Chrystalina A; FitzGerald, James J

    2016-01-01

    The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology. PMID:27501123

  15. 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.

  16. 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

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

    PubMed

    Marín-Padilla, Miguel

    2013-09-01

    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.

  18. Low brain histamine content affects ethanol-induced motor impairment.

    PubMed

    Lintunen, Minnamaija; Raatesalmi, Kristiina; Sallmen, Tina; Anichtchik, Oleg; Karlstedt, Kaj; Kaslin, Jan; Kiianmaa, Kalervo; Korpi, Esa R; Panula, Pertti

    2002-02-01

    The effect of ethanol on motor performance in humans is well established but how neural mechanisms are affected by ethanol action remains largely unknown. To investigate whether the brain histaminergic system is important in it, we used a genetic model consisting of rat lines selectively outbred for differential ethanol sensitivity. Ethanol-sensitive rats had lower levels of brain histamine and lower densities of histamine-immunoreactive fibers than ethanol-insensitive rats, although both rat lines showed no changes in histamine synthesizing neurons. Lowering the high brain histamine content of the ethanol-insensitive rats with alpha-fluoromethylhistidine before ethanol administration increased their ethanol sensitivity in a behavioral motor function test. Higher H3 receptor ligand binding and histamine-induced G-protein activation was detected in several brain regions of ethanol-naive ethanol-sensitive rats. Brain histamine levels and possibly signaling via H3 receptors may thus correlate with genetic differences in ethanol-induced motor impairment.

  19. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    PubMed

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  20. Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brain.

    PubMed

    Malecki, E A; Cook, B M; Devenyi, A G; Beard, J L; Connor, J R

    1999-11-30

    Hypotransferrinemia (hpx/hpx) is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. These mice provide a unique opportunity to examine the role of Tf in Fe and Mn transport in the brain. Twenty weanling wild-type BALB/cJ mice, 15 +/hpx mice, and 12 hpx/hpx mice of both sexes were injected i.v. with either 54MnCl(2) or 59FeCl(3) either 1 h or 1 week before killing at 12 weeks of age. Total brain counts of 54Mn and 59Fe were measured, and regional brain distributions were assessed by autoradiography. Hypotransferrinemia did not affect total brain Mn uptake. However, 1 week after i.v. injection, hpx/hpx mice had less 54Mn in forebrain structures including cerebral cortex, corpus callosum, striatum, and substantia nigra. The +/hpx mice had the highest total brain 59Fe accumulation 1 h after i.v. injection. A striking effect of regional distribution of 59Fe was noted 1 week after injection; in hpx/hpx mice, 59Fe was located primarily in choroid plexus, whereas in +/+ and +/hpx mice 59Fe was widely distributed, with relatively high amounts in cerebral cortex and cerebellum. We interpret these data to mean that Tf is necessary for the transport of Fe but not Mn across the blood-brain barrier, and that there is a Tf-independent uptake mechanism for iron in the choroid plexus. Additionally, these data suggest that endogenous synthesis of Tf is necessary for Fe transport from the choroid plexus. PMID:10561526

  1. Mental training affects distribution of limited brain resources.

    PubMed

    Slagter, Heleen A; Lutz, Antoine; Greischar, Lawrence L; Francis, Andrew D; Nieuwenhuis, Sander; Davis, James M; Davidson, Richard J

    2007-06-01

    The information processing capacity of the human mind is limited, as is evidenced by the so-called "attentional-blink" deficit: When two targets (T1 and T2) embedded in a rapid stream of events are presented in close temporal proximity, the second target is often not seen. This deficit is believed to result from competition between the two targets for limited attentional resources. Here we show, using performance in an attentional-blink task and scalp-recorded brain potentials, that meditation, or mental training, affects the distribution of limited brain resources. Three months of intensive mental training resulted in a smaller attentional blink and reduced brain-resource allocation to the first target, as reflected by a smaller T1-elicited P3b, a brain-potential index of resource allocation. Furthermore, those individuals that showed the largest decrease in brain-resource allocation to T1 generally showed the greatest reduction in attentional-blink size. These observations provide novel support for the view that the ability to accurately identify T2 depends upon the efficient deployment of resources to T1. The results also demonstrate that mental training can result in increased control over the distribution of limited brain resources. Our study supports the idea that plasticity in brain and mental function exists throughout life and illustrates the usefulness of systematic mental training in the study of the human mind.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

    Quarles, C. A.; Ballmann, Charles; Yang, S. H.

    2009-04-01

    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. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. While early results suggested a small decrease in 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. 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.

  4. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26626489

  6. Normal and affectively ill mothers' beliefs about their children.

    PubMed

    Kochanska, G; Radke-Yarrow, M; Kuczynski, L; Friedman, S L

    1987-07-01

    Normal, unipolar, and bipolar depressed women were studied to determine whether depressive cognitive schemas extend to the perception of one's own child. Depressed and well mothers reported equal satisfaction with their children, but the depressed group was less satisfied with the children's socioaffective than their cognitive development. The depressed mothers experienced a greater degree of helplessness regarding their children, and were more likely to feel that outcomes of child development were determined by uncontrollable factors.

  7. 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

  8. Episodic disorders of behaviour and affect after acquired brain injury.

    PubMed

    Eames, Peter Eames; Wood, Rodger Ll

    2003-01-01

    Psychological disorders that follow traumatic brain injury are possibly more complex and diverse than those associated with other forms of "brain damage". These may include organic aggressive, or organic affective syndromes that are episodic in nature and therefore require a more specific diagnosis, a different classification, and a different approach to treatment. Consequently, it is necessary for clinicians to learn to distinguish between "primary" psychiatric illnesses and those disorders of behavioural control and mood that stem specifically from brain injury. There is relatively little in the clinical literature that explains the relationship between variable states of behaviour, mood or temperament, and clinical disorders that may have long-term implications for patient management. This concept paper therefore addresses abnormalities of mood and behaviour that are episodic in character and are not recognisably included in the DSM and ICD classifications of psychological or psychiatric disorders. PMID:21854336

  9. 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.

  10. Contrast medium accumulation and washout in canine brain tumors and irradiated normal brain: a CT study of kinetics

    SciTech Connect

    Fike, J.R.; Cann, C.E.

    1984-04-01

    Kinetics of an iodinated contrast medium were evaluated quantitatively as a function of time up to one hour after intravenous infusion in the brains of dogs with experimentally induced radiation damage and dogs with spontaneous brain tumor. Radiation damage was characterized by an increase in iodine accumulation soon after the infusion, while tumor concentration of iodine either showed no change or decreased with time. These results suggest that contrast kinetic studies may be useful in differentiating radiation damage to normal brain tissue from a malignant brain tumor.

  11. Development of brain mechanisms for processing affective touch

    PubMed Central

    Björnsdotter, Malin; Gordon, Ilanit; Pelphrey, Kevin A.; Olausson, Håkan; Kaiser, Martha D.

    2014-01-01

    Affective tactile stimulation plays a key role in the maturation of neural circuits, but the development of brain mechanisms processing touch is poorly understood. We therefore used functional magnetic resonance imaging (fMRI) to study brain responses to soft brush stroking of both glabrous (palm) and hairy (forearm) skin in healthy children (5–13 years), adolescents (14–17 years), and adults (25–35 years). Adult-defined regions-of-interests in the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), insular cortex and right posterior superior temporal sulcus (pSTS) were significantly and similarly activated in all age groups. Whole-brain analyses revealed that responses in the ipsilateral SII were positively correlated with age in both genders, and that responses in bilateral regions near the pSTS correlated significantly and strongly with age in females but not in males. These results suggest that brain mechanisms associated with both sensory-discriminative and affective-motivational aspects of touch are largely established in school-aged children, and that there is a general continuing maturation of SII and a female-specific increase in pSTS sensitivity with age. Our work establishes a groundwork for future comparative studies of tactile processing in developmental disorders characterized by disrupted social perception such as autism. PMID:24550800

  12. Novel DTI Methodology to Detect and Quantify Injured Regions and Affected Brain Pathways in Traumatic Brain Injury

    PubMed Central

    Singh, Manbir; Jeong, Jeongwon; Hwang, Darryl; Sungkarat, Witaya; Gruen, Peter

    2009-01-01

    Purpose To develop and apply DTI based normalization methodology for the detection and quantification of traumatic brain injury (TBI) and the impact of injury along specific brain pathways in: a) individual TBI subjects, and b) a TBI group. Materials and Methods Normalized DTI tractography was conducted in the native space of 12 TBI and 10 age-matched control subjects using the same number of seeds in each subject, distributed at anatomically equivalent locations. Whole-brain tracts from the control group were mapped onto the head of each TBI subject. Differences in the Fractional Anisotropy (FA) maps between each TBI subject and the control group were computed in a common space using a t-test, transformed back to the individual TBI subject's head-space, and thresholded to form Regions of Interest (ROIs) that were used to sort tracts from the control group and the individual TBI subject. Tract-counts for a given ROI in each TBI subject were compared to group mean for the same ROI to quantify impact of injury along affected pathways. Same procedure was used to compare TBI group to control group in a common space. Results Sites of injury within individual TBI subjects and affected pathways included hippocampal/fornix, inferior fronto-occipital, inferior longitudinal fasciculus, corpus callosum (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study. Conclusions The DTI normalization methodology presented here enables automatic delineation of ROIs within the heads of individual subjects (or in a group). These ROIs not only localize and quantify the extent of injury, but also quantify the impact of injury on affected pathways in an individual or a group of TBI subjects. PMID:19608369

  13. 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.

  14. 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.

  15. 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

  16. 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. PMID:27462216

  17. Clinicopathological Outcomes of Prospectively Followed Normal Elderly Brain Bank Volunteers

    PubMed Central

    Dugger, Brittany N.; Hentz, Joseph G.; Adler, Charles H.; Sabbagh, Marwan N.; Shill, Holly A.; Jacobson, Sandra; Caviness, John N.; Belden, Christine; Driver-Dunckley, Erika; Davis, Kathryn J.; Sue, Lucia I.; Beach, Thomas G.

    2014-01-01

    Existing reports on the frequencies of neurodegenerative diseases are typically based on clinical diagnoses. We sought to determine these frequencies in a prospectively-assessed, community-based autopsy series. Included subjects had normal cognitive and movement disorder assessments at study entry. Of the 119 cases meeting these criteria, 52% were female, median age of study entry was 83.5 years (range 67 to 99), and median duration from first visit until death was 4.3 years (range 0-10). At autopsy a clinico-neuropathological diagnosis was made in 30 cases (25%). Clinicopathological diagnoses included 20 (17%) with Alzheimer's disease (AD), 7 (6%) with vascular dementia, 4 (3%) with progressive supranuclear palsy, (1; 0.8%) with dementia with Lewy bodies, (1; 0.8%) with corticobasal degeneration and (1; 0.8%) with multiple system atrophy. Of those 87 subjects (73%) still clinically normal at death, 33 (38%) had extensive AD pathology (pre-clinical AD), 17 (20%) had incidental Lewy bodies and 4 (5%) had incidental pathology consistent with progressive supranuclear palsy. Diagnoses are not mutually exclusive. Although limited by a relatively small sample size, the neuropathological outcome of these initially normal elderly subjects represents a rough estimate of the incidence of these neurodegenerative conditions over a defined time period. PMID:24487796

  18. Clinicopathological outcomes of prospectively followed normal elderly brain bank volunteers.

    PubMed

    Dugger, Brittany N; Hentz, Joseph G; Adler, Charles H; Sabbagh, Marwan N; Shill, Holly A; Jacobson, Sandra; Caviness, John N; Belden, Christine; Driver-Dunckley, Erika; Davis, Kathryn J; Sue, Lucia I; Beach, Thomas G

    2014-03-01

    Existing reports on the frequencies of neurodegenerative diseases are typically based on clinical diagnoses. We sought to determine these frequencies in a prospectively assessed, community-based autopsy series. Included subjects had normal cognitive and movement disorder assessments at study entry. Of the 119 cases meeting these criteria, 52% were women; the median age of study entry was 83.5 years (range, 67-99 years), and the median duration from the first visit until death was 4.3 years (range, 0-10 years). At autopsy, clinicopathological diagnoses were made in 30 cases (25%). These diagnoses included 20 with Alzheimer disease (AD) (17%), 7 with vascular dementia (6%), 4 with progressive supranuclear palsy (3%), 3 with Parkinson disease and 1 each with dementia with Lewy bodies, corticobasal degeneration, or multiple system atrophy (0.8% each). Of the 87 subjects still clinically normal at death (73%), 33 had extensive AD pathology (preclinical AD) (38%), 17 had incidental Lewy bodies (20%), and 4 had incidental pathology consistent with progressive supranuclear palsy (5%). The diagnoses were not mutually exclusive. Although limited by a relatively small sample size, the neuropathological outcome of these initially normal elderly subjects represents a rough estimate of the incidence of these neurodegenerative conditions over a defined time period. PMID:24487796

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Heat loss and blood flow during hyperthermia in normal canine brain. I: Empirical study and analysis.

    PubMed

    Lyons, B E; Samulski, T V; Cox, R S; Fessenden, P

    1989-01-01

    The effects of blood flow and thermal conduction during microwave hyperthermia were investigated in normal canine brain. Heating was accomplished with an external microstrip spiral antenna and temperature measurements were made using a multichannel fluoroptic thermometry system. In order to determine cooling rates, temperature measurements made during cooling were fitted with a model consisting of a constant value and an exponential term. Data from experiments in both perfused and non-perfused brains could be fitted with this simple model. The resulting cooling rates indicated that heat loss by conduction is comparable to that by blood flow. In another series of experiments, temperature measurements were made during several 1 min cooling intervals in which the power was shut off intermittently during a 35 min heating episode. Results were consistent with a 2-3-fold increase in blood flow rate which occurred gradually throughout the course of heating. Parameters that affect the determination of cooling rates are discussed in terms of the bioheat transfer equation. These investigations demonstrate that a simple heat sink model provides a good representation of the cooling data for the thermal distributions obtained. PMID:2926187

  4. 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...

  5. 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

  6. 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.

  7. 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. PMID:20336685

  8. Relationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity.

    PubMed

    Chételat, Gaël; Landeau, Brigitte; Salmon, Eric; Yakushev, Igor; Bahri, Mohamed Ali; Mézenge, Florence; Perrotin, Audrey; Bastin, Christine; Manrique, Alain; Scheurich, Armin; Scheckenberger, Mathias; Desgranges, Béatrice; Eustache, Francis; Fellgiebel, Andreas

    2013-08-01

    Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes. PMID:23518010

  9. 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.

  10. 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

  11. 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

  12. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    SciTech Connect

    Han, Eun Young; Zhang Xin; Yan Yulong; Sharma, Sunil; Penagaricano, Jose; Moros, Eduardo; Corry, Peter

    2012-01-01

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  13. Biondi ring tangles in the choroid plexus of Alzheimer's disease and normal aging brains: a quantitative study.

    PubMed

    Wen, G Y; Wisniewski, H M; Kascsak, R J

    1999-06-19

    The choroid plexus (CP) performs the vital function of producing up to 90% (450-1000 ml/day) of cerebrospinal fluid (CSF) to nourish and to protect the brain in the CSF suspension. The CP also acts as a selective barrier between blood and CSF to regulate ions and other essential molecules. However, the accumulation of intracellular inclusions called Biondi ring tangles (BRTs) in CP cells of Alzheimer's disease (AD)/aging brains may affect these vital functions of the CP. Statistical analysis of quantitative data on the numbers of CP cells containing BRTs from 54 brains (29 AD and 25 normal control), age range 1-100 years, indicated a significant difference (p<0.00004) between AD and control brains, using analysis of covariance (ANCOVA) with age as covariate. This study compiled the first set of archives to reveal the distribution pattern of BRTs in the CP of AD brains at various ages. Electron microscopy of negatively stained isolated BRTs revealed that these tangles are made of tightly packed bundles of long filaments with diameter around 10 nm that are morphologically distinct from the more loosely packed/shorter bundles of 6-8 nm amyloid fibrils of neuritic plaques (NPs) and from the 24 nm paired helical filaments of neurofibrillary tangles (NFTs) in AD brain. These data suggest that BRTs may represent a significant and measurable biomarker for AD in addition to NPs and NFTs. PMID:10375650

  14. Biondi ring tangles in the choroid plexus of Alzheimer's disease and normal aging brains: a quantitative study.

    PubMed

    Wen, G Y; Wisniewski, H M; Kascsak, R J

    1999-06-19

    The choroid plexus (CP) performs the vital function of producing up to 90% (450-1000 ml/day) of cerebrospinal fluid (CSF) to nourish and to protect the brain in the CSF suspension. The CP also acts as a selective barrier between blood and CSF to regulate ions and other essential molecules. However, the accumulation of intracellular inclusions called Biondi ring tangles (BRTs) in CP cells of Alzheimer's disease (AD)/aging brains may affect these vital functions of the CP. Statistical analysis of quantitative data on the numbers of CP cells containing BRTs from 54 brains (29 AD and 25 normal control), age range 1-100 years, indicated a significant difference (p<0.00004) between AD and control brains, using analysis of covariance (ANCOVA) with age as covariate. This study compiled the first set of archives to reveal the distribution pattern of BRTs in the CP of AD brains at various ages. Electron microscopy of negatively stained isolated BRTs revealed that these tangles are made of tightly packed bundles of long filaments with diameter around 10 nm that are morphologically distinct from the more loosely packed/shorter bundles of 6-8 nm amyloid fibrils of neuritic plaques (NPs) and from the 24 nm paired helical filaments of neurofibrillary tangles (NFTs) in AD brain. These data suggest that BRTs may represent a significant and measurable biomarker for AD in addition to NPs and NFTs.

  15. 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. PMID:24174656

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Inaudible high-frequency sounds affect brain activity: hypersonic effect.

    PubMed

    Oohashi, T; Nishina, E; Honda, M; Yonekura, Y; Fuwamoto, Y; Kawai, N; Maekawa, T; Nakamura, S; Fukuyama, H; Shibasaki, H

    2000-06-01

    Although it is generally accepted that humans cannot perceive sounds in the frequency range above 20 kHz, the question of whether the existence of such "inaudible" high-frequency components may affect the acoustic perception of audible sounds remains unanswered. In this study, we used noninvasive physiological measurements of brain responses to provide evidence that sounds containing high-frequency components (HFCs) above the audible range significantly affect the brain activity of listeners. We used the gamelan music of Bali, which is extremely rich in HFCs with a nonstationary structure, as a natural sound source, dividing it into two components: an audible low-frequency component (LFC) below 22 kHz and an HFC above 22 kHz. Brain electrical activity and regional cerebral blood flow (rCBF) were measured as markers of neuronal activity while subjects were exposed to sounds with various combinations of LFCs and HFCs. None of the subjects recognized the HFC as sound when it was presented alone. Nevertheless, the power spectra of the alpha frequency range of the spontaneous electroencephalogram (alpha-EEG) recorded from the occipital region increased with statistical significance when the subjects were exposed to sound containing both an HFC and an LFC, compared with an otherwise identical sound from which the HFC was removed (i.e., LFC alone). In contrast, compared with the baseline, no enhancement of alpha-EEG was evident when either an HFC or an LFC was presented separately. Positron emission tomography measurements revealed that, when an HFC and an LFC were presented together, the rCBF in the brain stem and the left thalamus increased significantly compared with a sound lacking the HFC above 22 kHz but that was otherwise identical. Simultaneous EEG measurements showed that the power of occipital alpha-EEGs correlated significantly with the rCBF in the left thalamus. Psychological evaluation indicated that the subjects felt the sound containing an HFC to be more

  1. Patterns of brain activity in normals and schizophrenics with positron emission tomography

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Gomez-Mont, F.; Brodie, J.D.; Canero, R.; Van Gelder, P.; Russell, J.A.G.

    1985-05-01

    The authors investigated the functional interaction among brain areas under baseline and upon activation by a visual task to compare the response of normal subjects from the ones of chronic schizophrenics. Cerebral metabolic images were obtained on twelve healthy volunteers an eighteen schizophrenics with positron emission tomography and 11-C-Deoxyglucose. Correlation coefficients among the relative metabolic values (region of interest divided by the average of whole brain gray matter) of 11 brain regions; frontal, parietal, temporal and occipital left and right lobes, left and right basal ganglia and thalamus were computed for the baseline and for the task. Under baseline, normals showed more functional correlations than schizophrenics. Both groups showed a thalamo-occipital (positive) and thalamo-frontal (negative) interaction. The highest correlations among homologous brain areas were the frontal, occipital and basal ganglia.

  2. 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.

  3. 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.

  4. CNS-disease affecting the heart: brain-heart disorders.

    PubMed

    Finsterer, Josef; Wahbi, Karim

    2014-10-15

    There are a number of hereditary and non-hereditary central nervous system (CNS) disorders, which directly or indirectly affect the heart (brain-heart disorders). The most well-known of these CNS-disorders are epilepsy, stroke, subarachanoid bleeding, bacterial meningitis, and head injury. In addition, a number of hereditary and non-hereditary neurodegenerative disorders may impair cardiac functions. Affection of the heart may manifest as arrhythmias, cardiomyopathy, or autonomic dysfunction. Rarer cardiac complications of CNS disorders include heart failure, systolic or diastolic dysfunction, myocardial infarction, arterial hypertension, or pulmonary hypertension. Cardiomyopathy induced by hereditary CNS disease mainly include stress-induced myocardial dysfunction, known as Takotsubo syndrome (TTS). CNS disease triggering TTS includes epilepsy, ischemic stroke, subarachnoid bleeding, or PRES syndrome. Arrhythmias induced by hereditary CNS disease include supraventricular or ventricular arrhythmias leading to palpitations, dizziness, vertigo, fainting, syncope, (near) sudden cardiac death, or sudden unexplained death in epilepsy (SUDEP). Appropriate management of cardiac involvement in CNS-disorders is essential to improve outcome of affected patients. PMID:25034054

  5. Maternal age affects brain metabolism in adult children of mothers affected by Alzheimer’s disease

    PubMed Central

    Mosconi, Lisa; Tsui, Wai; Murray, John; McHugh, Pauline; Li, Yi; Williams, Schantel; Pirraglia, Elizabeth; Glodzik, Lidia; De Santi, Susan; Vallabhajosula, Shankar; de Leon, Mony J.

    2011-01-01

    Cognitively normal (NL) individuals with a maternal history of late-onset Alzheimer’s disease (MH) show reduced brain glucose metabolism on FDG-PET as compared to those with a paternal history (PH) and those with negative family history (NH) of Alzheimer’s disease (AD). This FDG-PET study investigates whether metabolic deficits in NL MH are associated with advancing maternal age at birth. Ninety-six NL individuals with FDG-PET were examined, including 36 MH, 24 PH, and 36 NH. Regional-to-whole brain gray matter standardized FDG uptake value ratios were examined for associations with parental age across groups using automated regions-of-interest and statistical parametric mapping. Groups were comparable for clinical and neuropsychological measures. Brain metabolism in AD-vulnerable regions was lower in MH compared to NH and PH, and negatively correlated with maternal age at birth only in MH. There were no associations between paternal age and metabolism in any group. Evidence for a maternally inherited, maternal age-related mechanism provides further insight on risk factors and genetic transmission in late-onset AD. PMID:21514691

  6. Maternal age affects brain metabolism in adult children of mothers affected by Alzheimer's disease.

    PubMed

    Mosconi, Lisa; Tsui, Wai; Murray, John; McHugh, Pauline; Li, Yi; Williams, Schantel; Pirraglia, Elizabeth; Glodzik, Lidia; De Santi, Susan; Vallabhajosula, Shankar; de Leon, Mony J

    2012-03-01

    Cognitively normal (NL) individuals with a maternal history of late-onset Alzheimer's disease (MH) show reduced brain glucose metabolism on FDG-PET as compared to those with a paternal history (PH) and those with negative family history (NH) of Alzheimer's disease (AD). This FDG-PET study investigates whether metabolic deficits in NL MH are associated with advancing maternal age at birth. Ninety-six NL individuals with FDG-PET were examined, including 36 MH, 24 PH, and 36 NH. Regional-to-whole brain gray matter standardized FDG uptake value ratios were examined for associations with parental age across groups using automated regions-of-interest and statistical parametric mapping. Groups were comparable for clinical and neuropsychological measures. Brain metabolism in AD-vulnerable regions was lower in MH compared to NH and PH, and negatively correlated with maternal age at birth only in MH. There were no associations between paternal age and metabolism in any group. Evidence for a maternally inherited, maternal age-related mechanism provides further insight on risk factors and genetic transmission in late-onset AD.

  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. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas.

    PubMed

    van Dijk, A; Klanker, M; van Oorschot, N; Post, R; Hamelink, R; Feenstra, M G P; Denys, D

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC. PMID:23900312

  9. MEG brain activities reflecting affection for visual food stimuli.

    PubMed

    Kuriki, Shinya; Miyamura, Takahiro; Uchikawa, Yoshinori

    2010-01-01

    This study aimed to explore the modulation of alpha rhythm in response to food pictures with distinct affection values. We examined the method to discriminate subject's state, i.e., whether he/she liked the article of food or not, from MEG signals detected over the head. Pictures of familiar foods were used as affective stimuli, while those pictures with complementary color phase were used as non-affective stimuli. Alpha band signals in a narrow frequency window around the spectral peak of individual subjects were wavelet analyzed and phase-locked component to the stimulus onset was obtained as a complex number. The amplitude of the phase-locked component was averaged during 0-1 s after stimulus onset for 30 epochs in a measurement session and across 76 channels of MEG sensor. In statistical test of individual subjects, significant difference was found in the real part of the averaged phase-locked amplitude between the normal-color and reverse-color pictures. These results suggest that affective information processing of food pictures is reflected in the synchronized component of narrow band alpha rhythm. PMID:21096510

  10. 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.

  11. Whole brain N-acetylaspartate concentration is conserved throughout normal aging

    PubMed Central

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

    2011-01-01

    We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker - the amino acid derivative N-acetylaspartate (NAA). To test this we obtained the whole-brain and whole-head NAA concentration (WBNAA and WHNAA), with proton MR spectroscopy; and the fractional brain parenchyma volume (fBPV) – a metric of atrophy, by segmenting the MRI from 42 (18 male) healthy young (31.9±5.8 years-old) and 100 (64 male, 72.6±7.3 years-old) cognitively-normal elderly. The 12.8±1.9 mM WBNAA of the young was not significantly different from the 13.1±3.1 mM in the elderly (p>0.05). In contrast, both fBPV (87.3±4.7% versus 74.8±4.8%) and WHNAA (11.1±1.7 mM versus 9.8±2.4 mM) were significantly higher in the young (~14%, p<.0001 for both). The similarity in mean WBNAA between two cohorts 4 decades of normal aging apart suggests that neuronal integrity is maintained across the lifespan. Clinically, WBNAA could be used as a marker for normal (hence, also abnormal) brain aging. In contrast, WHNAA and fBPV seem age-related suggesting that brain atrophy may occur without compromising the remaining tissue. PMID:22245316

  12. 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 using similar NCV…

  13. 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

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

    PubMed

    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

    2016-07-01

    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

  15. 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…

  16. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery.

    PubMed

    Han, Eun Young; Zhang, Xin; Yan, Yulong; Sharma, Sunil; Penagaricano, Jose; Moros, Eduardo; Corry, Peter

    2012-01-01

    At the University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  17. 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.

  18. Normalization.

    ERIC Educational Resources Information Center

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  19. Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

    PubMed

    Yokoyama, Jennifer S; Lee, Allen K L; Takada, Leonel T; Busovaca, Edgar; Bonham, Luke W; Chao, Steven Z; Tse, Marian; He, Jing; Schwarz, Christopher G; Carmichael, Owen T; Matthews, Brandy R; Karydas, Anna; Weiner, Michael W; Coppola, Giovanni; DeCarli, Charles S; Miller, Bruce L; Rosen, Howard J

    2015-01-01

    Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer's disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ε4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ε4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ε4 and being Chinese. The APOE ε4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (Puncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (Puncorrected<0.01), all regions that are associated with neurodegeneration in AD. After correction for multiple testing, the left cuneus remained significantly associated with the interaction effect (PFWE = 0.05). Our study suggests there is a differential effect of APOE ε4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ε4 effects on the brain in diverse populations. PMID:25738563

  20. Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects.

    PubMed

    Glenn, Thomas C; Martin, Neil A; Horning, Michael A; McArthur, David L; Hovda, David A; Vespa, Paul; Brooks, George A

    2015-06-01

    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-(2)H2]glucose, that is, D2-glucose, and [3-(13)C]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 (13)CO2 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-(13)C]lactate tracer and (13)C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75-80% of (13)CO2 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

  1. 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

  2. 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.

  3. 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. PMID:23183749

  4. 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

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

    PubMed

    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.

  6. Autofluorescence of normal and neoplastic human brain tissue: an aid for intraoperative delineation of tumor resection margins

    NASA Astrophysics Data System (ADS)

    Bottiroli, Giovanni F.; Croce, Anna C.; Locatelli, Donata; Nano, Rosanna; Giombelli, Ermanno; Messina, Alberto; Benericetti, Eugenio

    1998-01-01

    Light-induced autofluorescence measurements were made on normal and tumor brain tissues to assess their spectroscopic properties and to verify the potential of this parameter for an intraoperative delineation of tumor resection margins. Spectrofluorometric analysis was performed both at the microscope on tissue sections from surgical resection, and on patients affected by glioblastoma, during surgical operation. Significant differences in autofluorescence emission properties were found between normal and tumor tissues in both ex vivo and in vivo measurements, indicating that the lesion can be distinguished from the informal surrounding tissues by the signal amplitude and the spectral shape. The non-invasiveness of the technique opens interesting prospects for improving the efficacy of neurosurgical operation, by allowing an intraoperative delimitation of tumor resection margins.

  7. 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

  8. 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.

  9. Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency.

    PubMed

    Bohatschek, M; Werner, A; Raivich, G

    2001-11-01

    The lipopolysaccharide (LPS) constituents of the gram-negative bacterial wall are among the most potent activators of inflammation. In the current study, we examined the effect of subcutaneous injection of Escherichia coli LPS on leukocyte influx into the normal and injured brain using endogenous peroxidase (EP). Normal brain parenchyma does not contain granulocytes and this does not change after indirect trauma, in facial axotomy. However, systemic injection of 1 mg LPS led to a gradual appearance of EP-positive parenchymal granulocytes within 12 h, with a maximum at 1-4 days after injection. Facial axotomy (day 14) led to a further 50-300% increase in granulocyte number. Of the five mouse strains tested in the current study, four--Balb/C, FVB, C57Bl/6, and C3H/N--showed vigorous granulocyte influx (60-90 cells per 20-microm section in axotomized facial nucleus, 20-40 cells per section on the contralateral side). The influx was an order of magnitude lower in the SJL mice. The peroxidase-positive cells were immunoreactive for neutrophil antigen 7/4 and alpha M beta 2 integrin, were negative for IBA1 (monocytes) and CD3 (T cells), and could be prelabeled by subcutaneous injection with rhodamine B isothiocyanate (RITC), confirming their origin as blood-borne granulocytes. All RITC-positive cells were IBA1 negative. This influx of granulocytes was accompanied by a disruption of the blood-brain barrier to albumin and induction of the cell adhesion molecule ICAM-1 on affected blood vessels. Transgenic deletion of ICAM-1 led to a more than 50% reduction in the number of infiltrating granulocytes compared to litter-matched wild-type controls, in normal brain as well as in axotomized facial motor nucleus. In summary, systemic injection of LPS leads to invasion of granulocytes into the mouse brain and a breakdown of the blood-brain barrier to blood-borne cells and to soluble molecules. Moreover, this mechanism may play a pathogenic role in the etiology of meningitis and in

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Imaging brain effects of APOE4 in cognitively normal individuals across the lifespan.

    PubMed

    Fouquet, Marine; Besson, Florent L; Gonneaud, Julie; La Joie, Renaud; Chételat, Gaël

    2014-09-01

    The ε4 allele of the apolipoprotein E (APOE4) is associated with an increased risk of developing Alzheimer's disease (AD). Hence, several studies have compared the brain characteristics of APOE4 carriers versus non-carriers in presymptomatic stages to determine early AD biomarkers. The present review provides an overview on APOE4-related brain changes in cognitively normal individuals, focusing on the main neuroimaging biomarkers for AD, i.e. cortical beta-amyloid (Aβ) deposition, hypometabolism and atrophy. The most consistent findings are observed with Aβ deposition as most studies report significantly higher cortical Aβ load in APOE4 carriers compared with non-carriers. Fluorodeoxyglucose-positron emission tomography studies are rare and tend to show hypometabolism in brain regions typically impaired in AD. Structural magnetic resonance imaging findings are the most numerous and also the most discrepant, showing atrophy in AD-sensitive regions in some studies but contradicting results as well. Altogether, this suggests a graded effect of APOE4, with a predominant effect on Aβ over brain structure and metabolism. Multimodal studies confirm this view and also suggest that APOE4 effects on brain structure and function are mediated by both Aβ-dependent and Aβ-independent pathological processes. Neuroimaging studies on asymptomatic APOE4 carriers offer relevant information to the understanding of early pathological mechanisms of the disease, although caution is needed as to whether APOE4 effects reflect AD pathological processes, and are representative of these effects in non-carriers.

  19. Expression and distribution of carboxypeptidase B in the hippocampal subregions of normal and Alzheimer's disease brain.

    PubMed

    Papp, Henrietta; Török, I; Matsumoto, A; Enomoto, T; Matsuyama, S; Kása, P

    2003-01-01

    Earlier neurochemical studies suggested that human brain carboxypeptidase B may play a significant role in the degradation of amyloid-beta1-42 in the brain. Using an immimohistochemical technique we report here on the neuronal expression and distribution of this enzyme in the segments (CA1a, CA1b and CA1c) of the CA1 subfield and in area CA4 of the hippocampus in normal and Alzheimer's disease brain samples. Its distribution was compared with the appearance of neurofibrillary tangles in the same brain sample. For immunohistochemical localization of carboxypeptidase B, a specific C14-module antibody was applied, together with the Gallyas silver impregnation technique for the demonstration of neurofibrillary tangles. The results revealed that, in the control samples, most of the immunoreactivity appeared in segment CA1a in the pyramidal cells, less in segment CA1b and least in segment CA1c. In the Alzheimer's disease samples, there was no particular immunostaining in the neurons, but, a large number of silver-impregnated degenerated neurons appeared. The results support the suggestion that carboxypeptidase B may play a significant role in elimination of the intracellular accumulation and toxicity of amyloid-beta in the human brain and thereby protect the neurons from degeneration. PMID:12705322

  20. Towards adapting a normal patient database for SPECT brain perfusion imaging

    NASA Astrophysics Data System (ADS)

    Smith, N. D.; Holmes, R. B.; Soleimani, M.; Evans, M. J.; Cade, S. C.; Mitchell, C. N.

    2012-06-01

    Single-photon emission computerized tomography (SPECT) is a tool which can be used to image perfusion in the brain. Clinicians can use such images to help diagnose dementias such as Alzheimer's disease. Due to the intrinsic stochasticity in the photon imaging system, some form of statistical comparison of an individual image with a 'normal' patient database gives a clinician additional confidence in interpreting the image. Due to the variations between SPECT camera systems, ideally a normal patient database is required for each individual system. However, cost or ethical considerations often prohibit the collection of such a database for each new camera system. Some method of adapting existing normal patient databases to new camera systems would be beneficial. This paper introduces a method which may be regarded as a 'first-pass' attempt based on 2-norm regularization and a codebook of discrete spatially stationary convolutional kernels. Some preliminary illustrative results are presented, together with discussion on limitations and possible improvements.

  1. Statistical parametric mapping demonstrates asymmetric uptake with Tc-99m ECD and Tc-99m HMPAO SPECT in normal brain.

    PubMed

    Brinkmann, Benjamin H; Jones, David T; Stead, Matt; Kazemi, Noojan; O'Brien, Terence J; So, Elson L; Blumenfeld, Hal; Mullan, Brian P; Worrell, Gregory A

    2012-01-01

    Tc-99m ethyl cysteinate diethylester (ECD) and Tc-99m hexamethyl propylene amine oxime (HMPAO) are commonly used for single-photon emission computed tomography (SPECT) studies of a variety of neurologic disorders. Although these tracers have been very helpful in diagnosing and guiding treatment of neurologic disease, data describing the distribution and laterality of these tracers in normal resting brain are limited. Advances in quantitative functional imaging have demonstrated the value of using resting studies from control populations as a baseline to account for physiologic fluctuations in cerebral perfusion. Here, we report results from 30 resting Tc-99m ECD SPECT scans and 14 resting Tc-99m HMPAO scans of normal volunteers with no history of neurologic disease. Scans were analyzed with regions of interest and with statistical parametric mapping, with comparisons performed laterally (left vs. right), as well as for age, gender, and handedness. The results show regions of significant asymmetry in the normal controls affecting widespread areas in the cerebral hemispheres, but most marked in superior parietotemporal region and frontal lobes. The results have important implications for the use of normal control SPECT images in the evaluation of patients with neurologic disease.

  2. Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks.

    PubMed

    Guye, Maxime; Bettus, Gaelle; Bartolomei, Fabrice; Cozzone, Patrick J

    2010-12-01

    Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits "small-world" properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer's disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies. PMID:20349109

  3. 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

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

    PubMed

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

    2015-07-01

    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

  5. Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

    PubMed Central

    Moreno-López, Laura; Soriano-Mas, Carles; Delgado-Rico, Elena; Rio-Valle, Jacqueline S.; Verdejo-García, Antonio

    2012-01-01

    Introduction Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. Methods Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex). Results Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. Conclusion Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation. PMID:23185306

  6. HFE polymorphisms affect survival of brain tumor patients.

    PubMed

    Lee, Sang Y; Slagle-Webb, Becky; Sheehan, Jonas M; Zhu, Junjia; Muscat, Joshua E; Glantz, Michael; Connor, James R

    2015-03-01

    The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.

  7. 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

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

    PubMed

    Kolta, M G; Soliman, K F; Williams, B B

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta E) and immunoreactive insulin (IRI) 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) 3 days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for 3 days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) 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.

  9. 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.

  10. Nonlinear time course of brain volume loss in cognitively normal and impaired elders

    PubMed Central

    Schuff, Norbert; Tosun, Duygu; Insel, Philip S.; Chiang, Gloria C.; Truran, Diana; Aisen, Paul S.; Jack, Clifford R; Weiner, Michael W.

    2010-01-01

    The goal was to elucidate the time course of regional brain atrophy rates relative to age in cognitively normal (CN) aging, mild cognitively impairment (MCI) and Alzheimer’s disease (AD), without a-priori models for atrophy progression. Regional brain volumes from 147 CN subjects, 164 stable MCI, 93 MCI-to-AD converters and 111 AD patients, between 51 to 91 years old and who had repeated 1.5T magnetic resonance imaging (MRI) scans over 30 months, were analyzed. Relations between regional brain volume change and age were determined using generalized additive models, an established non-parametric concept for approximating nonlinear relations. Brain atrophy rates varied nonlinearly with age, predominantly in regions of the temporal lobe. Moreover, the atrophy rates of some regions leveled off with increasing age in control and stable MCI subjects whereas those rates progressed further in MCI-to-AD converters and AD patients. The approach has potential uses for early detection of AD and differentiation between stable and progressing MCI. PMID:20855131

  11. Comparison of various methods for delivering radiolabeled monoclonal antibody to normal rat brain

    SciTech Connect

    Bullard, D.E.; Bourdon, M.; Bigner, D.D.

    1984-11-01

    Different methods were evaluated for delivering iodine-125 monoclonal antibodies (Mab's) to the central nervous system in 40- to 99-gm Fischer rats. By evaluating interhemispheric, interregional, and brain:blood ratios of Mab's, the efficacy of intracarotid (IC) or intravenous (IV) administration of Mab's with and without prior IC perfusion with 0.9% NaCl (normal saline, NS), 1.4 M mannitol, or 1.6 M arabinose, or of femoral artery perfusion with 1.4 M mannitol was evaluated. No difference was seen between IC and IV administration of Mab's with or without prior perfusion. Intracarotid perfusion with hyperosmolar agents was required to disrupt the blood-brain barrier (BBB) and to significantly elevate brain levels of Mab's. Temporally, following hyperosmolar BBB disruption, brain:blood Mab ratios remained elevated bilaterally at 7 days after Mab delivery, with the ipsilateral hemispheric levels remaining significantly elevated compared with the contralateral hemispheric levels until Day 5, when the ratio returned to the nonperfused range. Catheterization was required in the small animals and was performed under magnification in 10 to 20 minutes, with less than an 8% overall morbidity and mortality.

  12. Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome

    PubMed Central

    Blain-Moraes, Stefanie; Boshra, Rober; Ma, Heung Kan; Mah, Richard; Ruiter, Kyle; Avidan, Michael; Connolly, John F.; Mashour, George A.

    2016-01-01

    Up to 40% of individuals with unresponsive wakefulness syndrome (UWS) actually might be conscious. Recent attempts to detect covert consciousness in behaviorally unresponsive patients via neurophysiological patterns are limited by the need to compare data from brain-injured patients to healthy controls. In this report, we pilot an alternative within-subject approach by using propofol to perturb the brain state of a patient diagnosed with UWS. An auditory stimulation series was presented to the patient before, during, and after exposure to propofol while high-density electroencephalograph (EEG) was recorded. Baseline analysis revealed residual markers in the continuous EEG and event-related potentials (ERPs) that have been associated with conscious processing. However, these markers were significantly distorted by the patient’s pathology, challenging the interpretation of their functional significance. Upon exposure to propofol, changes in EEG characteristics were similar to what is seen in healthy individuals and ERPs associated with conscious processing disappeared. At the 1-month follow up, the patient had regained consciousness. We offer three alternative explanations for these results: (1) the patient was covertly consciousness, and was anesthetized by propofol administration; (2) the patient was unconscious, and the observed EEG changes were a propofol-specific phenomenon; and (3) the patient was unconscious, but his brain networks responded normally in a way that heralded the possibility of recovery. These alternatives will be tested in a larger study, and raise the intriguing possibility of using a general anesthetic as a probe of brain states in behaviorally unresponsive patients. PMID:27313518

  13. 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.

  14. Normalization of coagulopathy is associated with improved outcome after isolated traumatic brain injury.

    PubMed

    Epstein, Daniel S; Mitra, Biswadev; Cameron, Peter A; Fitzgerald, Mark; Rosenfeld, Jeffrey V

    2016-07-01

    Acute traumatic coagulopathy (ATC) has been reported in the setting of isolated traumatic brain injury (iTBI) and is associated with poor outcomes. We aimed to evaluate the effectiveness of procoagulant agents administered to patients with ATC and iTBI during resuscitation, hypothesizing that timely normalization of coagulopathy may be associated with a decrease in mortality. A retrospective review of the Alfred Hospital trauma registry, Australia, was conducted and patients with iTBI (head Abbreviated Injury Score [AIS] ⩾3 and all other body AIS <3) and coagulopathy (international normalized ratio ⩾1.3) were selected for analysis. Data on procoagulant agents used (fresh frozen plasma, platelets, cryoprecipitate, prothrombin complex concentrates, tranexamic acid, vitamin K) were extracted. Among patients who had achieved normalization of INR or survived beyond 24hours and were not taking oral anticoagulants, the association of normalization of INR and death at hospital discharge was analyzed using multivariable logistic regression analysis. There were 157 patients with ATC of whom 68 (43.3%) received procoagulant products within 24hours of presentation. The median time to delivery of first products was 182.5 (interquartile range [IQR] 115-375) minutes, and following administration of coagulants, time to normalization of INR was 605 (IQR 274-1146) minutes. Normalization of INR was independently associated with significantly lower mortality (adjusted odds ratio 0.10; 95% confidence interval 0.03-0.38). Normalization of INR was associated with improved mortality in patients with ATC in the setting of iTBI. As there was a substantial time lag between delivery of products and eventual normalization of coagulation, specific management of coagulopathy should be implemented as early as possible. PMID:26947341

  15. Anatomy and metabolism of the normal human brain studied by magnetic resonance at 1. 5 Tesla

    SciTech Connect

    Bottomley, P.A.; Hart, H.R. Jr.; Edelstein, W.A.; Schenck, J.F.; Smith, L.S.; Leue, W.M.; Mueller, O.M.; Redington, R.W.

    1984-02-01

    Proton magnetic resonance (MR) images were obtained of the human head in magnetic fields as high as 1.5 Tesla (T) using slotted resonator high radio-frequency (RF) detection coils. The images showed no RF field penetration problems and exhibited an 11 (+/-1)-fold improvement in signal-to-noise ratio over a .12-T imaging system. The first localized phosphorus 31, carbon 13, and proton MR chemical shift spectra recorded with surface coils from the head and body in the same instrument showed relative concentrations of phosphorus metabolites, triglycerides, and, when correlated with proton images, negligible lipid (-CH/sub 2/-) signal from brain tissue on the time scale of the imaging experiment. Sugar phosphate and phosphodiester concentrations were significantly elevated in the head compared with muscle. This method should allow the combined assessment of anatomy, metabolism, and biochemistry in both the normal and diseased brain.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. Anti-saccade performance predicts executive function and brain structure in normal elders

    PubMed Central

    Mirsky, Jacob B.; Heuer, Hilary W.; Jafari, Aria; Kramer, Joel H.; Schenk, Ana K.; Viskontas, Indre V.; Neuhaus, John; Miller, Bruce L.; Boxer, Adam L.

    2013-01-01

    Objective To assess the neuropsychological and anatomical correlates of anti-saccade (AS) task performance in normal elders. Background The AS task correlates with neuropsychological measures of executive function and frontal lobe volume in neurological diseases, but has not been studied in a well-characterized normal elderly population. Because executive dysfunction can indicate an increased risk for cognitive decline in cognitively normal elders, we hypothesized that AS performance might be a sensitive test of age-related processes that impair cognition. Method The percentage of correct AS responses was evaluated in forty-eight normal elderly subjects and compared with neuropsychological test performance using linear regression analysis and gray matter volume measured on MRI scans using voxel-based morphometry. Results The percentage of correct AS responses was associated with measures of executive function, including modified trails, design fluency, Stroop inhibition, abstraction, and backward digit span, and correlated with gray matter volume in two brain regions involved in inhibitory control: the left inferior frontal junction and the right supplementary eye field. The association of AS correct responses with neuropsychological measures of executive function was strongest in individuals with fewer years of education. Conclusions The AS task is sensitive to executive dysfunction and frontal lobe structural alterations in normal elders. PMID:21697711

  1. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain.

    PubMed

    Egorova, Natalia; Gollub, Randy L; Kong, Jian

    2015-01-01

    Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG), medial frontal cortex (MFC) and bilateral hippocampus (Hpc). We demonstrate that the PAG-MFC and PAG-Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham) is related to the modulation of PAG-MFC and PAG-Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory. PMID:26594625

  2. 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.

  3. Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects.

    PubMed

    Lucht, Michael J; Barnow, Sven; Sonnenfeld, Christine; Rosenberger, Albert; Grabe, Hans Joergen; Schroeder, Winnie; Völzke, Henry; Freyberger, Harald J; Herrmann, Falko H; Kroemer, Heyo; Rosskopf, Dieter

    2009-08-01

    Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ. PMID:19376182

  4. Transplanted transgenically marked oligodendrocytes survive, migrate and myelinate in the normal mouse brain as they do in the shiverer mouse brain.

    PubMed

    Lachapelle, F; Duhamel-Clerin, E; Gansmüller, A; Baron-Van Evercooren, A; Villarroya, H; Gumpel, M

    1994-05-01

    The dye Hoechst 33342 was combined with an immunodetectable transgene product (chloramphenicol acetyltransferase, CAT) expressed in differentiated oligodendrocytes to trace their fate after transplantation in the normal and the shiverer mouse brain. In the shiverer brain, the technique allowed us to visualize grafted cells inside myelin basic protein-positive myelin patches. Most of these cells were CAT-positive/Hoechst 33342-negative, reinforcing our hypothesis that cell division probably follows migration of grafted oligodendrocytes. Correlation of their morphology and distribution with their location in the host CNS suggested a local effect on the cell division and morphogenesis of the grafted material. When compared with transplantation of fragments of normal newborn donor tissue into the newborn shiverer brain, no difference could be seen between the behaviour of normal and transgenic oligodendrocytes. In the normal brain, transgenic oligodendrocytes survived at least 150 days and successfully myelinated the host axons. The timing of differentiation of grafted cells was similar in both types of recipient brains. Migration occurred rostrally and caudally. Although migrating cells could be observed along the meninges and the blood vessels, migration occurred preferentially along white matter tracts. The extent of migration was influenced by the site of implantation, and grafted cells could be found up to 6 mm from the grafting point. No differences in the timing of differentiation or the pattern or extent of migration could thus be demonstrated when transgenic oligodendrocytes were transplanted in the normal or the shiverer brain. This validates our previous studies using the newborn shiverer mouse as recipient.

  5. 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. PMID:23423504

  6. 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.

  7. 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.

  8. 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. PMID:25847861

  9. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    PubMed

    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.

  10. A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function.

    PubMed

    Safaeian, Navid; David, Tim

    2013-10-01

    The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging.

  11. 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

  12. Brain regions and genes affecting limb-clasping responses.

    PubMed

    Lalonde, R; Strazielle, C

    2011-06-24

    Adult rodents picked up by the tail and slowly descending towards a horizontal surface extend all four limbs in anticipation of contact. Mouse mutants with pathologies in various brain regions and the spinal cord display instead a flexion response, often characterized by paw-clasping and a bat-like posture. These phenotypes are observed in mice with lesions in cerebellum, basal ganglia, and neocortex, as well as transgenic models of Alzheimer's disease. The underlying mechanism appears to include cerebello-cortico-reticular and cortico-striato-pallido-reticular pathways, possibly triggered by changes in noradrenaline and serotonin transmission.

  13. Proprioceptive neuropathy affects normalization of the H-reflex by exercise after spinal cord injury

    PubMed Central

    Ollivier-Lanvin, Karen; Keeler, Benjamin E.; Siegfried, Rachel; Houlé, John D.; Lemay, Michel A.

    2009-01-01

    The H-reflex habituates at relatively low frequency (10 Hz) stimulation in the intact spinal cord, but loss of descending inhibition resulting from spinal cord transection reduces this habituation. There is a return towards a normal pattern of low-frequency habituation in the reflex activity with cycling exercise of the affected hind limbs. This implies that repetitive passive stretching of the muscles in spinalized animals and the accompanying stimulation of large (Group I and II) proprioceptive fibers has modulatory effects on spinal cord reflexes after injury. To test this hypothesis, we induced pyridoxine neurotoxicity that preferentially affects large dorsal root ganglia neurons in intact and spinalized rats. Pyridoxine or saline injections were given twice daily (IP) for 6 weeks and half of the spinalized animals were subjected to cycling exercise during that period. After 6 weeks, the tibial nerve was stimulated electrically and recordings of M and H waves were made from interosseous muscles of the hind paw. Results show that pyridoxine treatment completely eliminated the H-reflex in spinal intact animals. In contrast, transection paired with pyridoxine treatment resulted in a reduction of the frequency-dependent habituation of the H-reflex that was not affected by exercise. These results indicate that normal Group I and II afferent input is critical to achieve exercise-based reversal of hyper-reflexia of the H-reflex after spinal cord injury. PMID:19913536

  14. Affective State and Community Integration after Traumatic Brain Injury

    PubMed Central

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

    2014-01-01

    Previous studies investigating the relationship between affective state and community integration have focused primarily on the influence of depression and anxiety. Additionally, 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 TBI among participants with and without a current major depressive episode. Sixty-four community-dwelling participants with a history of complicated mild to severe TBI participated in this cross-sectional cohort study. High positive affect contributed significantly to frequency of participation (β=.401, p=.001), and both high positive affect and low negative affect significantly contributed to better satisfaction with participation (F2,61=13.63, p<.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 TBI and incorporating a subjective measure of participation when considering community integration outcomes. PMID:25133618

  15. 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.

  16. 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.

  17. 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. PMID:2529204

  18. Relationship of mercury to cognitive, affective and perceptual motor functioning in a normal sample in Hawaii

    SciTech Connect

    Sine, L.F.

    1983-01-01

    Although the effects of toxic levels of mercury have been well documented, the effects of subclinical levels of mercury on normal populations have generally not been studied. The purpose of this investigation was to assess the impact of mercury risk factors on cognition, affect, psychopathology, and known mercury-related symptoms in a normal sample in Hawaii exposed to subclinical although elevated levels of elemental mercury through inhalation associated with volcanic activity and of methylmercury mostly through ingestion of large ocean species fish. The following summarizes the findings and conclusions of the study: 1) a four week test-retest reliability using 41 of the subjects showed that the 41 measures used in the study exhibited an average correlation of .78. Using all 413 subjects, the average internal consistency measured by Cronbach's ..cap alpha.. was .82 for the 17 affect, psychopathology, and symptom measures; 2) nine mercury source variables were used to predict the amount of total mercury in hair. Interestingly, none of the source variables predicted hair total mercury; 3) the source variables in addition to hair total mercury and statistical control variables were used to predict the twenty-two functioning variables in the four domains cited above with a relative absence of relationships noted. This finding indicates that the normal population in Hawaii appears not to be at risk; and 4) one historical mercury source variable, reported fish intake when young, related to six functioning variables - the psychopathology measures of Somatization, Obsessive-Compulsive and Anxiety as well as the Sensory, Affect and Mental symptoms - with Beta weights in the .15 to .20 range. The implications of the findings were discussed and suggestions offered for future research especially with respect to specific high risk subgroups.

  19. 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

  20. 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.

  1. Brain responses during sentence reading: visual input affects central processes.

    PubMed

    Gunter, T C; Friederici, A D; Hahne, A

    1999-10-19

    The effect of visual contrast on sentence reading was investigated using event-related brain potentials (ERPs). Under the low contrast condition semantic integration as reflected in the N400 ERP component was delayed to some degree. The left anterior negativity (LAN) reflecting initial syntactic processes, in contrast, seemed to change its characteristics as a function of visual input. In the high contrast condition the LAN preceded the P200 component whereas in the low contrast condition it was present after this component. These ERP-data from word-by-word sentence reading together with prior results from sentence listening suggest that the physical characteristics of the input must fall within a certain optimal range to guarantee ERP-effects of fast initial syntactic processes.

  2. Pathological display of affect in patients with depression and right frontal brain damage. An alternative mechanism.

    PubMed

    Ross, E D; Stewart, R S

    1987-03-01

    Two patients are reported with the acute onset of pathological crying following right inferior frontal brain damage. Both had severe endogenous depression and neither had pseudobulbar palsy. These and other cases argue that two organic brain diseases--one structural and the other "physiopharmacological"--may interact to produce pathological display of affect that cannot be accounted for by traditional neurological explanations. A pharmacological mechanism for the rapid amelioration of pathological affect by tricyclic medications and its possible relationship to the newly discovered descending motor systems of the brain that use norepinephrine and serotonin as neurotransmitters is offered. These cases also suggest that pathological affect is a valuable clinical indicator of an underlying major depression in some brain-injured patients. PMID:3819712

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

    PubMed

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

    2015-01-01

    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. PMID:26580604

  4. 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.

  5. 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.

  6. Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis.

    PubMed

    Hyder, Fahmeed; Herman, Peter; Bailey, Christopher J; Møller, Arne; Globinsky, Ronen; Fulbright, Robert K; Rothman, Douglas L; Gjedde, Albert

    2016-05-01

    Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with (31)P and (13)C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements. PMID:26755443

  7. 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.

  8. cdk4 Deficiency Inhibits Skin Tumor Development but Does Not Affect Normal Keratinocyte Proliferation

    PubMed Central

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

    2002-01-01

    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. PMID:12163365

  9. Brain systems for assessing the affective value of faces.

    PubMed

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

    2011-06-12

    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.

  10. 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. PMID:25992074

  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. Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

    PubMed

    Pardo, José V; Lee, Joel T; Sheikh, Sohail A; Surerus-Johnson, Christa; Shah, Hemant; Munch, Kristin R; Carlis, John V; Lewis, Scott M; Kuskowski, Michael A; Dysken, Maurice W

    2007-04-15

    Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. PMID:17321756

  13. Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory Conditions

    PubMed Central

    Podojil, Joseph R.; Miller, Stephen D.; Miller, Richard J.

    2016-01-01

    The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 acting via its G-protein coupled receptor (GPCR) CXCR4 has been implicated in neurogenesis, neuromodulation, brain inflammation, HIV-1 encephalopathy and tumor growth. CXCR7 was identified as an alternate receptor for SDF-1/CXCL12. Characterization of CXCR7-deficient mice demonstrated a role for CXCR7 in fetal endothelial biology, cardiac development, and B-cell localization. Despite its ligand binding properties, CXCR7 does not seem to signal like a conventional GPCR. It has been suggested that CXCR7 may not function alone but in combination with CXCR4. Here, we investigated the regional localization of CXCR7 receptors in adult mouse brain using CXCR7-EGFP transgenic mice. We found that the receptors were expressed in various brain regions including olfactory bulb, cerebral cortex, hippocampus, subventricular zone (SVZ), hypothalamus and cerebellum. Extensive CXCR7 expression was associated with cerebral blood vessels. Using cell type specific markers, CXCR7 expression was found in neurons, astrocytes and oligodendrocyte progenitors. GAD-expressing neurons exhibited CXCR7 expression in the hippocampus. Expression of CXCR7 in the dentate gyrus included cells that expressed nestin, GFAP and cells that appeared to be immature granule cells. In mice with Experimental Autoimmune Encephalomyelitis (EAE), CXCR7 was expressed by migrating oligodendrocyte progenitors in the SVZ. We then compared the distribution of SDF-1/CXCL12 and CXCR7 using bitransgenic mice expressing both CXCR7-EGFP and SDF-1-mRFP. Enhanced expression of SDF-1/CXCL12 and CXCR7 was observed in the corpus callosum, SVZ and cerebellum. Overall, the expression of CXCR7 in normal and pathological nervous system suggests CXCR4-independent functions of SDF-1/CXCL12 mediated through its interaction with CXCR7. PMID:25997895

  14. Age and Gender Related Changes in the Normal Human Brain using Hybrid Diffusion Imaging (HYDI)

    PubMed Central

    Wu, Yu-Chien; Field, Aaron S.; Whalen, Paul J.; Alexander, Andrew L.

    2011-01-01

    Diffusion tensor imaging has been widely used to study brain diseases, disorders, development and aging. However, few studies have explored the effects of aging on diffusion imaging measures with higher b-values. Further the water diffusion in biological tissues appears bi-exponential although this also has not been explored with aging. In this study, hybrid diffusion imaging (HYDI) was used to study fifty-two healthy subjects with an age range from 18 to 72 years. The HYDI diffusion-encoding scheme consisted of five concentric q-space shells with b-values raging from 0 to 9375 s/mm2. Quantitative diffusion measures were investigated as a function of age and gender using both region-of-interest (whole brain white matter, genu and splenium of corpus callosum, posterior limb of the internal capsule) and whole-brain voxel based analyses. Diffusion measures included measures of the diffusion probability density function (zero displacement probability, and mean squared displacement), bi-exponential diffusion (i.e. volume fractions of fast/slow diffusion compartments and fast/slow diffusivities), and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity). The bi-exponential volume fraction, the fast diffusivity, and the axial diffusivity measures (f1, D1 and Da) were found to be more sensitive to normal aging than the restricted, slow and radial diffusion measures (Po, D2 and Dr). The bi-exponential volume fraction, f1, showed the most widespread age-dependence in the voxel-based analyses although both FA and mean diffusivity did show changes in frontal white matter regions that may be associated with age-related decline. PMID:20932911

  15. Local brain atrophy accounts for functional activity differences in normal aging.

    PubMed

    Kalpouzos, Grégoria; Persson, Jonas; Nyberg, Lars

    2012-03-01

    Functional brain imaging studies of normal aging typically show age-related under- and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under- and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under- as well as overrecruitment.

  16. 'Oops!': performance correlates of everyday attentional failures in traumatic brain injured and normal subjects.

    PubMed

    Robertson, I H; Manly, T; Andrade, J; Baddeley, B T; Yiend, J

    1997-06-01

    Insufficient attention to tasks can result in slips of action as automatic, unintended action sequences are triggered inappropriately. Such slips arise in part from deficits in sustained attention, which are particularly likely to happen following frontal lobe and white matter damage in traumatic brain injury (TBI). We present a reliable laboratory paradigm that elicits such slips of action and demonstrates high correlations between the severity of brain damage and relative-reported everyday attention failures in a group of 34 TBI patients. We also demonstrate significant correlations between self- and informant-reported everyday attentional failures and performance on this paradigm in a group of 75 normal controls. The paradigm (the Sustained Attention to Response Task-SART) involves the withholding of key presses to rare (one in nine) targets. Performance on the SART correlates significantly with performance on tests of sustained attention, but not other types of attention, supporting the view that this is indeed a measure of sustained attention. We also show that errors (false presses) on the SART can be predicted by a significant shortening of reaction times in the immediately preceding responses, supporting the view that these errors are a result of 'drift' of controlled processing into automatic responding consequent on impaired sustained attention to task. We also report a highly significant correlation of -0.58 between SART performance and Glasgow Coma Scale Scores in the TBI group.

  17. Maternal seizures can affect the brain developing of offspring.

    PubMed

    Cossa, Ana Carolina; Lima, Daiana Correia; do Vale, Tiago Gurgel; de Alencar Rocha, Anna Karynna Alves; da Graça Naffah-Mazzacoratti, Maria; da Silva Fernandes, Maria José; Amado, Debora

    2016-08-01

    To elucidate the impact of maternal seizures in the developing rat brain, pregnant Wistar rats were subjected to the pilocarpine-induced seizures and pups from different litters were studied at different ages. In the first 24 h of life, blood glucose and blood gases were analyzed. (14)C-leucine [(14)C-Leu] incorporation was used to analyze protein synthesis at PN1, and Western Blot method was used to analyze protein levels of Bax, Bcl-2 and Poly(ADP-ribose) polymerase-1 (PARP-1) in the hippocampus (PN3-PN21). During the first 22 days of postnatal life, body weight gain, length, skull measures, tooth eruption, eye opening and righting reflex have been assessed. Pups from naive mothers were used as controls. Experimental pups showed a compensated metabolic acidosis and hyperglycemia. At PN1, the [(14)C-Leu] incorporation into different studied areas of experimental pups was lower than in the control pups. During development, the protein levels of Bax, Bcl-2 and PARP-1 in the hippocampus of experimental pups were altered when compared with control pups. A decreased level of pro- and anti-apoptotic proteins was verified in the early postnatal age (PN3), and an increased level of pro-apoptotic proteins concomitant with a reduced level of anti-apoptotic protein was observed at the later stages of the development (PN21). Experimental pups had a delay in postnatal growth and development beyond disturb in protein synthesis and some protein expression during development. These changes can be result from hormonal alterations linked to stress and/or hypoxic events caused by maternal epileptic seizures during pregnancy. PMID:27085526

  18. Binge drinking differentially affects adolescent male and female brain morphometry

    PubMed Central

    Squeglia, Lindsay M.; Sorg, Scott F.; Schweinsburg, Alecia Dager; Wetherill, Reagan R.; Pulido, Carmen; Tapert, Susan F.

    2012-01-01

    Rationale Adolescent binge drinking is concerning, as important neurodevelopments occur during this stage. Previous research suggests that binge drinking may disrupt typical brain development, and females may be particularly vulnerable. Objectives We used magnetic resonance imaging (MRI) to examine cortical thickness in adolescent females and males with and without histories of binge drinking. Methods Participants (N=59) were 16–19-year-old adolescents recruited from local schools. Recent binge drinkers (n=29, 48% female) were matched to non-drinkers (n=30, 50% female) on age, gender, pubertal development, and familial alcoholism. Participants completed a neuropsychological battery and MRI session. Cortical surfaces were reconstructed with FreeSurfer. Results Binge × gender interactions (p<.05) were seen for cortical thickness in four left frontal regions: frontal pole, pars orbitalis, medial orbital frontal, and rostral anterior cingulate. For all interactions, female bingers had thicker cortices than female controls, while male bingers had thinner cortices than male controls. Thicker left frontal cortices corresponded with poorer visuospatial, inhibition, and attention performances for female bingers (r=−0.69 to 0.50, p<0.05) and worse attention for male bingers (r=−0.69, p=0.005). Conclusions Adolescent females with recent binge drinking showed ~8% thicker cortices in left frontal regions than demographically similar female non-drinkers, which was linked to worse visuospatial, inhibition, and attention performances. In contrast, adolescent binge-drinking males showed ~7% thinner cortices in these areas than non-drinking males. These cross-sectional data suggest either different gray matter risk factors for males as for females toward developing heavy drinking, or differential adverse sequelae. PMID:21952669

  19. 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

  20. 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. PMID:21307006

  1. 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.

  2. 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

  3. 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

  4. 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

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

    PubMed

    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 carboxylase

  6. New insights into brain BDNF function in normal aging and Alzheimer disease.

    PubMed

    Tapia-Arancibia, Lucia; Aliaga, Esteban; Silhol, Michelle; Arancibia, Sandor

    2008-11-01

    The decline observed during aging involves multiple factors that influence several systems. It is the case for learning and memory processes which are severely reduced with aging. It is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging.

  7. Assessment of cognitive asymmetries in brain-damaged and normal subjects: validation of a test battery.

    PubMed Central

    Bentin, S; Gordon, H W

    1979-01-01

    A test battery designed to assess cognitive functions normally related to the left and right cerebral hemispheres was validated on 30 patients with unilateral (16 right, 14 left) lesions. The tests were preselected to reflect typical functioning of the hemispheres according to general agreement in the literature. A Cognitive Laterality Quotient (CLQ) was calculated from the difference in performance between the "right" and "left" test batteries and, therefore, reflected the relative functioning attributed to the right and left hemispheres. Using the CLQ measurement and a control group of 30 non-neurological patients matched for age and education, 28 out of 30 brain-damaged patients (93%) were categorised correctly according to side of lesion; the other two were considered to have either abnormal lateralisation (one was left handed) or asymmetrical premorbid cognitive profiles. Using only one (paired) test whose two subparts were designed to vary only slightly in task requirements to measure either right or left functioning, 29 out of 30 patients were correctly categorised. It is suggested that the concept of relative assessment of basic cognitive functions is more fruitful than general assessment of intellectual functions for use in diagnosis and rehabilitation of neurological patients or normal subjects with developmental or acquired behavioural cognitive abnormalities. Images PMID:490177

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

    PubMed Central

    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. PMID:24795562

  9. 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

  10. Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment

    PubMed Central

    Irimajiri, Rie; Michalewski, Henry J; Golob, Edward J; Starr, Arnold

    2007-01-01

    Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that has a high likelihood of progressing to Alzheimer’s disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls. When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single domain MCI and is sensitive to modulation by ChEIs. PMID:17320833

  11. Disentangling the brain networks supporting affective speech comprehension.

    PubMed

    Hervé, Pierre-Yves; Razafimandimby, Annick; Vigneau, Mathieu; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

    2012-07-16

    Areas involved in social cognition, such as the medial prefrontal cortex (mPFC) and the left temporo-parietal junction (TPJ) appear to be active during the classification of sentences according to emotional criteria (happy, angry or sad, [Beaucousin et al., 2007]). These two regions are frequently co-activated in studies about theory of mind (ToM). To confirm that these regions constitute a coherent network during affective speech comprehension, new event-related functional magnetic resonance imaging data were acquired, using the emotional and grammatical-person sentence classification tasks on a larger sample of 51 participants. The comparison of the emotional and grammatical tasks confirmed the previous findings. Functional connectivity analyses established a clear demarcation between a "Medial" network, including the mPFC and TPJ regions, and a bilateral "Language" network, which gathered inferior frontal and temporal areas. These findings suggest that emotional speech comprehension results from interactions between language, ToM and emotion processing networks. The language network, active during both tasks, would be involved in the extraction of lexical and prosodic emotional cues, while the medial network, active only during the emotional task, would drive the making of inferences about the sentences' emotional content, based on their meanings. The left and right amygdalae displayed a stronger response during the emotional condition, but were seldom correlated with the other regions, and thus formed a third entity. Finally, distinct regions belonging to the Language and Medial networks were found in the left angular gyrus, where these two systems could interface.

  12. 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.

  13. Brain size affects the behavioural response to predators in female guppies (Poecilia reticulata)

    PubMed Central

    van der Bijl, Wouter; Thyselius, Malin; Kotrschal, Alexander; Kolm, Niclas

    2015-01-01

    Large brains are thought to result from selection for cognitive benefits, but how enhanced cognition leads to increased fitness remains poorly understood. One explanation is that increased cognitive ability results in improved monitoring and assessment of predator threats. Here, we use male and female guppies (Poecilia reticulata), artificially selected for large and small brain size, to provide an experimental evaluation of this hypothesis. We examined their behavioural response as singletons, pairs or shoals of four towards a model predator. Large-brained females, but not males, spent less time performing predator inspections, an inherently risky behaviour. Video analysis revealed that large-brained females were further away from the model predator when in pairs but that they habituated quickly towards the model when in shoals of four. Males stayed further away from the predator model than females but again we found no brain size effect in males. We conclude that differences in brain size affect the female predator response. Large-brained females might be able to assess risk better or need less sensory information to reach an accurate conclusion. Our results provide experimental support for the general idea that predation pressure is likely to be important for the evolution of brain size in prey species. PMID:26203003

  14. Brain size affects the behavioural response to predators in female guppies (Poecilia reticulata).

    PubMed

    van der Bijl, Wouter; Thyselius, Malin; Kotrschal, Alexander; Kolm, Niclas

    2015-08-01

    Large brains are thought to result from selection for cognitive benefits, but how enhanced cognition leads to increased fitness remains poorly understood. One explanation is that increased cognitive ability results in improved monitoring and assessment of predator threats. Here, we use male and female guppies (Poecilia reticulata), artificially selected for large and small brain size, to provide an experimental evaluation of this hypothesis. We examined their behavioural response as singletons, pairs or shoals of four towards a model predator. Large-brained females, but not males, spent less time performing predator inspections, an inherently risky behaviour. Video analysis revealed that large-brained females were further away from the model predator when in pairs but that they habituated quickly towards the model when in shoals of four. Males stayed further away from the predator model than females but again we found no brain size effect in males. We conclude that differences in brain size affect the female predator response. Large-brained females might be able to assess risk better or need less sensory information to reach an accurate conclusion. Our results provide experimental support for the general idea that predation pressure is likely to be important for the evolution of brain size in prey species.

  15. Brain size affects the behavioural response to predators in female guppies (Poecilia reticulata).

    PubMed

    van der Bijl, Wouter; Thyselius, Malin; Kotrschal, Alexander; Kolm, Niclas

    2015-08-01

    Large brains are thought to result from selection for cognitive benefits, but how enhanced cognition leads to increased fitness remains poorly understood. One explanation is that increased cognitive ability results in improved monitoring and assessment of predator threats. Here, we use male and female guppies (Poecilia reticulata), artificially selected for large and small brain size, to provide an experimental evaluation of this hypothesis. We examined their behavioural response as singletons, pairs or shoals of four towards a model predator. Large-brained females, but not males, spent less time performing predator inspections, an inherently risky behaviour. Video analysis revealed that large-brained females were further away from the model predator when in pairs but that they habituated quickly towards the model when in shoals of four. Males stayed further away from the predator model than females but again we found no brain size effect in males. We conclude that differences in brain size affect the female predator response. Large-brained females might be able to assess risk better or need less sensory information to reach an accurate conclusion. Our results provide experimental support for the general idea that predation pressure is likely to be important for the evolution of brain size in prey species. PMID:26203003

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

    PubMed Central

    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.

    2015-01-01

    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 m2s−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. PMID:25457555

  17. Brain Activity, Personality Traits and Affect: Electrocortical Activity in Reaction to Affective Film Stimuli

    NASA Astrophysics Data System (ADS)

    Makvand Hosseini, Sh.; Azad Fallah, P.; Rasoolzadeh Tabatabaei, S. K.; Ghannadyan Ladani, S. H.; Heise, C.

    We studied the patterns of activation over the cerebral cortex in reaction to affective film stimuli in four groups of extroverts, introverts, neurotics and emotionally stables. Measures of extraversion and neuroticism were collected and resting EEG was recorded from 40 right handed undergraduate female students (19-23) on one occasion for five 30s periods in baseline condition and in affective states. Mean log-transformed absolute alpha power was extracted from 12 electrode sites and analyzed. Patterns of activation were different in personality groups. Different patterns of asymmetries were observed in personality groups in reaction to affective stimuli. Results were partly consistent with approach and withdrawal model and provided supportive evidence for the role of right frontal asymmetry in negative affects in two groups (introverts and emotionally stables) as well as the role of right central asymmetry (increase on right and decrease on left) in active affective states (anxiety and happiness) in all personality groups. Results were also emphasized on the role of decrease activity relative to baseline in cortical regions (bilaterally in frontal and unilaterally in left parietal and temporal regions) in moderating of positive and negative emotion.

  18. In vivo administration of fluorescent dextrans for the specific and sensitive localization of brain vascular pericytes and their characterization in normal and neurotoxin exposed brains.

    PubMed

    Sarkar, Sumit; Schmued, Larry

    2012-06-01

    We have aimed to develop novel histochemical markers for the labeling of brain pericytes and characterize their morphology in the normal and the excitotoxin-exposed brain, as this class of cells has received little attention until recently. Pericyte labeling was accomplished by the intracerebroventricular injection of certain fluorescent dextran conjugates, such as Fluoro-Gold-dextran, FR-dextran, FITC-dextran and Fluoro-Turquoise (FT)-dextran. 1-7 days after the tracer injection, extensive labeling of vascular pericytes was seen throughout the entire brain. These cells were found distal to the endothelial cells and exhibited large dye containing vacuoles. The morphology of the pericytes was somewhat variable, exhibiting round or amoeboid shapes within larger intracellular vesicles, while those wrapping around capillaries exhibited a more elongated appearance with finger-like projections. The use of FG-dextran resulted in bluish yellow fluorescently labeled pericytes, while FR-dextran resulted in red fluorescent labeled pericytes, FITC-dextran exhibited green fluorescent pericytes and FT-dextran showed fluorescent blue pericytes in the brain. We have used these tracers to study possible changes in morphology and pericyte number following kainic acid insult, observing that the number of pericytes in the injured or lesioned areas of the brain is dramatically reduced compared to the non-injured areas. These novel fluorochromes should be of use for studies involving the detection and localization of pericytes in both normal and pathological brain tissues.

  19. In vivo administration of fluorescent dextrans for the specific and sensitive localization of brain vascular pericytes and their characterization in normal and neurotoxin exposed brains.

    PubMed

    Sarkar, Sumit; Schmued, Larry

    2012-06-01

    We have aimed to develop novel histochemical markers for the labeling of brain pericytes and characterize their morphology in the normal and the excitotoxin-exposed brain, as this class of cells has received little attention until recently. Pericyte labeling was accomplished by the intracerebroventricular injection of certain fluorescent dextran conjugates, such as Fluoro-Gold-dextran, FR-dextran, FITC-dextran and Fluoro-Turquoise (FT)-dextran. 1-7 days after the tracer injection, extensive labeling of vascular pericytes was seen throughout the entire brain. These cells were found distal to the endothelial cells and exhibited large dye containing vacuoles. The morphology of the pericytes was somewhat variable, exhibiting round or amoeboid shapes within larger intracellular vesicles, while those wrapping around capillaries exhibited a more elongated appearance with finger-like projections. The use of FG-dextran resulted in bluish yellow fluorescently labeled pericytes, while FR-dextran resulted in red fluorescent labeled pericytes, FITC-dextran exhibited green fluorescent pericytes and FT-dextran showed fluorescent blue pericytes in the brain. We have used these tracers to study possible changes in morphology and pericyte number following kainic acid insult, observing that the number of pericytes in the injured or lesioned areas of the brain is dramatically reduced compared to the non-injured areas. These novel fluorochromes should be of use for studies involving the detection and localization of pericytes in both normal and pathological brain tissues. PMID:22525936

  20. PCNA immunoreactivity revealing normal proliferative activity in the brain of an adult Elasmobranch, Torpedo marmorata.

    PubMed

    Margotta, Vito

    2007-01-01

    The brain of adult heterothermic vertebrates can be already provided of quiescent cells, scattered ("matrix cells") and/or clustered ("matrix areas"). These typical cells, in some regions located at or near ventricular surfaces and at peri-ependymal layers, in other territories populating their framework, maintain some embryonic properties and are responsible of normal or variously experimentally induced proliferative activities. On these topics there are a great number of reports concerning Teleostean Osteichthyes, Urodele and Anuran Amphibians, Lacertilian Reptiles. At the contrary, only few are the contributions regarding the Petromyzontidae. Involving an immunocytochemical marker, the Proliferating Cell Nuclear Antigen (PCNA), revealing proliferative events, in the last years we have undertaken a reappraisal focused on these encephalic performances in normal adult poikilothermal vertebrates. To provide a valid comparison between our results and the literature data, our choice of the specimens was based on the desire to employ organisms belonging to the same or phylogenetically close species used by previous Authors in similar studies. In our immunocytochemical panorama there is a substantial agreement between our contributions and bibliographic references concerning natural encephalic proliferative phenomena in these vertebrates. At this point of our study, the last missing piece was represented by the Chondrichthyes about which the literature data are lacking. In order to fill this gap, the aim of the present research is to investigate, involving the same PCNA test, whether proliferative events also persist in the brain of adult cartilaginous fishes. The immunostaining images obtained in the Elasmo branch Torpedo marmorata, well-known for the emission of high electrical discharges, exhibit undifferentiated cells in relationship with the ependymal epithelium lining the cavities of all cerebral districts; some other neuroblasts are scattered in the mesencephalic

  1. 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.

  2. Effects of normal aging on event-related potentials and oscillatory brain activity during a haptic repetition priming task.

    PubMed

    Sebastián, Manuel; Ballesteros, Soledad

    2012-03-01

    This study reports neural repetition effects in young and older adults while performing a haptic repetition priming task consisting in the detection of the bilateral symmetry of familiar objects. To examine changes in event-related potentials (ERPs) and induced brain oscillations of object repetition priming with aging, we recorded EEGs of healthy groups of young (n=14; mean age=29.93 years) and older adults (n=15; mean age=66.4). Both groups exhibited similar behavioral haptic priming across repetitions, although young adults responded faster than the older group. Young and older adults showed ERP repetition enhancement at the 500-900 ms time window. In contrast, only the young participants showed ERP repetition suppression at the 1200-1500 ms segment. The results from the induced oscillations showed more positive amplitudes in young than in older adults at theta, alpha and beta frequencies (4-30 Hz). In addition, we found amplitude modulation related to stimulus repetition in the upper alpha and low beta sub-bands only in young adults (1250-1750 ms).The results suggest that although behavioral priming is spared with age, normal aging affects ERPs and oscillatory responses when performing an incidental priming symmetry detection task with haptically explored objects. PMID:22155374

  3. 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…

  4. 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

  5. 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…

  6. Cognitive, Affective, and Conative Theory of Mind (ToM) in Children with Traumatic Brain Injury

    PubMed Central

    Dennis, Maureen; Simic, Nevena; Bigler, Erin D.; Abildskov, Tracy; Agostino, Alba; Taylor, H. Gerry; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A.; Stancin, Terry; Yeates, Keith Owen

    2012-01-01

    We studied three forms of dyadic communication involving theory of mind (ToM) in 82 children with traumatic brain injury (TBI) and 61 children with orthopedic injury (OI): Cognitive (concerned with false belief), Affective (concerned with expressing socially deceptive facial expressions), and Conative (concerned with influencing another’s thoughts or feelings). We analyzed the pattern of brain lesions in the TBI group and conducted voxel-based morphometry for all participants in five large-scale functional brain networks, and related lesion and volumetric data to ToM outcomes. Children with TBI exhibited difficulty with Cognitive, Affective, and Conative ToM. The perturbation threshold for Cognitive ToM is higher than that for Affective and Conative ToM, in that Severe TBI disturbs Cognitive ToM but even Mild-Moderate TBI disrupt Affective and Conative ToM. Childhood TBI was associated with damage to all five large-scale brain networks. Lesions in the Mirror Neuron Empathy network predicted lower Conative ToM involving ironic criticism and empathic praise. Conative ToM was significantly and positively related to the package of Default Mode, Central Executive, and Mirror Neuron Empathy networks and, more specifically, to two hubs of the Default Mode network, the posterior cingulate/retrosplenial cortex and the hippocampal formation, including entorhinal cortex and parahippocampal cortex. PMID:23291312

  7. Discussion of Developmental Plasticity: Factors Affecting Cognitive Outcome after Pediatric Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Chapman, Sandra Bond; McKinnon, Lyn

    2000-01-01

    This article discusses psychobiological factors that affect recovery after traumatic brain injury in children and adolescents, including biological pathophysiology of the injury, the cognitive stage of the child at injury, the amount of time after injury, the challenge level of tasks, and the child's reserve of psychosocial resources. (Contains…

  8. 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.

  9. Cognitive, affective, and conative theory of mind (ToM) in children with traumatic brain injury.

    PubMed

    Dennis, Maureen; Simic, Nevena; Bigler, Erin D; Abildskov, Tracy; Agostino, Alba; Taylor, H Gerry; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen

    2013-07-01

    We studied three forms of dyadic communication involving theory of mind (ToM) in 82 children with traumatic brain injury (TBI) and 61 children with orthopedic injury (OI): Cognitive (concerned with false belief), Affective (concerned with expressing socially deceptive facial expressions), and Conative (concerned with influencing another's thoughts or feelings). We analyzed the pattern of brain lesions in the TBI group and conducted voxel-based morphometry for all participants in five large-scale functional brain networks, and related lesion and volumetric data to ToM outcomes. Children with TBI exhibited difficulty with Cognitive, Affective, and Conative ToM. The perturbation threshold for Cognitive ToM is higher than that for Affective and Conative ToM, in that Severe TBI disturbs Cognitive ToM but even Mild-Moderate TBI disrupt Affective and Conative ToM. Childhood TBI was associated with damage to all five large-scale brain networks. Lesions in the Mirror Neuron Empathy network predicted lower Conative ToM involving ironic criticism and empathic praise. Conative ToM was significantly and positively related to the package of Default Mode, Central Executive, and Mirror Neuron Empathy networks and, more specifically, to two hubs of the Default Mode Network, the posterior cingulate/retrosplenial cortex and the hippocampal formation, including entorhinal cortex and parahippocampal cortex. PMID:23291312

  10. 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…

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

    PubMed

    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.

  12. 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

  13. Affect and the Brain's Functional Organization: A Resting-State Connectivity Approach

    PubMed Central

    Rohr, Christiane S.; Okon-Singer, Hadas; Craddock, R. Cameron; Villringer, Arno; Margulies, Daniel S.

    2013-01-01

    The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a) right-lateralized dominance in emotional processing, (b) hemispheric dominance according to positive or negative valence, (c) one network for all emotional processing and (d) region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS) from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes. PMID:23935850

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

    PubMed

    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

  15. 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

  16. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

    PubMed

    Löwe, Luise Christine; 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

  17. [Can fruits and vegetables be used as substitute phantoms for normal human brain tissues in magnetic resonance imaging?].

    PubMed

    Teramoto, Daisuke; Ushioda, Yuichi; Sasaki, Ayaka; Sakurai, Yuki; Nagahama, Hiroshi; Nakamura, Manami; Sugimori, Hiroyuki; Sakata, Motomichi

    2013-10-01

    Various custom-made phantoms designed to optimize magnetic resonance imaging (MRI) sequences have been created and subsequently reported in JSRT. However, custom-made phantoms that correctly match the T1-value and T2-values of human brain tissue (gray matter and white matter) cannot be made easily or quickly. The aim of this project was to search for alternative materials, such as fruits and vegetables, for optimizing MRI sequences. The following eight fruits and vegetables were investigated: apple, tomato, melon, apple mango (Mangifera indica), banana, avocado, peach, and eggplant. Their potential was studied for use in modeling phantoms of normal human brain tissues. MRI (T1- and T2-weighted sequences) was performed on the human brain and the fruits and vegetables using various concentrations of contrast medium (gadolinium) in the same size tubes as the custom-made phantom. The authors compared the signal intensity (SI) in human brain tissue (gray matter and white matter) with that of the fruits and the custom-made phantom. The T1 and T2 values were measured for banana tissue and compared with those for human brain tissue in the literature. Our results indicated that banana tissue is similar to human brain tissue (both gray matter and white matter). Banana tissue can thus be employed as an alternative phantom for the human brain for the purpose of MRI.

  18. 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

  19. 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.

  20. 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.

  1. Non-Gaussian Diffusion Imaging for Enhanced Contrast of Brain Tissue Affected by Ischemic Stroke

    PubMed Central

    Geffroy, Françoise; Le Bihan, Denis; Shah, N. Jon

    2014-01-01

    Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC) considered so far as the “gold standard”. The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF), the stretched exponential model (SEM), and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes. PMID:24586610

  2. Gaze fixations predict brain activation during the voluntary regulation of picture-induced negative affect.

    PubMed

    van Reekum, Carien M; Johnstone, Tom; Urry, Heather L; Thurow, Marchell E; Schaefer, Hillary S; Alexander, Andrew L; Davidson, Richard J

    2007-07-01

    Recent studies have identified a distributed network of brain regions thought to support cognitive reappraisal processes underlying emotion regulation in response to affective images, including parieto-temporal regions and lateral/medial regions of prefrontal cortex (PFC). A number of these commonly activated regions are also known to underlie visuospatial attention and oculomotor control, which raises the possibility that people use attentional redeployment rather than, or in addition to, reappraisal as a strategy to regulate emotion. We predicted that a significant portion of the observed variance in brain activation during emotion regulation tasks would be associated with differences in how participants visually scan the images while regulating their emotions. We recorded brain activation using fMRI and quantified patterns of gaze fixation while participants increased or decreased their affective response to a set of affective images. fMRI results replicated previous findings on emotion regulation with regulation differences reflected in regions of PFC and the amygdala. In addition, our gaze fixation data revealed that when regulating, individuals changed their gaze patterns relative to a control condition. Furthermore, this variation in gaze fixation accounted for substantial amounts of variance in brain activation. These data point to the importance of controlling for gaze fixation in studies of emotion regulation that use visual stimuli.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Sex differences in how stress affects brain activity during face viewing.

    PubMed

    Mather, Mara; Lighthall, Nichole R; Nga, Lin; Gorlick, Marissa A

    2010-10-01

    Under stress, men tend to withdraw socially whereas women seek social support. This functional magnetic resonance imaging study indicates that stress also affects brain activity while viewing emotional faces differently for men and women. Fusiform face area response to faces was diminished by acute stress in men but increased by stress in women. Furthermore, among stressed men viewing angry faces, brain regions involved in interpreting and understanding others' emotions (the insula, temporal pole, and inferior frontal gyrus) showed reduced coordination with the fusiform face area and the amygdala, whereas the functional connectivity among these regions increased with stress for women. These findings suggest that stress influences emotional perception differently for men and women.

  8. 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

  9. Studies of a nuclear matrix protein restricted to normal brain cells and lead-induced intranuclear inclusion bodies of kidney

    SciTech Connect

    Shelton, K.; Egle, P.; Redford, K.; Bigbee, J.

    1986-05-01

    A nuclear matrix protein, p32/6.3, with an unusual tissue distribution, has been identified. Protein from 21 tissues was surveyed by immunoprobing Western blots. In normal adult rats p32/6.3 is found only in grey matter from the cerebrum and the cerebellum, occurring in both neurons and astrocytes. Other brain cell types have not been examined. The protein appears to be developmentally regulated. It is detectable in the brain within a few days after birth and reaches adult levels within one to two weeks. Brain p32/6.3 has been found in all animals tested including rat, mouse, dog, cow, pig, chicken and human. This conservation indicates a fundamental role for p32/6.3 in the nucleus of brain cells. Possible functions for p32/6.3 may be indicated by a second novel occurrence. Chronic lead poisoning characteristically induces intranuclear inclusion bodies in the cells lining kidney proximal tubules. p32/6.3 is a major constituent of these inclusion bodies. They are also rich in lead and other metals including calcium, iron, zinc, copper and cadmium. These diverse observations suggest that p32/6.3 may have a role in metal homeostasis in the brain of normal animals.

  10. 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.

  11. 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.

  12. CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood

    PubMed Central

    Kim, Woong-Ki; Alvarez, Xavier; Fisher, Jeanne; Bronfin, Benjamin; Westmoreland, Susan; McLaurin, JoAnne; Williams, Kenneth

    2006-01-01

    Perivascular macrophages are uniquely situated at the intersection between the nervous and immune systems. Although combined myeloid marker detection differentiates perivascular from resident brain macrophages (parenchymal microglia), no single marker distinguishes perivascular macrophages in humans and mice. Here, we present the macrophage scavenger receptor CD163 as a marker for perivascular macrophages in humans, monkeys, and mice. CD163 was primarily confined to perivascular macrophages and populations of meningeal and choroid plexus macrophages in normal brains and in brains of humans and monkeys with human immunodeficiency virus or simian immunodeficiency virus (SIV) encephalitis. Scattered microglia in SIV encephalitis lesions and multinucleated giant cells were also CD163 positive. Consistent with prior findings that perivascular macrophages are primary targets of human immunodeficiency virus and SIV, all SIV-infected cells in the brain were CD163 positive. Using fluorescent dyes that definitively and selectively label perivascular macrophages in vivo, we confirmed that dye-labeled simian perivascular macrophages were CD163 positive and able to repopulate the central nervous system within 24 hours. Flow cytometric studies demonstrated a subset of monocytes (CD163+CD14+CD16+) that were immunophenotypically similar to brain perivascular macrophages. These findings recognize CD163+ blood monocytes/macrophages as a source of brain perivascular macrophages and underscore the utility of this molecule in studying the biology of perivascular macrophages and their precursors in humans, monkeys, and mice. PMID:16507898

  13. 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…

  14. 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…

  15. Low spatial frequency filtering modulates early brain processing of affective complex pictures.

    PubMed

    Alorda, Catalina; Serrano-Pedraza, Ignacio; Campos-Bueno, J Javier; Sierra-Vázquez, Vicente; Montoya, Pedro

    2007-11-01

    Recent research on affective processing has suggested that low spatial frequency information of fearful faces provide rapid emotional cues to the amygdala, whereas high spatial frequencies convey fine-grained information to the fusiform gyrus, regardless of emotional expression. In the present experiment, we examined the effects of low (LSF, <15 cycles/image width) and high spatial frequency filtering (HSF, >25 cycles/image width) on brain processing of complex pictures depicting pleasant, unpleasant, and neutral scenes. Event-related potentials (ERP), percentage of recognized stimuli and response times were recorded in 19 healthy volunteers. Behavioral results indicated faster reaction times in response to unpleasant LSF than to unpleasant HSF pictures. Unpleasant LSF pictures and pleasant unfiltered pictures also elicited significant enhancements of P1 amplitudes at occipital electrodes as compared to neutral LSF and unfiltered pictures, respectively; whereas no significant effects of affective modulation were found for HSF pictures. Moreover, mean ERP amplitudes in the time between 200 and 500ms post-stimulus were significantly greater for affective (pleasant and unpleasant) than for neutral unfiltered pictures; whereas no significant affective modulation was found for HSF or LSF pictures at those latencies. The fact that affective LSF pictures elicited an enhancement of brain responses at early, but not at later latencies, suggests the existence of a rapid and preattentive neural mechanism for the processing of motivationally relevant stimuli, which could be driven by LSF cues. Our findings confirm thus previous results showing differences on brain processing of affective LSF and HSF faces, and extend these results to more complex and social affective pictures.

  16. 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

  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. Technetium-99m ECD: a new brain imaging agent: in vivo kinetics and biodistribution studies in normal human subjects.

    PubMed

    Vallabhajosula, S; Zimmerman, R E; Picard, M; Stritzke, P; Mena, I; Hellman, R S; Tikofsky, R S; Stabin, M G; Morgan, R A; Goldsmith, S J

    1989-05-01

    Lipophilic neutral 99mTc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, 99mTc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of [99mTc]ECD showed that the maximum 99mTc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of 99mTc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of [99mTc]ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of [99mTc]ECD. These results show that [99mTc]ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.

  19. Technetium-99m ECD: a new brain imaging agent: in vivo kinetics and biodistribution studies in normal human subjects

    SciTech Connect

    Vallabhajosula, S.; Zimmerman, R.E.; Picard, M.; Stritzke, P.; Mena, I.; Hellman, R.S.; Tikofsky, R.S.; Stabin, M.G.; Morgan, R.A.; Goldsmith, S.J.

    1989-05-01

    Lipophilic neutral /sup 99m/Tc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, /sup 99m/Tc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of (/sup 99m/Tc)ECD showed that the maximum /sup 99m/Tc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of /sup 99m/Tc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of (/sup 99m/Tc)ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of (/sup 99m/Tc)ECD. These results show that (/sup 99m/Tc)ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.

  20. Total and Regional Brain Volumes in a Population-Based Normative Sample from 4 to 18 Years: The NIH MRI Study of Normal Brain Development

    PubMed Central

    2012-01-01

    Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5–18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents. PMID:21613470

  1. Acute stress differentially affects aromatase activity in specific brain nuclei of adult male and female quail.

    PubMed

    Dickens, Molly J; Cornil, Charlotte A; Balthazart, Jacques

    2011-11-01

    The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress-induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15 min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction.

  2. 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.

  3. 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

  4. Oxygen at 2 atmospheres absolute pressure does not increase the radiation sensitivity of normal brain in rats

    SciTech Connect

    Routh, A.; Kapp, J.P.; Smith, E.E.; Bebin, J.; Barnes, T.; Hickman, B.T.

    1984-07-01

    Cranial radiation was administered to CD Fisher rats at 1.0, 1.5 and 2.0 atmospheres oxygen pressure. Life span following radiation was recorded. Surviving animals were killed at 28 weeks and the brains were examined independently by two neuropathologists. Survival time was significantly less in animals receiving higher doses of radiation but showed no relationship to the oxygen pressure in the environment of the animal at the time radiation was administered. Microscopic examination of the brain did not reveal any differences in animals radiated in a normobaric or hyperbaric oxygen environment. It is concluded that hyperbaric oxygen does not sensitize the normal brain to the effects of ionizing radiation.

  5. 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.

  6. In vitro study on the alterations of brain tubulin structure and assembly affected by magnetite nanoparticles.

    PubMed

    Dadras, Ali; Riazi, Gholam Hossein; Afrasiabi, Ali; Naghshineh, Ali; Ghalandari, Behafarid; Mokhtari, Farzad

    2013-03-01

    In recent decades, considerable efforts have been made to understand the mechanism of memory, cognition, and relevant neurodegenerative diseases in the human brain. Several studies have shown the importance of microtubule proteins in the memory mechanism and memory dysfunction. Microtubules possess dynamicity, which is essential for functions of neuronal networks. Microtubule-associated proteins, i.e., tau, play vital roles in microtubule stability. On the other hand, the ferromagnetic mineral magnetite (Fe(3)O(4)) has been detected in the normal human brain, and elevated levels of magnetite are also observed in the brains of Alzheimer's disease patients. Therefore, we propose that a relationship between microtubule organization in axons and brain magnetite nanoparticles is possible. In this study we found alterations of microtubule polymerization in the presence of increasing concentrations of magnetite through transmission electron microscopy images and a turbidimetry method. Structural changes of microtubule and tau protein, as an essential microtubule-associated protein for tubulin assembly, were detected via circular dichroism spectroscopy, intrinsic fluorescence, and 8-anilino-1-naphthalenesulfonic acid fluorometry. We predicted three possible binding sites on tau protein and one possible binding site on tubulin dimer for magnetite nanoparticles. Magnetite also causes the morphology of PC12 cells to change abnormally and cell viability to decrease. Finally, we suggest that magnetite changes microtubule dynamics and polymerization through two paths: (1) changing the secondary and tertiary structure of tubulin and (2) binding to either tubulin dimer or tau protein and preventing tau-tubulin interaction.

  7. 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

  8. Anabolic androgenic steroid affects competitive behaviour, behavioural response to ethanol and brain serotonin levels.

    PubMed

    Lindqvist, Ann-Sophie; Johansson-Steensland, Pia; Nyberg, Fred; Fahlke, Claudia

    2002-06-15

    The present study investigated whether anabolic androgenic steroid (AAS) treatment (daily subcutaneous injections during 2 weeks with nandrolone decanoate; 15 mg/kg) affects competitive behaviour, and locomotor activity response to a sedative dose of ethanol (0.5 g ethanol/kg). In addition, levels of brain monoamines were assessed. The results showed that AAS treated animals exhibited enhanced dominant behaviour in the competition test compared to controls. The AAS groups' locomotor activity was not affected by ethanol in contrast to the controls who showed a sedative locomotor activity. AAS animals had significant lower levels of serotonin in basal forebrain and dorsal striatum compared to controls. These findings further strengthen the fact that AAS affects behaviour, as well as biochemical parameters. Based on previous studies and results from the present study, we hypothesize that AAS abuse may constitute a risk factor for disinhibitory behaviour, partly by affecting the serotonergic system.

  9. Impairment in cognitive and affective empathy in patients with brain lesions: anatomical and cognitive correlates.

    PubMed

    Shamay-Tsoory, S G; Tomer, R; Goldsher, D; Berger, B D; Aharon-Peretz, J

    2004-11-01

    The present study was designed to examine the degree of impairment in cognitive and affective empathy among patients with focal brain lesions, and the contribution of specific cognitive abilities (such as cognitive flexibility and processing of emotional information), to empathy. The cognitive and affective empathic response of patients with localized prefrontal lesions (n=36) was compared to responses of patients with parietal lesions (n=15) and healthy control subjects (n=19). Results indicate that patients with prefrontal lesions (especially those with lesions involving the orbitoprefrontal and medial regions) were significantly impaired in both cognitive and affective empathy as compared to parietal patients and healthy controls. When the damage was restricted to the prefrontal cortex, either left- or right-hemisphere lesions resulted in impaired empathy. However, when the lesion involved the right hemisphere, patients with parietal lesions were also impaired. The pattern of relationships between cognitive performance and empathy suggested dissociation between the cognitive correlates of affective and cognitive empathy. PMID:15590464

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

    PubMed

    Lecrux, C; Hamel, E

    2016-10-01

    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'. PMID:27574304

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

    PubMed

    Lecrux, C; Hamel, E

    2016-10-01

    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'.

  12. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    PubMed Central

    2011-01-01

    Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age. PMID:21943199

  13. Prenatal sodium arsenite affects early development of serotonergic neurons in the fetal rat brain.

    PubMed

    Senuma, Mika; Mori, Chisato; Ogawa, Tetsuo; Kuwagata, Makiko

    2014-11-01

    Prenatal arsenite exposure has been associated with developmental disorders in children, including reduced IQ and language abnormalities. Animal experiments have also shown that exposure to arsenite during development induced developmental neurotoxicity after birth. However, the evidence is not enough, and the mechanism is poorly understood, especially on the exposure during early brain development. This study assessed effects of sodium (meta) arsenite shortly after exposure on early developing fetal rat brains. Pregnant rats were administered 50 mg/L arsenite in their drinking water or 20 mg/kg arsenite orally using a gastric tube, on gestational days (GD) 9-15. Fetal brains were examined on GD16. Pregnant rats administered 20 mg/kg arsenite showed reductions in maternal body weight gain and food consumption during treatment, but not with 50 mg/L arsenite. Arsenite did not affect fetal development, as determined by body weight, mortality and brain size. Arsenite also did not induce excessive cell death or affect neural cell division in any region of the fetal neuroepithelium. Thyrosine hydroxylase immunohistochemistry revealed no difference in the distribution of catecholaminergic neurons between fetuses of arsenite treated and control rats. However, reductions in the number of serotonin positive cells in the fetal median and dorsal raphe nuclei were observed following maternal treatment with 20mg/kg arsenite. Image analysis showed that the serotonin positive areas decreased in all fetal mid- and hind-brain areas without altering distribution patterns. Maternal stress induced by arsenite toxicity did not alter fetal development. These results suggest that arsenite-induced neurodevelopmental toxicity involves defects in the early development of the serotonin nervous system.

  14. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    PubMed

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  15. 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

  16. Use of ImageJ software for histomorphometric evaluation of normal and severely affected canine ear canals.

    PubMed

    Zur, Gila; Klement, Eyal

    2015-10-01

    Morphological studies comparing normal and diseased ear canals use primarily subjective scoring. The aim of this study was to compare normal and severely affected ears in dogs with objective measurements using ImageJ software. Ear canals were harvested from cadavers with normal ears and from dogs that underwent total ear canal ablation for unresolved otitis. Histopathology samples from ear canals were evaluated by semi-quantitative scoring and also by using ImageJ-software for histomorphometric measurements. The normal ears were compared to the severely affected ears using the 2 methods. The 2 methods were significantly (P < 0.0001) correlated for epidermal hyperplasia, ceruminous gland dilation, and hyperplasia and tissue inflammation, which were significantly greater in the severely affected ears (P < 0.0001). This study demonstrated that there is a very high correlation between the 2 methods for the most markedly affected components of otitis externa and that ImageJ software can be efficiently used to measure and evaluate ear canal histomorphometry.

  17. 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. PMID:24862851

  18. Effects of dopaminergic modulation on electrophysiological brain response to affective stimuli

    PubMed Central

    Nijs, Ilse; Pepplinkhuizen, Lolke

    2007-01-01

    Introduction Several theoretical accounts of the role of dopamine suggest that dopamine has an influence on the processing of affective stimuli. There is some indirect evidence for this from studies showing an association between the treatment with dopaminergic agents and self-reported affect. Materials and methods We addressed this issue directly by examining the electrophysiological correlates of affective picture processing during a single-dose treatment with a dopamine D2 agonist (bromocriptine), a dopamine D2 antagonist (haloperidol), and a placebo. We compared early and late event-related brain potentials (ERPs) that have been associated with affective processing in the three medication treatment conditions in a randomized double-blind crossover design amongst healthy males. In each treatment condition, subjects attentively watched neutral, pleasant, and unpleasant pictures while ERPs were recorded. Results Results indicate that neither bromocriptine nor haloperidol has a selective effect on electrophysiological indices of affective processing. In concordance with this, no effects of dopaminergic modulation on self-reported positive or negative affect was observed. In contrast, bromocriptine decreased overall processing of all stimulus categories regardless of their affective content. Discussion The results indicate that dopaminergic D2 receptors do not seem to play a crucial role in the selective processing of affective visual stimuli. PMID:17891382

  19. Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain

    PubMed Central

    Omata, Yo; Salvador, Gabriela A.; Oteiza, Patricia I.

    2013-01-01

    A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors. PMID:23377617

  20. Hydroxysteroid sulfotransferase 2B1b expression and localization in normal human brain

    PubMed Central

    Salman, Emily D.; Faye-Petersen, Ona; Falany, Charles N.

    2012-01-01

    Steroid sulfonation in the human brain has not been well characterized. The major sulfotransferase (SULT) isoforms that conjugate steroids in humans are SULT1E1, SULT2A1, and SULT2B1b. SULT2B1b catalyzes the sulfonation of 3β-hydroxysteroids, including neurosteroids dehydroepiandrosterone and pregnenolone, as well as cholesterol and several hydroxycholesterols. SULT2B1b mRNA and protein expression were detected in adult and fetal human brain sections, whereas neither mRNA, nor protein expression were identified for SULT1E1 or SULT2A1. Using immunohistochemical analysis, SULT2B1b expression was detected in neurons and oligodendrocytes in adult brain and in epithelial tissues in 28-week-old fetal brain. Sulfonation of cholesterol, oxysterols, and neurosteroids in the brain is apparently catalyzed by SULT2B1b since expression of neither SULT2A1 nor SULT1E1 was detected in human brain sections. SULT2B1b mRNA and protein were also detected in human U373-MG glioblastoma cells. Both mRNA and protein expression of liver X receptor (LXR)-β, but not LXR-α, were detected in U373-MG cells, and LXR-β activation resulted in a decrease in SULT2B1b protein expression. Since hydroxycholesterols are important physiological LXR activators, this suggests a role for regulation of sterol metabolism by LXR and SULT2B1b. Therefore, elucidating key enzymes in the metabolism of cholesterol and neurosteroids could help define the properties of steroid conjugation in the human brain. PMID:24683427

  1. Cell biology of normal brain aging: synaptic plasticity-cell death.

    PubMed

    Dorszewska, Jolanta

    2013-04-01

    Senescence of the brain seems to be related to increased levels of free oxygen radical (FOR). FOR may damage macromolecular compounds such as: proteins, lipids, and DNA. In the aging brain, increased FOR levels damage DNA, mitochondrial DNA (mtDNA), and nuclear DNA (nDNA). In DNA they damage single and double strands, leading to mutations in mtDNA and nDNA. Damage to mtDNA seems to result in decay of mitochondria, decreased production of ATP, and in the activation of the apoptotic process. In the aging brain, apoptosis does not seem to be activated in wild-type p53-expressing cells because the elevated levels of the p53 protein are no longer accompanied by decreased levels of the Bcl-2 protein and increased levels of the Bax protein. It seems that, in the aging brain, changes in the metabolism of neurons may lead to their decreased numbers in the cerebral and cerebellar cortex, hippocampus, basal nucleus of Meynert, locus ceruleus, and substantia nigra, as well as to decreased numbers of synapses and disturbed stimulation of synaptic plasticity in the senescent brain. Simultaneously, a decrease in neurogenesis in the aging brain may lead to a decline in the maintenance of tissue integrity, function, and regenerative response. Environmental enrichment and physical activity may improve hippocampal neurogenesis and induce neuronal plasticity. The morphological lesions in the senescent brain are undoubtedly followed by a disturbed balance between various types of neurons in the CNS. Nevertheless, the high plasticity of the CNS in humans most probably does not allow for the development of abnormalities in higher functions. PMID:23740630

  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. PMID:26920424

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

    PubMed Central

    van Harreveld, Frenk; Rotteveel, Mark; Lelieveld, Gert-Jan; Crone, Eveline A.

    2014-01-01

    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. PMID:23685774

  4. 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.

  5. 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. PMID:23685774

  6. 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...

  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. Secrets of aging: What does a normally aging brain look like?

    PubMed Central

    2011-01-01

    Over the past half century, remarkable progress has been made in understanding the biological basis of memory and how it changes over the lifespan. An important conceptual advance during this period was the realization that normative cognitive trajectories can exist independently of dementing illness. In fact, mammals as different as rats and monkeys, who do not spontaneously develop Alzheimer’s disease, show memory impairments at advanced ages in similar domains as those observed in older humans. Thus, animal models have been particularly helpful in revealing brain mechanisms responsible for the cognitive changes that occur in aging. During these past decades, a number of empirical and technical advances enabled the discoveries that began to link age-related changes in brain function to behavior. The pace of innovation continues to accelerate today, resulting in an expanded window through which the secrets of the aging brain are being deciphered. PMID:22003369

  9. Laterality of mental imagery generation and operation: tests with brain-damaged patients and normal adults.

    PubMed

    Hatta, T; Koike, M; Langman, P

    1994-08-01

    The relationships between hemispheric function and components of the imagery process were examined in patients with unilateral right and left brain damage and in intact adult subjects. In the image generation condition, subjects were required to mentally generate Katakana letters corresponding to Hiragana letters displayed on a CRT. The results for the intact adults suggested a left hemisphere superiority, but the unilaterally brain-damaged subjects showed no hemispheric difference in this task. In the imagery operation task (transformation or lateral translation), subjects were asked to find a genuine Kanji among distractors (pseudo-Kanji) that were constructed from two Kanji radicals (themselves real Kanji) that were either displayed in reverse order or shifted apart. The results for both intact adults and patients with unilateral brain damage suggest the superiority of the right hemisphere. PMID:7525640

  10. 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.

  11. Photoperiod affects distribution of dynorphin A in the brain of Siberian hamster.

    PubMed

    Meyza, Ksenia Z; Sotowska-Brochocka, Jolanta

    2006-01-01

    Dynorphin A1-77 (DYN A1-17) acting in the CNS is known to affect thermoregulation, water and energy balance in the short time scale. In this study a long-term alteration of these functions induced by changes of day length in the highly photoperiodic species, the Siberian hamster (Phodopus sungorus) was studied using immunohistochemistry for DYN A1-17. We found that in the long day (LD, L:D 16 h:8 h) more brain areas express DYN A1-17 peptide than in the short day (SD, L:D 8 h:16 h) conditions. Structures of the hypothalamo-pituitary axis as well as cells of the ependyma, subcomissural organ and choroid plexus of the lateral and third brain ventricles are immunoreactive to anti-dynorphin IgG only in the LD. This might indicate a seasonal regulatory role of DYN A1-17 in physiological adaptations to severe climate changes.

  12. The metabolism of Tay-Sachs ganglioside: catabolic studies with lysosomal enzymes from normal and Tay-Sachs brain tissue.

    PubMed

    Tallman, J F; Johnson, W G; Brady, R O

    1972-09-01

    The catabolism of Tay-Sachs ganglioside, N-acetylgalactosaminyl- (N-acetylneuraminosyl) -galactosylglucosylceramide, has been studied in lysosomal preparations from normal human brain and brain obtained at biopsy from Tay-Sachs patients. Utilizing Tay-Sachs ganglioside labeled with (14)C in the N-acetylgalactosaminyl portion or (3)H in the N-acetylneuraminosyl portion, the catabolism of Tay-Sachs ganglioside may be initiated by either the removal of the molecule of N-acetylgalactosamine or N-acetylneuraminic acid. The activity of the N-acetylgalactosamine-cleaving enzyme (hexosaminidase) is drastically diminished in such preparations from Tay-Sachs brain whereas the activity of the N-acetylneuraminic acid-cleaving enzyme (neuraminidase) is at a normal level. Total hexosaminidase activity as measured with an artificial fluorogenic substrate is increased in tissues obtained from patients with the B variant form of Tay-Sachs disease and it is virtually absent in the O-variant patients. The addition of purified neuraminidase and various purified hexosaminidases exerted only a minimal synergistic effect on the hydrolysis of Tay-Sachs ganglioside in the lysosomal preparations from the control or patient with the O variant of Tay-Sachs disease.

  13. 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.

  14. Landmark-based morphometrics of the normal adult brain using MRI.

    PubMed

    Free, S L; O'Higgins, P; Maudgil, D D; Dryden, I L; Lemieux, L; Fish, D R; Shorvon, S D

    2001-05-01

    We describe the application of statistical shape analysis to homologous landmarks on the cortical surface of the adult human brain. Statistical shape analysis has a sound theoretical basis. Landmarks are identified on the surface of a 3-D reconstruction of the segmented cortical surface from magnetic resonance image (MRI) data. Using publicly available software (morphologika) the location and size dependence of the landmarks are removed and the differences in landmark distribution across subjects are analysed using principal component analysis. These differences, representing shape differences between subjects, can be visually assessed using wireframe models and transformation grids. The MRI data of 58 adult brains (27 female and 15 left handed) were examined. Shape differences in the whole brain are described which concern the relative orientation of frontal lobe sulci. Analysis of all 116 hemispheres revealed a statistically significant difference (P < 0.001) between left and right hemispheres. This finding was significant for right- but not left-handed subjects alone. No other significant age, gender, handedness, or brain-size correlations with shape differences were found.

  15. Cellular Distribution of NDRG1 Protein in the Rat Kidney and Brain During Normal Postnatal Development

    PubMed Central

    Wakisaka, Yoshinobu; Furuta, Akiko; Masuda, Katsuaki; Morikawa, Wataru; Kuwano, Michihiko; Iwaki, Toru

    2003-01-01

    N-myc downregulated gene 1 (NDRG1) is a 43-kD protein whose mRNA is induced by DNA damage, hypoxia, or prolonged elevation of intracellular calcium. Although NDRG1 is also upregulated during cell differentiation, there are few studies on NDRG1 expression during postnatal development. Here we investigated the expression and cellular distribution of NDRG1 protein in rat kidney and brain during postnatal development. Immunohistochemical analysis revealed that the cellular localization of NDRG1 protein in the kidney changed from the proximal convoluted tubules to the collecting ducts between postnatal days 10 and 20. In the brain, a change in cellular expression was also found from the hippocampal pyramidal neurons to the astrocytes in the gray matter during the same postnatal period. These alterations in the cellular distribution of NDRG1 were associated with shifts in the molecular assembly on Western blots. Under non-reduced conditions, the main NDRG1 band was found only around 215 kD in both kidney and brain during the early postnatal stage. After postnatal day 10, the immunoreactive bands shifted to 43 kD in the kidney and 129 kD in the brain. These changes in the cellular distribution and state of assembly may correlate with the functional maturation of both organs. PMID:14566023

  16. Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters.

    PubMed

    Schneider, Adele; Bardakjian, Tanya M; Zhou, Jie; Hughes, Nkecha; Keep, Rosanne; Dorsainville, Darnelle; Kherani, Femida; Katowitz, James; Schimmenti, Lisa A; Hummel, Marybeth; Fitzpatrick, David R; Young, Terri L

    2008-11-01

    The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10-15% of individuals with bilateral anophthalmia. Extra-ocular anomalies are common. The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia/microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband.

  17. 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…

  18. 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

  19. 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

    2010-01-01

    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. PMID:21170334

  20. Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain.

    PubMed

    Shah, Disha; Blockx, Ines; Keliris, Georgios A; Kara, Firat; Jonckers, Elisabeth; Verhoye, Marleen; Van der Linden, Annemie

    2016-07-01

    Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders. PMID:26195064

  1. Zika Brain Damage May Occur in Babies with Normal-Sized Heads

    MedlinePlus

    ... in Babies With Normal-Sized Heads Study suggests microcephaly birth defect isn't always present; cases may ... on infants born with too-small heads, or microcephaly. However, a new report suggests that newborns with ...

  2. Micronized fibres affect in vitro fermentation under normal buffered and osmotic stress conditions using porcine inocula.

    PubMed

    Aumiller, T; Mosenthin, R; Rink, F; Hartung, K; Weiss, E

    2015-12-01

    In this in vitro study, the modified Hohenheim gas test was used to determine fermentation activity and bacterial composition of pig's faecal microbial inoculum, when fermenting a standard pig diet with varying levels of crude protein (CP; 20, 24 and 28% CP), and supplemented with one of three fibre sources manufactured by micronization treatment. These were wheat envelopes (MWE), pea fibre (MPF) and lupine fibre (MLF). For comparison, inulin was used. As intestinal bacteria have to cope with varying osmotic conditions in their ecosystem, fermentation was performed under normal buffered and osmotic stress conditions. After 24 h of fermentation, total gas production and ammonia production were measured. In addition, the effect of MWE and inulin on short-chain fatty acid (SCFA) production and numbers of total eubacteria, Lactobacillus spp., Bifidobacterium spp., Enterobacteriaceae, Enterococcus spp., Clostridium cluster XIVa and Clostridium cluster IV, were determined using quantitative real-time PCR. Under normal buffered conditions, supplementation of MWE resulted in increased (p < 0.05) SCFA, acetic, propionic and valerianic acid production at CP levels of 20 and 28%. There was an increase (p < 0.05) in ammonia production for the micronized supplements, and for MWE an increased (p < 0.05) branched-chain proportion was observed, possibly due to higher availability of protein for fermentation which was released during the micronization process. Osmotic stress conditions reduced (p < 0.05) total gas as well as total SCFA, acetic and propionic acid production for all treatments, while cell counts were increased (p < 0.05) for Bifidobacterium spp., Enterococcus spp. and Lactobacillus spp. Under normal buffered conditions in combination with 24 and 28% CP levels, lactobacilli were increased for MWE, compared to inulin (p < 0.05). In conclusion, micronized supplements such as MWE may beneficially modulate pigs' intestinal microbiota by increasing SCFA production in

  3. Posture and Gender Differentially Affect Heart Rate Variability of Symptomatic Mitral Valve Prolapse and Normal Adults

    PubMed Central

    Chang, Chien-Jung; Chen, Ya-Chu; Lee, Chih-Hsien; Yang, Ing-Fang; Yang, Ten-Fang

    2016-01-01

    Background Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic MVP and normal adults had not been elucidated in Taiwan. Methods A total of 118 MVP patients (7 males, 39 ± 7 years old; and 111 females, 42 ± 13 years old) and 148 healthy control (54 males, 28 ± 4 years old; and 94 females, 26 ± 6 years old) were investigated. The diagnosis of MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to record the HRV parameters for MVP and control groups in three stationary positions. Thereafter, the HRV time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform or autoregressive methods were analyzed. Results The MVP group showed a decrease in time domain parameters and obtunded postural effects on frequency domain parameters moreso than the control group. Though the parasympathetic tone was dominant in female (higher RMSSD, nHF and lower nLF vs. male), the sympathetic outflow was higher in MVP female (lower SDNN, NN50 and higher nLF vs. normal female). While the parasympathetic activity was lower in male, sympathetic outflow was dominant in MVP male (lower nHF and higher nLF vs. normal male). Conclusions Both MVP female and male subjects had elevated levels of sympathetic outflow. The obtunded postural effects on frequency domain measures testified to the autonomic dysregulation of MVP subjects. PMID:27471360

  4. Immunohistoblot analysis on whole human hemispheres from normal and Alzheimer diseased brains.

    PubMed

    Beliczai, Zsuzsa; Varszegi, Szilvia; Gulyas, Balazs; Halldin, Christer; Kasa, Peter; Gulya, Karoly

    2008-12-01

    We demonstrate the feasibility and usefulness of the histoblot immunostaining of cryosections of whole hemispheres of healthy and Alzheimer diseased (AD) human brains by localizing a neuron-specific marker, the anti-neuronal nuclei (NeuN) antigen. As expected, cortical NeuN-immunopositive regions were generally thinner and lighter in the AD brains than in the controls. The advantages of using whole hemisphere histoblots: (1) they provide a low-resolution overview/outline of the antigen distribution in a large surface area, (2) large, thick, and/or unfixed tissue sections from post-mortem samples (perhaps of inferior tissue quality) can be compared, and (3) subsequent immunohistochemistry can be performed on the tissue sections used for the histoblots. PMID:18832000

  5. Regulation of endogenous neural stem/progenitor cells for neural repair-factors that promote neurogenesis and gliogenesis in the normal and damaged brain.

    PubMed

    Christie, Kimberly J; Turnley, Ann M

    2012-01-01

    Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

  6. α-synuclein phosphorylation and truncation are normal events in the adult human brain.

    PubMed

    Muntané, G; Ferrer, I; Martinez-Vicente, M

    2012-01-01

    α-synuclein is a key protein in Lewy body diseases (LBDs) and a major component of Lewy bodies and related aberrant cytoplasmic and neuritic inclusions. Regional differences in α-synuclein have been associated with selective neuronal vulnerability to Lewy pathology. Furthermore, phosphorylation at serine 129 (Ser129) and α-synuclein truncation have been considered crucial in the pathogenesis of Lewy inclusions. The present study shows consistent reduction in α-synuclein protein expression levels in the human substantia nigra and nucleus basalis of Meynert compared with other brain regions independently of age and pathology. Phosphorylated α-synuclein at Ser129 is naturally increased in these same regions, thus inversely related with the total amount of α-synuclein. In contrast, truncated α-synuclein is naturally observed in control and diseased brains and correlating with the total amount of α-synuclein. Several truncated variants have been identified where some of these variants are truncated at the C-terminal domain, whereas others are truncated at the N-terminal domain, and all are present in cases with and without Lewy pathology. Although accumulation of truncated α-synuclein variants and phosphorylated α-synuclein occurs in Lewy bodies, α-synuclein phosphorylation and truncation can be considered constitutive in control and diseased brains.

  7. [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.

  8. 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. PMID:18094257

  9. Simulation of normal, carrier and affected controls for large-scale genotyping of cattle for factor XI deficiency.

    PubMed

    Mukhopadhyaya, P N; Jha, M; Muraleedharan, P; Gupta, R R; Rathod, R N; Mehta, H H; Khoda, V K

    2006-01-01

    An insertion mutation within exon 12 of the factor XI gene has been described in Holstein cattle. This has opened the prospect for large-scale screening of cattle using the polymerase chain reaction (PCR) technique for the rapid identification of heterozygous animals. To facilitate such a screening process, the mutant and normal alleles of factor XI gene, represented by 244- and 320-bp PCR amplified fragments, were individually cloned in Escherichia coli using a multicopy plasmid cloning vehicle to generate pFXI-N and pFXI-M, respectively. The authenticity of the inserts was confirmed by nucleotide sequencing. A nested PCR method was developed, by which PCR amplicons generated from primers with annealing sites on the recombinant plasmids and by flanking the insert were used as templates for amplification of the diagnostic products using factor XI gene-specific primers. An equimolar mixture of both PCR amplicons, originating from pFXI-N and pFXI-M, constituted the carrier control while the individual amplicons were the affected and normal controls. The controls were used as references for in-gel comparison to screen a population of 307 cattle and 259 water buffaloes; the frequency of the mutant allele was found to be 0. No DNA size standards were required in this study. The simulated control DNA samples representing normal, carrier and affected cattle have the potential to help in large-scale screening of a cattle population for individuals that are carriers or affected by factor XI deficiency.

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

    PubMed

    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

  11. 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.

  12. 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

  13. Ethanol Extract of Hedyotis diffusa Willd Affects Immune Responses in Normal Balb/c Mice In Vivo.

    PubMed

    Kuo, Yu-Jui; Lin, Jing-Pin; Hsiao, Yung-Ting; Chou, Guan-Ling; Tsai, Yu-Hsiang; Chiang, Su-Yin; Lin, Jaung-Geng; Chung, Jing-Gung

    2015-01-01

    Numerous clinical anticancer drugs are obtained from natural plants and Hedyotis diffusa Willd (EEHDW) has been used as a major component in Traditional Chinese medicine formulas since a long time. Ethanol extracts of EEHDW have been shown to possess various biological activities including anticancer function in vitro. Our earlier studies have shown that EEHDW affects immune responses in WEHI-3-generated leukemia mice, but EEHDW has not been reported to affect immune responses in a normal mouse model. Herein, we investigated whether EEHDW could affect immune responses on normal murine cells in vivo. Normal BALB/c mice were orally treated with or without EEHDW at 0, 16, 32, and 64 mg/kg or 32 mg/kg by i.p. for 3 weeks, then were weighed, and blood, liver and spleen samples were collected for further experiments. Results indicated that EEHDW did not significantly affect body and liver weight but significantly increased the spleen weight by i.p. treatment when compared to control groups. Flow cytometric assays indicated that EEHDW promoted CD11b levels at 16, 32 and 64 mg/kg oral treatment, CD19 levels at 16, 32, 64 mg/kg oral treatment and i.p. treatment, and Mac-3 levels at 16, 32 and 64 mg/kg oral treatment, however, it did not significantly affect the levels of CD3. Oral treatment with 16 and 32 mg/kg of EEHDW significantly decreased macrophage phagocytosis from PBMC; 32 mg/kg of EEHDW by i.p. treatment significantly increased phagocytosis activity of macrophages obtain from the peritoneal cavity. EEHDW at 32 mg/kg by i.p. treatment led to an increase of NK cell activities compared to oil control groups. EEHDW at 32 mg/kg of EEHDW by i.p. treatment increased B- and T-cell proliferation. Based on these observations, EEHDW seems to have promoted immune responses in this murine model. PMID:26130790

  14. 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.

  15. Progranulin Mutations Affects Brain Oscillatory Activity in Fronto-Temporal Dementia

    PubMed Central

    Moretti, Davide V.; Benussi, Luisa; Fostinelli, Silvia; Ciani, Miriam; Binetti, Giuliano; Ghidoni, Roberta

    2016-01-01

    Background: Mild cognitive impairment (MCI) is a clinical stage indicating a prodromal phase of dementia. This practical concept could be used also for fronto-temporal dementia (FTD). Progranulin (PGRN) has been recently recognized as a useful diagnostic biomarker for fronto-temporal lobe degeneration (FTLD) due to GRN null mutations. Electroencephalography (EEG) is a reliable tool in detecting brain networks changes. The working hypothesis of the present study is that EEG oscillations could detect different modifications among FTLD stages (FTD-MCI versus overt FTD) as well as differences between GRN mutation carriers versus non-carriers in patients with overt FTD. Materials and Methods: EEG in all patients and PGRN dosage in patients with a clear FTD were detected. The cognitive state has been investigated through mini mental state examination (MMSE). Results: MCI-FTD showed a significant lower spectral power in both alpha and theta oscillations as compared to overt FTD. GRN mutations carriers affected by FTLD show an increase in high alpha and decrease in theta oscillations as compared to non-carriers. Conclusion: EEG frequency rhythms are sensible to different stage of FTD and could detect changes in brain oscillatory activity affected by GRN mutations. PMID:26973510

  16. 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

  17. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    PubMed

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  18. CYCLOSPORIN A AFFECTS THE PROLIFERATION PROCESS IN NORMAL HUMAN DERMAL FIBROBLASTS.

    PubMed

    Janikowska, Grazyna; Janikowsk, Tomasz; Pyka, Alina; Wilczok, Adam; Mazurek, Urszula

    2016-01-01

    Cyclosporin A is an immunosuppressant drug that is used not only in solid transplant rejection, but also in moderate and severe forms of psoriasis, pyoderma, lupus or arthritis. Serious side effects of the drug such as skin cancer or gingival hyperplasia probably start with the latent proliferation process. Little is known about the influence of cyclosporin A on molecular signaling in epidermal tissue. Thus, the aim of this study was to estimate the influence of cyclosporin A on the process of proliferation in normal human dermal fibroblasts. Fibroblasts were cultured in a liquid growth medium in standard conditions. Cyclosporin A was added to the culture after the confluence state. Survival and proliferation tests on human dermal fibroblast cells were performed. Total RNA was extracted from fibroblasts, based on which cDNA and cRNA were synthesized. The obtained cRNA was hybridized with the expression microarray HGU-133A_2.0. Statistical analysis of 2734 mRNAs was performed by the use of GeneSpring 13.0 software and only results with p < 0.05 were accepted. Analysis of variance with Tukey post hoc test with Benjamini-Hochberg correction for all three (8, 24, 48 h) culture stages (with and without cyclosporin A) was performed to lower the number of statistically significant results from 679 to 66, and less. Between statistically and biologically significant mRNAs down-regulated were EGRJ, BUBIB, MKI67, CDK1, TTK, E2F8, TPX2, however, the INSIG1, FOSL1, HMOX1 were up-regulated. The experiment data revealed that cyclosporin A up-regulated FOSL1 in the first 24 h, afterwards down-regulating its expression. The HMOX1 gene was up-regulated in the first stage of the experiment (CsA 8 h), however, after the next 16 h of culture time its expression was down-regulated (CsA 24 h), to finally increased in the later time period. The results indicate that cyclosporin A had a significant effect on proliferation in normal human dermal fibroblasts through the changes in the

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Visual Contextual Effects of Orientation, Contrast, Flicker, and Luminance: All Are Affected by Normal Aging

    PubMed Central

    Nguyen, Bao N.; McKendrick, Allison M.

    2016-01-01

    The perception of a visual stimulus can be markedly altered by spatial interactions between the stimulus and its surround. For example, a grating stimulus appears lower in contrast when surrounded by a similar pattern of higher contrast: a phenomenon known as surround suppression of perceived contrast. Such center–surround interactions in visual perception are numerous and arise from both cortical and pre-cortical neural circuitry. For example, perceptual surround suppression of luminance and flicker are predominantly mediated pre-cortically, whereas contrast and orientation suppression have strong cortical contributions. Here, we compare the perception of older and younger observers on a battery of tasks designed to assess such visual contextual effects. For all visual dimensions tested (luminance, flicker, contrast, and orientation), on average the older adults showed greater suppression of central targets than the younger adult group. The increase in suppression was consistent in magnitude across all tasks, suggesting that normal aging produces a generalized, non-specific alteration to contextual processing in vision. PMID:27148047

  4. Normal development.

    PubMed

    Girard, Nadine; Koob, Meriam; Brunel, Herv

    2016-01-01

    Numerous events are involved in brain development, some of which are detected by neuroimaging. Major changes in brain morphology are depicted by brain imaging during the fetal period while changes in brain composition can be demonstrated in both pre- and postnatal periods. Although ultrasonography and computed tomography can show changes in brain morphology, these techniques are insensitive to myelination that is one of the most important events occurring during brain maturation. Magnetic resonance imaging (MRI) is therefore the method of choice to evaluate brain maturation. MRI also gives insight into the microstructure of brain tissue through diffusion-weighted imaging and diffusion tensor imaging. Metabolic changes are also part of brain maturation and are assessed by proton magnetic resonance spectroscopy. Understanding and knowledge of the different steps in brain development are required to be able to detect morphologic and structural changes on neuroimaging. Consequently alterations in normal development can be depicted. PMID:27430460

  5. Aging affects mechanical properties and lubricin/PRG4 gene expression in normal ligaments.

    PubMed

    Thornton, Gail M; Lemmex, Devin B; Ono, Yohei; Beach, Cara J; Reno, Carol R; Hart, David A; Lo, Ian K Y

    2015-09-18

    Age-related changes in ligament properties may have clinical implications for injuries in the mature athlete. Previous preclinical models documented mechanical and biochemical changes in ligaments with aging. The purpose of this study was to investigate the effect of aging on ligament properties (mechanical, molecular, biochemical) by comparing medial collateral ligaments (MCLs) from 1-year-old and 3-year-old rabbits. The MCLs underwent mechanical (n=7, 1-year-old; n=7, 3-year-old), molecular (n=8, 1-year-old; n=6, 3-year-old), collagen and glycosaminoglycan (GAG) content (n=8, 1-year-old; n=6, 3-year-old) and water content (n=8, 1-year-old; n=5, 3-year-old) assessments. Mechanical assessments evaluated total creep strain, failure strain, ultimate tensile strength and modulus. Molecular assessments using RT-qPCR evaluated gene expression for collagens, proteoglycans, hormone receptors, and matrix metalloproteinases and their inhibitors. While total creep strain and ultimate tensile strength were not affected by aging, failure strain was increased and modulus was decreased comparing MCLs from 3-year-old rabbits to those from 1-year-old rabbits. The mRNA expression levels for lubricin/proteoglycan 4 (PRG4) and tissue inhibitor of metalloproteinase-3 increased with aging; whereas, the mRNA expression levels for estrogen receptor and matrix metalloproteinase-1 decreased with aging. Collagen and GAG content assays and water content assessments did not demonstrate any age-related changes. The increased failure strain and decreased modulus with aging may have implications for increased susceptibility to ligament damage/injury with aging. Lubricin/PRG4 gene expression was affected by aging and its speculated role in ligament function may be related to interfascicular lubrication, which in turn may lead to altered mechanical function with aging and increases in potential for injury.

  6. Frequency Matters: Beta Band Subthalamic Nucleus Deep Brain Stimulation Induces Parkinsonian-like Blink Abnormalities in Normal Rats

    PubMed Central

    Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig

    2014-01-01

    The synchronized beta band oscillations in the basal ganglia-cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta band activity in PD motor symptoms by testing the effects of beta frequency subthalamic nucleus deep brain stimulation (STN DBS) on blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6-OHDA lesions and PD patients. These deficits were not an artifact of STN DBS because when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz DBS exaggerated blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency specific STN DBS can be used to create PD- or dystonic-like symptoms in a normal rat. PMID:25146113

  7. 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.

  8. Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology

    PubMed Central

    Gulinello, Maria; Acquarone, Mariana; Kim, John H; Spray, David C.; Barbosa, Helene S.; Sellers, Rani; Tanowitz, Herbert B.; Weiss, Louis M.

    2010-01-01

    Toxoplasma gondii is a ubiquitous intracellular parasite which chronically infects 30 to 50% of the human population. While acquired infection is primarily asymptomatic several studies have suggested that such infections may contribute to neurological and psychiatric symptoms. Previous studies in rodents have demonstated that T. gondii infection does not just kill its host, but alters the behavioral repertoire of an infected animal making it more likely that predation with occur completing the parasite life cycle. The aim of the present study was to evaluate the behavioral changes in C57BL/6 mice chronically infected with the avirulent T. gondii (ME49, a type II strain), in a comprehensive test battery. Infected mice demonstrated profound and widespread brain pathology, motor coordination and sensory deficits. In contrast, cognitive function, anxiety levels, social behavior and the motivation to explore novel objects were normal. The observed changes in behavior did not represent “gross” brain damage or dysfunction and were not due to targeted destruction of specific areas of the brain. Such changes point out the subtle interaction of this parasite with its intermediate hosts and are consistent with ideas about increased predation being an outcome of infection. PMID:20348009

  9. In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature

    SciTech Connect

    Serduc, Raphael . E-mail: rserduc@ujf-grenoble.fr; Verant, Pascale; Vial, Jean-Claude; Farion, Regine; Rocas, Linda; Remy, Chantal; Fadlallah, Taoufik M.S.; Brauer, Elke M.S.; Bravin, Alberto; Laissue, Jean; Blattmann, Hans; Sanden, Boudewijn van der

    2006-04-01

    Purpose: The purpose of this study was to assess the early effects of microbeam irradiation on the vascular permeability and volume in the parietal cortex of normal nude mice using two-photon microscopy and immunohistochemistry. Methods and Materials: The upper part of the left hemisphere of 55 mice was irradiated anteroposteriorly using 18 vertically oriented beams (width 25 {mu}m, interdistance 211 {mu}m; peak entrance doses: 312 or 1000 Gy). At different times after microbeam exposure, the microvasculature in the cortex was analyzed using intravital two-photon microscopy after intravascular injection of fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB). Changes of the vascular volume were observed at the FITC wavelength over a maximum depth of 650 {mu}m from the dura. The vascular permeability was detected as extravasations of SRB. Results: For all times (12 h to 1 month) after microbeam irradiation and for both doses, the FITC-dextran remained in the vessels. No significant change in vascular volume was observed between 12 h and 3 months after irradiation. Diffusion of SRB was observed in microbeam irradiated regions from 12 h until 12 days only after a 1000 Gy exposure. Conclusion: No radiation damage to the microvasculature was detected in normal brain tissue after a 312 Gy microbeam irradiation. This dose would be more appropriate than 1000 Gy for the treatment of brain tumors using crossfired microbeams.

  10. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  11. Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits.

    PubMed

    Ishii, Kazuhiro; Kubo, Ken-ichiro; Endo, Toshihiro; Yoshida, Keitaro; Benner, Seico; Ito, Yukiko; Aizawa, Hidenori; Aramaki, Michihiko; Yamanaka, Akihiro; Tanaka, Kohichi; Takata, Norio; Tanaka, Kenji F; Mimura, Masaru; Tohyama, Chiharu; Kakeyama, Masaki; Nakajima, Kazunori

    2015-09-01

    Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Significance statement: Recent studies reported that patients with heterotopias have a variety of clinical symptoms, such as cognitive disturbance, psychiatric symptoms, and autistic behavior. However, the causal relationship between the symptoms and heterotopias remains elusive. Here we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited behavioral deficits that have been shown to be associated with the mPFC activity in rodents. The existence of heterotopias indeed altered the neural activities of the mPFC, and

  12. Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits.

    PubMed

    Ishii, Kazuhiro; Kubo, Ken-ichiro; Endo, Toshihiro; Yoshida, Keitaro; Benner, Seico; Ito, Yukiko; Aizawa, Hidenori; Aramaki, Michihiko; Yamanaka, Akihiro; Tanaka, Kohichi; Takata, Norio; Tanaka, Kenji F; Mimura, Masaru; Tohyama, Chiharu; Kakeyama, Masaki; Nakajima, Kazunori

    2015-09-01

    Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Significance statement: Recent studies reported that patients with heterotopias have a variety of clinical symptoms, such as cognitive disturbance, psychiatric symptoms, and autistic behavior. However, the causal relationship between the symptoms and heterotopias remains elusive. Here we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited behavioral deficits that have been shown to be associated with the mPFC activity in rodents. The existence of heterotopias indeed altered the neural activities of the mPFC, and

  13. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  14. Segmenting nonenhancing brain tumors from normal tissues in magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Fletcher-Heath, Lynn M.; Hall, Lawrence O.; Goldgof, Dmitry B.

    1998-06-01

    Tumor segmentation from magnetic resonance (MR) images aids in tumor treatment by tracking the progress of tumor growth and/or shrinkage. In this paper we present an automatic segmentation method which separates non-enhancing brain tumors from healthy tissues in MR images. The MR feature images used for the segmentation consist of three weighted images (T1, T2 and proton density) for each axial slice through the head. An initial segmentation is computed using an unsupervised clustering algorithm. Then, integrated domain knowledge and image processing techniques contribute to the final tumor segmentation. The system was trained on two patient volumes and preliminary testing has shown successful tumor segmentations on four patient volumes.

  15. 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.

  16. Gas density does not affect pulmonary acoustic transmission in normal men.

    PubMed

    Mahagnah, M; Gavriely, N

    1995-03-01

    Fremitus, the transmission of sound and vibration from the mouth to the chest wall, has long been used clinically to examine the pulmonary system. Recently, modern technology has become available to measure the acoustic transfer function (TF) and transit times (TT) of the pulmonary system. Because sound speed is inversely proportional to the square root of gas density in free gas, but not in porous media, we measured the effect of air and Heliox (80% He-20% O2) breathing on pulmonary sound transmission in six healthy subjects to investigate the mechanism of sound transmission. Wide-band noise (75-2,000 Hz) was "injected" into the mouth and picked up over the trachea and chest wall. The averaged power spectra, TF, phase, and coherence were calculated using a fast Fourier transform-based algorithm. The phase data were used to calculate TT as a function of frequency. TF was found to consist of a low-pass filter property with essentially flat transmitted energy to 300 Hz and exponential decline to 600 Hz at the anterior right upper lobe (CR) and flat transmission to 100 Hz with exponential decline to 150 Hz at the right posterior base (BR). TF was not affected by breathing Heliox. The average TT values, calculated from the slopes of the averaged phase, were 1.5 +/- 0.5 ms for trachea to CR and 5.2 +/- 0.5 ms for trachea to BR transmission during air breathing. During Heliox breathing, the values of TT were 1.5 +/- 0.5 ms and 4.9 +/- 0.5 ms from the trachea to CR and from the trachea to BR locations, respectively. These results suggest that sound transmission in the respiratory system is dominated by wave propagation through the parenchymal porous structure. PMID:7775338

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

    PubMed Central

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

    2016-01-01

    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. PMID:26771139

  18. 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

  19. 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

    2008-03-01

    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.

  20. 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

  1. 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…

  2. 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.

  3. 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.

  4. MRI-based surface area estimates in the normal adult human brain: evidence for structural organisation.

    PubMed Central

    Sisodiya, S; Free, S; Fish, D; Shorvon, S

    1996-01-01

    There are a number of quantitative relationships between geometric parameters describing the structure of the normal human cerebral cortex examined in vivo using volumetric magnetic resonance imaging. A voxel-counting method is used to estimate grey-white interface surface area. The effects of bias associated with the method are considered. In 33 normal controls, the cerebral hemispheres were symmetric in terms of total volume, irrespective of handedness, but not in terms of surface areas for right-handers. The surface area of the grey matter-white matter interface was directly proportional to the cortical grey matter volume, suggesting that growth of the neocortex is primarily tangential, with repetition of a basic structural element rather than gross alterations in the thickness of the cortex. The majority of the surface area of the grey-white interface lies within gyral white matter cores. The mean thickness of the cortex of the right cerebral hemisphere in vivo was 3.0 mm and that of the left 3.3 mm. There was a relationship between the cross-sectional area of the corpus callosum and grey-white interface surface area, suggesting that a fixed proportion and cortical neurons extend interhemispheric axons. These findings suggest that there are general architectural principles governing the organisation of the complex, but ordered, human cerebral cortex. Images Fig. 1 Fig. 2 PMID:8621342

  5. 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.

  6. 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

  7. Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury.

    PubMed

    Gao, Yang; Xu, Siyi; Cui, Zhenwen; Zhang, Mingkun; Lin, Yingying; Cai, Lei; Wang, Zhugang; Luo, Xingguang; Zheng, Yan; Wang, Yong; Luo, Qizhong; Jiang, Jiyao; Neale, Joseph H; Zhong, Chunlong

    2015-07-01

    Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild-type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI-induced deficits in long-term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors. PMID:25872793

  8. 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.

  9. 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. PMID:26243271

  10. An investigation of body part as object (BPO) responses in normal and brain-damaged adults.

    PubMed

    Duffy, R J; Duffy, J R

    1989-07-01

    A test of simple pantomime was administered to three groups of adults and comparisons were made across groups of the incidence of subjects who exhibited body part as object (BPO) responses and of the mean frequency of occurrence of BPO in each group. The three groups were left-hemisphere-damaged aphasics (N = 28), right-hemisphere-damaged (N = 24), and normal controls (N = 28). The results indicated no significant differences among groups on the BPO measures. Also, to test the strength of association between the frequency of occurrence of BPO and measures of limb apraxia and severity of aphasia for the left-hemisphere-damaged aphasic group, correlation coefficients were obtained. The correlations were low and nonsignificant. The results of this investigation do not support the common clinical assumption that the occurrence of BPO during the performance of simple pantomimes is pathognomic for left-hemisphere pathology or associated with limb apraxia.

  11. 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.

  12. Cytochrome P450 differences in normal and imposex-affected female whelk Buccinum undatum from the open North Sea.

    PubMed

    Santos, M M; ten Hallers-Tjabbes, C C; Vieira, N; Boon, J P; Porte, C

    2002-01-01

    Normal and imposex-affected female Buccinum undatum were sampled from the open North Sea at three locations, one with low, and two with high shipping densities. Cytochrome P450 components and P450 aromatase activity were determined in the microsomal fractions isolated from pooled digestive gland/gonads. Cytochrome P450 aromatase activity was significantly higher (P < 0.05) in normal females collected in the low shipping density area (1,325 +/- 295 fmol/h/mg protein) than levels from imposex animals from a high shipping density area (620 +/- 287 fmol/h/mg protein). A negative correlation was found between aromatase activity and organotin body burden (r = -0.99). Levels of CYP450, cytochrome b5 and NADPH cytochrome c reductase activity did not show differences among groups. This is the first field evidence of depressed aromatase activity in imposex affected females, although additional research under laboratory controlled conditions is required to fully understand the mechanisms underlying the development of imposex in this species.

  13. 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

  14. 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

  15. Human brain EEG indices of emotions: delineating responses to affective vocalizations by measuring frontal theta event-related synchronization.

    PubMed

    Bekkedal, Marni Y V; Rossi, John; Panksepp, Jaak

    2011-10-01

    At present there is no direct brain measure of basic emotional dynamics from the human brain. EEG provides non-invasive approaches for monitoring brain electrical activity to emotional stimuli. Event-related desynchronization/synchronization (ERD/ERS) analysis, based on power shifts in specific frequency bands, has some potential as a method for differentiating responses to basic emotions as measured during brief presentations of affective stimuli. Although there appears to be fairly consistent theta ERS in frontal regions of the brain during the earliest phases of processing affective auditory stimuli, the patterns do not readily distinguish between specific emotions. To date it has not been possible to consistently differentiate brain responses to emotion-specific affective states or stimuli, and some evidence to suggests the theta ERS more likely measures general arousal processes rather than yielding veridical indices of specific emotional states. Perhaps cortical EEG patterns will never be able to be used to distinguish discrete emotional states from the surface of the brain. The implications and limitations of such approaches for understanding human emotions are discussed. PMID:21596060

  16. 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.

  17. Safety Profile of Gutless Adenovirus Vectors Delivered into the Normal Brain Parenchyma: Implications for a Glioma Phase 1 Clinical Trial

    PubMed Central

    Ghulam Muhammad, A.K.M.; Xiong, Weidong; Puntel, Mariana; Farrokhi, Catherine; Kroeger, Kurt M.; Salem, Alireza; Lacayo, Liliana; Pechnick, Robert N.; Kelson, Kyle R.; Palmer, Donna; Ng, Philip; Liu, Chunyan; Lowenstein, Pedro R.

    2012-01-01

    Abstract Adenoviral vectors (Ads) have been evaluated in clinical trials for glioma. However, systemic immunity against the vectors can hamper therapeutic efficacy. We demonstrated that combined immunostimulation and cytotoxic gene therapy provides long-term survival in preclinical glioma models. Because helper-dependent high-capacity Ads (HC-Ads) elicit sustained transgene expression, in the presence of antiadenoviral immunity, we engineered HC-Ads encoding conditional cytotoxic herpes simplex type 1 thymidine kinase and immunostimulatory cytokine Fms-like tyrosine kinase ligand-3 under the control of the TetOn system. Escalating doses of combined HC-Ads (1×108, 1×109, and 1×1010 viral particles [VP]) were delivered into the rat brain. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points after vector delivery. Histopathological analysis did not reveal any evidence of toxicity or long-term inflammation at the lower doses tested. Vector genomes were restricted to the injection site. Serum chemistry did not uncover adverse systemic side effects at any of the doses tested. Taken together, our data indicate that doses of up to 1×109 VP of each HC-Ad can be safely administered into the normal brain. This comprehensive toxicity and biodistribution study will lay the foundations for implementation of a phase 1 clinical trial for GBM using HC-Ads. PMID:22950971

  18. Are left fronto-temporal brain areas a prerequisite for normal music-syntactic processing?

    PubMed

    Sammler, Daniela; Koelsch, Stefan; Friederici, Angela D

    2011-06-01

    An increasing number of neuroimaging studies in music cognition research suggest that "language areas" are involved in the processing of musical syntax, but none of these studies clarified whether these areas are a prerequisite for normal syntax processing in music. The present electrophysiological experiment tested whether patients with lesions in Broca's area (N=6) or in the left anterior temporal lobe (N=7) exhibit deficits in the processing of structure in music compared to matched healthy controls (N=13). A chord sequence paradigm was applied, and the amplitude and scalp topography of the Early Right Anterior Negativity (ERAN) was examined, an electrophysiological marker of musical syntax processing that correlates with activity in Broca's area and its right hemisphere homotope. Left inferior frontal gyrus (IFG) (but not anterior superior temporal gyrus - aSTG) patients with lesions older than 4 years showed an ERAN with abnormal scalp distribution, and subtle behavioural deficits in detecting music-syntactic irregularities. In one IFG patient tested 7 months post-stroke, the ERAN was extinguished and the behavioural performance remained at chance level. These combined results suggest that the left IFG, known to be crucial for syntax processing in language, plays also a functional role in the processing of musical syntax. Hence, the present findings are consistent with the notion that Broca's area supports the processing of syntax in a rather domain-general way.

  19. 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.

  20. Litter Environment Affects Behavior and Brain Metabolic Activity of Adult Knockout Mice

    PubMed Central

    Crews, David; Rushworth, David; Gonzalez-Lima, Francisco; Ogawa, Sonoko

    2009-01-01

    In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s), the ratio of the various genotypes in the litter. Both Sex and Genotype ratios of the litter affect the nature and quality of the individual's behavior later in adulthood, as well as metabolic activity in brain nuclei that underlie these behaviors. Mice were raised in litters reconstituted shortly after to birth to control for sex ratio and genotype ratio (wild type pups versus pups lacking a functional estrogen receptor α). In both males and females, the Sex and Genotype of siblings in the litter affected aggressive behaviors as well as patterns of metabolic activity in limbic nuclei in the social behavior network later in adulthood. Further, this pattern in males varied depending upon the Genotype of their brothers and sisters. Principal Components Analysis revealed two components comprised of several amygdalar and hypothalamic nuclei; the VMH showed strong correlations in both clusters, suggesting its pivotal nature in the organization of two neural networks. PMID:19707539

  1. 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

  2. Sleep deprivation does not affect neuronal susceptibility to mild traumatic brain injury in the rat.

    PubMed

    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

  3. MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects.

    PubMed

    Bartzokis, G; Cummings, J L; Markham, C H; Marmarelis, P Z; Treciokas, L J; Tishler, T A; Marder, S R; Mintz, J

    1999-02-01

    Tissue iron levels in the extrapyramidal system of earlier- and later-onset Parkinson's disease (PD) subjects were evaluated in vivo using a magnetic resonance imaging (MRI) method. The method involves scanning subjects in both high- and low-field MRI instruments, measuring tissue relaxation rate (R2), and calculating the field-dependent R2 increase (FDRI) which is the difference between the R2 measured with the two MRI instruments. In tissue, only ferritin iron is known to increase R2 in a field-dependent manner and the FDRI measure is a specific measure of this tissue iron pool. Two groups of male subjects with PD and two age-matched groups of normal control males were studied. The two groups of six subjects with PD consisted of subjects with earlier- or later-onset (before or after age 60) PD. FDRI was measured in five subcortical structures: the substantia nigra reticulata (SNR), substantia nigra compacta (SNC), globus pallidus, putamen, and caudate nucleus, and in one comparison region; the frontal white matter. Earlier-onset PD subjects had significant (p < 0.05) increases in FDRI in the SNR, SNC, putamen, and globus pallidus, while later-onset PD subjects had significantly decreased FDRI in the SNR when compared to their respective age-matched controls. Controlling for illness duration or structure size did not meaningfully alter the results. Published post-mortem studies on SN iron levels indicate decreased ferritin levels and increased free iron levels in the SN of older PD subjects, consistent with the decreased FDRI observed in our later-onset PD sample, which was closely matched in age to the post-mortem PD samples. The FDRI results suggest that disregulation of iron metabolism occurs in PD and that this disregulation may differ in earlier- versus later-onset PD. PMID:10215476

  4. PCNA immunoreactivity revealing normal proliferative activity in the brain of adult Lampetra planeri (Bloch, 1784).

    PubMed

    Margotta, Vito; Caronti, Brunella; Colombari, Paolo Tito; Castiglia, Riccardo

    2007-01-01

    It is now well known that the Teleosts among Osteichthyes, Urodele and Anuran Amphibians, Lacertilian Reptiles possess encephalic natural proliferative activities even into adulthood, as demonstrated by a great number of researches performed both under normal and various experimental conditions. Few years ago we have undertaken in adult heterothermic vertebrates a reappraisal on spontaneous cerebral proliferative events involving some organisms (Podarcis sicula, Triturus carnifex, Rana esculenta, Carassius carassius) representative of these vertebrates and belonging to the same or phylogenetically similar species used by previous researchers in studies having the same object. In our investigations, these performances were revealed by a proliferative immunocytochemical marker, the Proliferating Cell Nuclear Antigen (PCNA). At this point of our study in the scenario emerging from findings a missing piece is represented by Petromyzontidae. To fill up this gap in the present investigation, using our usual test, we have paid attention to adult specimens of Lampetra planeri. The obtained immunostaining panorama has revealed the presence of a considerable number of spontaneous proliferative activities. These events might differ in quantity, in various encephalic districts. PCNA-labelled cells appeared scattered in the cranial portion of olfactory bulbs, while the PCNA expression has been observed steadily localized with a distinctly continous distribution in cells interposed among the ependymal epithelium which lines the cavities of the proximal portion of the olfactory region and of the cerebral ventricles. DNA synthesis activity has been also found in cells scattered in the telencephalic, diencephalic, mesencephalic and medulla oblongata periventricular grey. This immunoreactivity was not revealable in the cerebellum. Our findings are discussed in the light of bibliographic news.

  5. Affective responses to increasing levels of exercise intensity in normal-weight, overweight, and obese middle-aged women.

    PubMed

    Ekkekakis, Panteleimon; Lind, Erik; Vazou, Spiridoula

    2010-01-01

    At least 60 min of daily physical activity (PA) are recommended for weight control, a target achieved by only 3% of obese (OB) women. The purposes of this study were to examine (i) the affective responses of normal-weight (NW), overweight (OW), and OB middle-aged sedentary women to exercise of increasing intensity and (ii) the relationship of affective responses to self-efficacy and social physique anxiety. The women participated in a graded treadmill protocol to volitional exhaustion while providing ratings of pleasure-displeasure and perceived activation each minute. The Activation Deactivation Adjective Check List (AD ACL) was also completed before and after exercise. The affective responses of NW and OW women did not differ. However OB women gave lower pleasure ratings during the incremental protocol and reported lower Energy scores immediately after the protocol. Social physique anxiety, but not self-efficacy, was inversely related to pleasure and energy. The lower levels of pleasure and energy experienced by OB than nonobese women could account in part for their dramatically low levels of PA participation. Modifying the cognitive antecedents of social physique anxiety might be a useful intervention strategy.

  6. Functional brain interactions that serve cognitive-affective processing during pain and placebo analgesia.

    PubMed

    Craggs, Jason G; Price, Donald D; Verne, G Nicholas; Perlstein, William M; Robinson, Michael M

    2007-12-01

    Pain requires the integration of sensory, cognitive, and affective information. The use of placebo is a common methodological ploy in many fields, including pain. Neuroimaging studies of pain and placebo analgesia (PA) have yet to identify a mechanism of action. Because PA must result from higher order processes, it is likely influenced by cognitive and affective dimensions of the pain experience. A network of brain regions involved in these processes includes the anterior and posterior insula (A-Ins, P-Ins), dorsal anterior cingulate cortex (DACC), dorsolateral prefrontal cortex (DLPFC), and the supplementary motor area (SMA). We used connectivity analyses to investigate the underlying mechanisms associated with Placebo analgesia in a group of chronic pain patients. Structural equation models (SEM) of fMRI data evaluated the inter-regional connectivity of these regions across three conditions: (1) initial Baseline (B1), (2) placebo (PA), and (3) Placebo Match (PM). SEM results of B1 data in the left hemisphere confirmed hypothesized regional relationships. However, inter-regional relationships were dynamic and the network models varied across hemispheres and conditions. Deviations from the B1 model in the PA and PM conditions correspond to our manipulation of expectation for pain. The dynamic changes in inter-regional influence across conditions are interpreted in the context of a self-reinforcing feedback loop involved in the induction and maintenance of PA. Although it is likely that placebo analgesia results partly from afferent inhibition of a nociceptive signal, the mechanisms likely involve the interaction of a cognitive-affective network with input from both hemispheres. PMID:17904390

  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. Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice

    PubMed Central

    Balkowiec, Agnieszka; Katz, David M

    1998-01-01

    Molecular mechanisms underlying maturation of the central respiratory rhythm are largely unknown. Previously, we found that brain-derived neurotrophic factor (BDNF) is required for expression of normal breathing behaviour in newborn mice, raising the possibility that maturation of central respiratory output is dependent on BDNF. Respiratory activity was recorded in vitro from cervical ventral roots (C1 or C4) using the isolated brainstem–spinal cord preparation from postnatal day (P) 0.5–2.0 and P4.5 wild-type mice and mice lacking functional bdnf alleles. Loss of one or both bdnf alleles resulted in an approximately 50 % depression of central respiratory frequency compared with wild-type controls. In addition, respiratory cycle length variability was 214 % higher in bdnf null (bdnf−/−) animals compared with controls at P4.5. In contrast, respiratory burst duration was unaffected by bdnf gene mutation. These derangements of central respiratory rhythm paralleled the ventilatory depression and irregular breathing characteristic of bdnf mutants in vivo, indicating that central deficits can largely account for the abnormalities in resting ventilation produced by genetic loss of BDNF. BDNF is thus the first growth factor identified that is required for normal development of the central respiratory rhythm, including the stabilization of central respiratory output that occurs after birth. PMID:9706001

  9. 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.

  10. What the study of voice recognition in normal subjects and brain-damaged patients tells us about models of familiar people recognition.

    PubMed

    Gainotti, Guido

    2011-07-01

    In recent years it has been shown that a disorder in recognizing familiar people can be observed in patients with lesions affecting the anterior parts of the temporal lobes and that these disorders can be multi-modal, simultaneously affecting the visual, auditory and linguistic channels that allow person identification. Several authors have also shown that patients with right anterior temporal atrophy are more impaired in assessing familiarity and in retrieving person-specific semantic information from faces than from names, whereas the opposite pattern of performance can be observed in patients with left temporal lobe atrophy. Voice recognition disorders have been studied much less even despite their clinical and theoretical importance. The aim of the present review, therefore, was to compare recognition of familiar faces and voices, taking into account not only results obtained in individual patients with right anterior temporal lesions, but also those of group studies of unselected right- and left brain-damaged patients and results of experimental investigations conducted on face and voice recognition in normal subjects. Results of the review showed that: (1) voice recognition disorders are mainly due to right temporal lesions, similarly to face recognition disorders; (2) famous voice recognition disorders can be dissociated from unfamiliar voice discrimination impairments; (3) although face and voice recognition disorders tend to co-occur, they can also dissociate and in these patients there is a prevalent involvement of the right fusiform gyrus when face recognition disorders are on the foreground, and of the right superior temporal gyrus when voice recognition disorders are prominent; (4) normal subjects have greater difficulty evaluating familiarity and drawing semantic information from the voices than from the faces of celebrities. These data are at variance with models which assume that familiarity feelings may be generated at the level of person identity

  11. Deletion of the huntingtin proline-rich region does not significantly affect normal huntingtin function in mice

    PubMed Central

    Neveklovska, Michelle; Clabough, Erin B. D.; Steffan, Joan S.; Zeitlin, Scott O.

    2012-01-01

    The N-terminus of Huntingtin, the protein encoded by the Huntington’s disease gene, contains a stretch of polyglutamine residues that is expanded in Huntington’s disease. The polyglutamine stretch is flanked by two conserved protein domains in vertebrates: an N1-17 domain, and a proline-rich region (PRR). The PRR can modulate the structure of the adjacent polyglutamine stretch, and is a binding site for several interacting proteins. To determine the role of the PRR in Huntingtin function, we have generated a knock-in allele of the mouse Huntington’s disease gene homolog that expresses full-length normal huntingtin lacking the PRR. Mice that are homozygous for the huntingtin PRR deletion are born at the normal Mendelian frequency, suggesting that the PRR is not required for essential huntingtin functions during embryonic development. Moreover, adult homozygous mutants did not exhibit any significant differences from wild-type controls in general motor function and motor learning. However, 18 month-old male, but not female, homozygous PRR deletion mutants exhibited deficits in the Morris water task, suggesting that age-dependent spatial learning and memory may be affected in a sex-specific fashion by the huntingtin PRR deletion. PMID:22956985

  12. De novo development of gliomas in a child with neurofibromatosis type 1, fragile X and previously normal brain magnetic resonance imaging

    PubMed Central

    Zafar, Rabia; Hsiao, Esther Y.; Botteron, Kelly N.; McKinstry, Robert C.; Gutmann, David H.

    2016-01-01

    Fifteen to 20% of children with neurofibromatosis type 1 develop low-grade glial neoplasms. However, since neuroimaging is not routinely obtained until a child is clinically symptomatic, little is known about presymptomatic radiographic characteristics of gliomas in this at-risk population. Herein, we describe a child with neurofibromatosis type 1 who initially had normal brain imaging before the development of multifocal gliomas. Comparison of these serial images demonstrated that brain tumors can arise de novo in children with this cancer predisposition syndrome, further underscoring the limited prognostic value of normal baseline magnetic resonance imaging. PMID:26973730

  13. 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

  14. Quantitative sodium MRI of the human brain at 9.4 T provides assessment of tissue sodium concentration and cell volume fraction during normal aging.

    PubMed

    Thulborn, Keith; Lui, Elaine; Guntin, Jonathan; Jamil, Saad; Sun, Ziqi; Claiborne, Theodore C; Atkinson, Ian C

    2016-02-01

    Sodium ion homeostasis is a fundamental property of viable tissue, allowing the tissue sodium concentration to be modeled as the tissue cell volume fraction. The modern neuropathology literature using ex vivo tissue from selected brain regions indicates that human brain cell density remains constant during normal aging and attributes the volume loss that occurs with advancing age to changes in neuronal size and dendritic arborization. Quantitative sodium MRI performed with the enhanced sensitivity of ultrahigh-field 9.4 T has been used to investigate tissue cell volume fraction during normal aging. This cross-sectional study (n = 49; 21-80 years) finds that the in vivo tissue cell volume fraction remains constant in all regions of the brain with advancing age in individuals who remain cognitively normal, extending the ex vivo literature reporting constant neuronal cell density across the normal adult age range. Cell volume fraction, as measured by quantitative sodium MRI, is decreased in diseases of cell loss, such as stroke, on a time scale of minutes to hours, and in response to treatment of brain tumors on a time scale of days to weeks. Neurodegenerative diseases often have prodromal periods of decades in which regional neuronal cell loss occurs prior to clinical presentation. If tissue cell volume fraction can detect such early pathology, this quantitative parameter may permit the objective measurement of preclinical disease progression. This current study in cognitively normal aging individuals provides the basis for the pursuance of investigations directed towards such neurodegenerative diseases.

  15. 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. PMID:27544862

  16. LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain.

    PubMed

    Simón-Sánchez, Javier; Herranz-Pérez, Vicente; Olucha-Bordonau, Francisco; Pérez-Tur, Jordi

    2006-02-01

    The leucine-rich repeat kinase 2 (LRRK2) gene was recently found to have multiple mutations that are causative for autosomal dominant inherited Parkinson's disease (PD). Previously, we used Northern blot analysis to show that this gene was expressed in the cerebellum, cerebral cortex, medulla, spinal cord, occipital pole, frontal lobe, temporal lobe and caudate putamen. However, a more comprehensive map of LRRK2 mRNA localization in the central nervous system is still lacking. In this study we have mapped the distribution of the mRNA encoding for LRRK2 using nonradioactive in situ hybridization. We detected a moderate expression of this PD-related gene throughout the adult B2B6 mouse brain. A stronger hybridization signal was observed in deep cerebral cortex layers, superficial cingulate cortex layers, the piriform cortex, hippocampal formation, caudate putamen, substantia nigra, the basolateral and basomedial anterior amygdala nuclei, reticular thalamic nucleus and also in the cerebellar granular cell layer. Given that LRRK2 mRNA is highly enriched in motor systems and also is expressed in other systems, we may conclude that mutations in LRRK2 may affect several motor and nonmotor structures that may play an important role in the development of PD.

  17. Prenatal immune challenge affects growth, behavior, and brain dopamine in offspring.

    PubMed

    Bakos, Jan; Duncko, Roman; Makatsori, Aikaterini; Pirnik, Zdeno; Kiss, Alexander; Jezova, Daniela

    2004-06-01

    It is known that the development and plasticity of the neuroendocrine system can be affected by many factors, and that adverse events during the prenatal period can result in long-lasting changes in adulthood. This study was aimed at evaluating the possible consequences for offspring from chronic inflammation during pregnancy. Chronic inflammation was simulated by treatment with increasing doses of lipopolysaccharide (LPS) to dams on days 15 through 19 of pregnancy. Attempts were made to prevent possible negative alterations by keeping animals in an enriched environment (EE). Maternal exposure to LPS resulted in a significant reduction of body weight of male offspring during the weaning period. This difference remained until the age of 63 days in controls (C), but not in animals reared in EE. The content of dopamine in the nucleus accumbens was found to be lower in prenatally stressed (PS) adult males. Furthermore, prenatal exposure to maternal immune challenge was associated with lower locomotor activity in elevated plus maze and increased number of skips in the beam-walking test, as observed in female offspring. No differences in ACTH and corticosterone concentrations with regard to prenatal treatment were found; however, both groups kept in EE showed increased levels of corticosterone as well as enlarged adrenal glands. Thus, immune activation during pregnancy may induce long-term changes in brain catecholamines and behavior, but it is not harmful to basal hormone secretion in the offspring. PMID:15240379

  18. Some Attenuated Variants of Vesicular Stomatitis Virus Show Enhanced Oncolytic Activity against Human Glioblastoma Cells relative to Normal Brain Cells▿

    PubMed Central

    Wollmann, Guido; Rogulin, Vitaliy; Simon, Ian; Rose, John K.; van den Pol, Anthony N.

    2010-01-01

    Vesicular stomatitis virus (VSV) has been shown in laboratory studies to be effective against a variety of tumors, including malignant brain tumors. However, attenuation of VSV may be necessary to balance the potential toxicity toward normal cells, particularly when targeting brain tumors. Here we compared 10 recombinant VSV variants resulting from different attenuation strategies. Attenuations included gene shifting (VSV-p1-GFP/RFP), M protein mutation (VSV-M51), G protein cytoplasmic tail truncations (VSV-CT1/CT9), G protein deletions (VSV-dG-GFP/RFP), and combinations thereof (VSV-CT9-M51). Using in vitro viability and replication assays, the VSV variants were grouped into three categories, based on their antitumor activity and non-tumor-cell attenuation. In the first group, wild-type-based VSV-G/GFP, tumor-adapted VSV-rp30, and VSV-CT9 showed a strong antitumor profile but also retained some toxicity toward noncancer control cells. The second group, VSV-CT1, VSV-dG-GFP, and VSV-dG-RFP, had significantly diminished toxicity toward normal cells but showed little oncolytic action. The third group displayed a desired combination of diminished general toxicity and effective antitumor action; this group included VSV-M51, VSV-CT9-M51, VSV-p1-GFP, and VSV-p1-RFP. A member of the last group, VSV-p1-GFP, was then compared in vivo against wild-type-based VSV-G/GFP. Intranasal inoculation of young, postnatal day 16 mice with VSV-p1-GFP showed no adverse neurological effects, whereas VSV-G/GFP was associated with high lethality (80%). Using an intracranial tumor xenograft model, we further demonstrated that attenuated VSV-p1-GFP targets and kills human U87 glioblastoma cells after systemic application. We concluded that some, but not all, attenuated VSV mutants display a favorable oncolytic profile and merit further investigation. PMID:19906910

  19. 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. PMID:22643242

  20. Cerebral Blood Flow Changes in Glioblastoma Patients Undergoing Bevacizumab Treatment Are Seen in Both Tumor and Normal Brain

    PubMed Central

    Nagpal, Seema; Hippe, Daniel S; Ravanpay, Ali C; Schmiedeskamp, Heiko; Bammer, Roland; Palagallo, Gerald J; Recht, Lawrence; Zaharchuk, Greg

    2015-01-01

    Bevacizumab (BEV) is increasingly used to treat recurrent glioblastoma (GBM) with some reported improvement in neurocognitive function despite potential neurotoxicities. We examined the effects of BEV on cerebral blood flow (CBF) within recurrent GBM tumor and in the contralateral middle cerebral artery (MCA) territory. Post-chemoradiation patients with histologically confirmed GBM were treated with BEV and underwent routine, serial tumor imaging with additional pseudocontinuous arterial spin labeling (pcASL) following informed consent. Circular regions-of-interest were placed on pcASL images directly over the recurrent tumor and in the contralateral MCA territory. CBF changes before and during BEV treatment were evaluated in tumor and normal tissue. Linear mixed models were used to assess statistical significance. Fifty-three pcASL studies in 18 patients were acquired. Evaluation yielded lower mean tumoral CBF during BEV treatment compared with pre-treatment (45 ± 27 vs. 65 ± 27 ml/100 g/min, p = 0.002), and in the contralateral MCA territory during, compared with pre-BEV treatment (35 ± 8.4 vs. 41 ± 8.4 ml/100 g/min, p = 0.03). The decrease in mean CBF tended to be greater in the tumoral region than in the contralateral MCA, though the difference did not reach statistical significance (31% vs. 13%; p = 0.082). Conclusions BEV administration results in statistically significant global CBF decrease with a potentially preferential decrease in tumor perfusion compared with normal brain tissue. PMID:25923677

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

    PubMed

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

    2016-01-01

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

  2. 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

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

    PubMed

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

    2016-01-01

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

  4. 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.

  5. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume?

    PubMed

    Lemaitre, Herve; Goldman, Aaron L; Sambataro, Fabio; Verchinski, Beth A; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Mattay, Venkata S

    2012-03-01

    Normal aging is accompanied by global as well as regional structural changes. While these age-related changes in gray matter volume have been extensively studied, less has been done using newer morphological indexes, such as cortical thickness and surface area. To this end, we analyzed structural images of 216 healthy volunteers, ranging from 18 to 87 years of age, using a surface-based automated parcellation approach. Linear regressions of age revealed a concomitant global age-related reduction in cortical thickness, surface area and volume. Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy. No cortical regions showed more surface area reduction than the global average. The distinction between these morphological measures may provide valuable information to dissect age-related structural changes of the brain, with each of these indexes probably reflecting specific histological changes occurring during aging. PMID:20739099

  6. In a mouse model relevant for PTSD, selective brain steroidogenic stimulants (SBSSs) improve behavioral deficits by normalizing allopregnanolone biosynthesis

    PubMed Central

    Pinna, Graziano

    2010-01-01

    The pathophysiological role of the neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) in neuropsychiatric disorders has been highlighted in several recent investigations. For instance, allopregnanolone levels are decreased in the cerebrospinal fluid (CSF) of patients with posttraumatic stress disorder (PTSD) and major unipolar depression. Neurosteroidogenic antidepressants, including fluoxetine and analogs, correct this decrease in a manner that correlates with improved depressive symptoms. PTSD-like behavioral dysfunctions, including heightened aggression, exaggerated fear, and anxiety-like behavior associated with a decrease in corticolimbic allopregnanolone content are modeled in mice by protracted social isolation stress. Allopregnanolone is not only synthesized by principal glutamatergic and GABAergic neurons but also locally, potently, positively, and allosterically modulates GABA action at post- and extra-synaptic GABAA receptors. Hence, this paper will review preclinical studies which show that in socially-isolated mice, rather than SSRI mechanisms, allopregnanolone biosynthesis in glutamatergic corticolimbic neurons offers a non-traditional target for fluoxetine to decrease signs of aggression, normalize fear responses, and decrease anxiety-like behavior. At low SSRI-inactive doses, fluoxetine and related congeners potently increase allopregnanolone levels by acting as potent selective brain steroidogenic stimulants (SBSSs), thereby facilitating GABAA receptor neurotransmission and improving behavioral dysfunctions. Although the precise molecular mechanisms that underlie the action of these drugs are not fully understood, findings from socially-isolated mice may ultimately generate insights into novel drug targets for the treatment of psychiatric disorders, such as anxiety and panic disorders, depression, and PTSD. PMID:20716970

  7. Vitamin D as a neurosteroid affecting the developing and adult brain.

    PubMed

    Groves, Natalie J; McGrath, John J; Burne, Thomas H J

    2014-01-01

    Vitamin D deficiency is prevalent throughout the world, and growing evidence supports a requirement for optimal vitamin D levels for the healthy developing and adult brain. Vitamin D has important roles in proliferation and differentiation, calcium signaling within the brain, and neurotrophic and neuroprotective actions; it may also alter neurotransmission and synaptic plasticity. Recent experimental studies highlight the impact that vitamin D deficiency has on brain function in health and disease. In addition, results from recent animal studies suggest that vitamin D deficiency during adulthood may exacerbate underlying brain disorders and/or worsen recovery from brain stressors. An increasing number of epidemiological studies indicate that vitamin D deficiency is associated with a wide range of neuropsychiatric disorders and neurodegenerative diseases. Vitamin D supplementation is readily available and affordable, and this review highlights the need for further research. PMID:25033060

  8. Alpha-lipoic acid affects the oxidative stress in various brain structures in mice with methionine and choline deficiency.

    PubMed

    Veskovic, Milena; Mladenovic, Dusan; Jorgacevic, Bojan; Stevanovic, Ivana; de Luka, Silvio; Radosavljevic, Tatjana

    2015-04-01

    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.

  9. 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

  10. Transfer coefficients for L-valine and the rate of incorporation of L-(1-/sup 14/C) valine into proteins in normal adult rat brain

    SciTech Connect

    Kirikae, M.; Diksic, M.; Yamamoto, Y.L.

    1988-08-01

    An autoradiographic method for the measurement of the rate of valine incorporation into brain proteins is described. The transfer coefficients for valine into and out of the brain and the rate of valine incorporation into normal rat brain proteins are given. The valine incorporation and the transfer constants of valine between different biological compartments are provided for 14 gray matter and 2 white matter structures of an adult rat brain. The rate of valine incorporation varies between 0.52 +/- 0.19 nmol/g/min in white matter and 1.94 +/- 0.47 in inferior colliculus (gray matter). Generally, the rate of valine incorporation is about three to four times higher in the gray matter than in the white matter structures.

  11. Disruption of glucocorticoid signaling in chondrocytes delays metaphyseal fracture healing but does not affect normal cartilage and bone development

    PubMed Central

    Tu, Jinwen; Henneicke, Holger; Zhang, Yaqing; Stoner, Shihani; Cheng, Tegan L.; Schindeler, Aaron; Chen, Di; Tuckermann, Jan; Cooper, Mark S.; Seibel, Markus J.; Zhou, Hong

    2014-01-01

    States of glucocorticoid excess are associated with defects in chondrocyte function. Most prominently there is a reduction in linear growth but delayed healing of fractures that require endochondral ossification to also occur. In contrast, little is known about the role of endogenous glucocorticoids in chondrocyte function. As glucocorticoids exert their cellular actions through the glucocorticoid receptor (GR), we aimed to elucidate the role of endogenous glucocorticoids in chondrocyte function in vivo through characterization of tamoxifen-inducible chondrocyte-specific GR knockout (chGRKO) mice in which the GR was deleted at various post-natal ages. Knee joint architecture, cartilage structure, growth plates, intervertebral discs, long bone length and bone micro-architecture were similar in chGRKO and control mice at all ages. Analysis of fracture healing in chGRKO and control mice demonstrated that in metaphyseal fractures, chGRKO mice formed a larger cartilaginous callus at 1 and 2 week post-surgery, as well as a smaller amount of well-mineralized bony callus at the fracture site 4 week post-surgery, when compared to control mice. In contrast, chondrocyte-specific GR knockout did not affect diaphyseal fracture healing. We conclude that endogenous GC signaling in chondrocytes plays an important role during metaphyseal fracture healing but is not essential for normal long bone growth. PMID:25193158

  12. 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.

  13. 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

  14. Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Solé-Padullés, Cristina; Bartrés-Faz, David; Junqué, Carme; Vendrell, Pere; Rami, Lorena; Clemente, Imma C; Bosch, Beatriu; Villar, Amparo; Bargalló, Núria; Jurado, M Angeles; Barrios, Maite; Molinuevo, Jose Luis

    2009-07-01

    Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables. PMID:18053618

  15. 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.

  16. 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. PMID:24736861

  17. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-01

    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. PMID:26678032

  18. Pericyte abundance affects sucrose permeability in cultures of rat brain microvascular endothelial cells.

    PubMed

    Parkinson, Fiona E; Hacking, Cindy

    2005-07-01

    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.

  19. The Impact of Pre-Hospital Administration of Lactated Ringer's Solution versus Normal Saline in Patients with Traumatic Brain Injury.

    PubMed

    Rowell, Susan E; Fair, Kelly A; Barbosa, Ronald R; Watters, Jennifer M; Bulger, Eileen M; Holcomb, John B; Cohen, Mitchell J; Rahbar, Mohammad H; Fox, Erin E; Schreiber, Martin A

    2016-06-01

    Lactated Ringer's (LR) and normal saline (NS) are both used for resuscitation of injured patients. NS has been associated with increased resuscitation volume, blood loss, acidosis, and coagulopathy compared with LR. We sought to determine if pre-hospital LR is associated with improved outcome compared with NS in patients with and without traumatic brain injury (TBI). We included patients receiving pre-hospital LR or NS from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients with TBI (Abbreviated Injury Scale [AIS] head ≥3) and without TBI (AIS head ≤2) were compared. Cox proportional hazards models including Injury Severity Score (ISS), AIS head, AIS extremity, age, fluids, intubation status, and hospital site were generated for prediction of mortality. Linear regression models were generated for prediction of red blood cell (RBC) and crystalloid requirement, and admission biochemical/physiological parameters. Seven hundred ninety-one patients received either LR (n = 117) or NS (n = 674). Median ISS, AIS head, AIS extremity, and pre-hospital fluid volume were higher in TBI and non-TBI patients receiving LR compared with NS (p < 0.01). In patients with TBI (n = 308), LR was associated with higher adjusted mortality compared with NS (hazard rate [HR] = 1.78, confidence interval [CI] 1.04-3.04, p = 0.035). In patients without TBI (n = 483), no difference in mortality was demonstrated (HR = 1.49, CI 0.757-2.95, p = 0.247). Fluid type had no effect on admission biochemical or physiological parameters, 6-hour RBC, or crystalloid requirement in either group. LR was associated with increased mortality compared with NS in patients with TBI. These results underscore the need for a prospective randomized trial comparing pre-hospital LR with NS in patients with TBI.

  20. BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities.

    PubMed

    Griffanti, Ludovica; Zamboni, Giovanna; Khan, Aamira; Li, Linxin; Bonifacio, Guendalina; Sundaresan, Vaanathi; Schulz, Ursula G; Kuker, Wilhelm; Battaglini, Marco; Rothwell, Peter M; Jenkinson, Mark

    2016-11-01

    Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a "predominantly neurodegenerative" and a "predominantly vascular" cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies. PMID:27402600

  1. 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

  2. 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. PMID:25978461

  3. 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

  4. Dissecting the effects of endogenous brain IL-2 and normal versus autoreactive T lymphocytes on microglial responsiveness and T cell trafficking in response to axonal injury.

    PubMed

    Huang, Zhi; Meola, Danielle; Petitto, John M

    2012-09-27

    IL-2 is essential for T-helper regulatory (Treg) cell function and self-tolerance, and dysregulation of both endogenous brain and peripheral IL-2 gene expression may have important implications for neuronal injury and repair. We used an experimental approach combining mouse congenic breeding and immune reconstitution to test the hypothesis that the response of motoneurons to injury is modulated by the combined effects of IL2-mediated processes in the brain that modulate its endogenous neuroimmunological milieu, and IL2-mediated processes in the peripheral immune system that regulate T cell function (i.e., normal versus autoreactive Treg-deficient T cells). This experimental strategy enabled us to test our hypothesis by disentangling the effect of normal versus autoreactive T lymphocytes from the effect of endogenous brain IL-2 on microglial responsiveness (microglial phagocytic clusters normally associated with dead motoneurons and MHC2(+) activated microglia) and T cell trafficking, using the facial nerve axotomy model of injury. The results demonstrate that the loss of both brain and peripheral IL-2 had an additive effect on numbers of microglial phagocytic clusters at day 14 following injury, whereas the autoreactive status of peripheral T cells was the primary factor that determined the degree to which T cells entered the injured brain and contributed to increased microglial phagocytic clusters. Changes in activated MHC2(+) microglial in the injured FMN were associated with loss of endogenous brain IL-2 and/or peripheral IL-2. This model may provide greater understanding of the mechanisms involved in determining if T cells entering the injured central nervous system (CNS) have damaging or proregenerative effects.

  5. A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog

    PubMed Central

    Krahmer, Julia; Leopoldi, Alexandra; Artaker, Matthias; Pusch, Oliver; Zezula, Jürgen; Weissmann, Simon; Xie, Yunli; Schöfer, Christian; Schlederer, Michaela; Brosch, Gerald; Matthias, Patrick; Selfridge, Jim; Lassmann, Hans; Knoblich, Jürgen A.; Seiser, Christian

    2016-01-01

    The histone deacetylases HDAC1 and HDAC2 are crucial regulators of chromatin structure and gene expression, thereby controlling important developmental processes. In the mouse brain, HDAC1 and HDAC2 exhibit different developmental stage- and lineage-specific expression patterns. To examine the individual contribution of these deacetylases during brain development, we deleted different combinations of Hdac1 and Hdac2 alleles in neural cells. Ablation of Hdac1 or Hdac2 by Nestin-Cre had no obvious consequences on brain development and architecture owing to compensation by the paralog. By contrast, combined deletion of Hdac1 and Hdac2 resulted in impaired chromatin structure, DNA damage, apoptosis and embryonic lethality. To dissect the individual roles of HDAC1 and HDAC2, we expressed single alleles of either Hdac1 or Hdac2 in the absence of the respective paralog in neural cells. The DNA-damage phenotype observed in double knockout brains was prevented by expression of a single allele of either Hdac1 or Hdac2. Strikingly, Hdac1−/−Hdac2+/− brains showed normal development and no obvious phenotype, whereas Hdac1+/−Hdac2−/− mice displayed impaired brain development and perinatal lethality. Hdac1+/−Hdac2−/− neural precursor cells showed reduced proliferation and premature differentiation mediated by overexpression of protein kinase C, delta, which is a direct target of HDAC2. Importantly, chemical inhibition or knockdown of protein kinase C delta was sufficient to rescue the phenotype of neural progenitor cells in vitro. Our data indicate that HDAC1 and HDAC2 have a common function in maintaining proper chromatin structures and show that HDAC2 has a unique role by controlling the fate of neural progenitors during normal brain development. PMID:24449838

  6. Fresh frozen plasma resuscitation provides neuroprotection compared to normal saline in a large animal model of traumatic brain injury and polytrauma.

    PubMed

    Imam, Ayesha; Jin, Guang; Sillesen, Martin; Dekker, Simone E; Bambakidis, Ted; Hwabejire, John O; Jepsen, Cecilie H; Halaweish, Ihab; Alam, Hasan B

    2015-03-01

    We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2 h of shock (mean arterial pressure, 30-35 mm Hg), animals were resuscitated with normal saline (NS; 3×volume) or FFP (1×volume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9 mm(3); p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4 ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation.

  7. In normal rat, intraventricularly administered insulin-like growth factor-1 is rapidly cleared from CSF with limited distribution into brain

    PubMed Central

    Nagaraja, Tavarekere N; Patel, Padma; Gorski, Martin; Gorevic, Peter D; Patlak, Clifford S; Fenstermacher, Joseph D

    2005-01-01

    Background Putatively active drugs are often intraventricularly administered to gain direct access to brain and circumvent the blood-brain barrier. A few studies on the normal central nervous system (CNS) have shown, however, that the distribution of materials after intraventricular injections is much more limited than presumed and their exit from cerebrospinal fluid (CSF) is more rapid than generally believed. In this study, we report the intracranial distribution and the clearance from CSF and adjacent CNS tissue of radiolabeled insulin-like growth factor-1 after injection into one lateral ventricle of the normal rat brain. Methods Under barbiturate anesthesia, 125I-labeled insulin-like growth factor-1 (IGF-1) was injected into one lateral ventricle of normal Sprague-Dawley rats. The subsequent distribution of IGF-1 through the cerebrospinal fluid (CSF) system and into brain, cerebral blood vessels, and systemic blood was measured over time by gamma counting and quantitative autoradiography (QAR). Results Within 5 min of infusion, IGF-1 had spread from the infused lateral ventricle into and through the third and fourth ventricles. At this time, 25% of the infused IGF-1 had disappeared from the CSF-brain-meningeal system; the half time of this loss was 12 min. The plasma concentration of cleared IGF-1 was, however, very low from 2 to 9 min and only began to rise markedly after 20 min. This delay between loss and gain plus the lack of radiotracer in the cortical subarachnoid space suggested that much of the IGF-1 was cleared into blood via the cranial and/or spinal nerve roots and their associated lymphatic systems rather than periventricular tissue and arachnoid villi. Less than 10% of the injected radioactivity remained in the CSF-brain system after 180 min. The CSF and arteries and arterioles within the subarachnoid cisterns were labeled with IGF-1 within 10 min. Between 60 and 180 min, most of the radioactivity within the cranium was retained within and around

  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. Autoantibodies Affect Brain Density Reduction in Nonneuropsychiatric Systemic Lupus Erythematosus Patients

    PubMed Central

    Xu, Jian; Cheng, Yuqi; Lai, Aiyun; Lv, Zhaoping; Yu, Hongjun; Luo, Chunrong; Shan, Baoci; Xu, Lin; Xu, Xiufeng

    2015-01-01

    This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE). Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD) and white matter (WMD) were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA), and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL) or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients. PMID:26090505

  10. Deletion of TRAAK Potassium Channel Affects Brain Metabolism and Protects against Ischemia

    PubMed Central

    Laigle, Christophe; Confort-Gouny, Sylviane; Le Fur, Yann; Cozzone, Patrick J.; Viola, Angèle

    2012-01-01

    Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K+ channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K+ channel, is involved in the pathophysiology of brain ischemia. We studied the effects of TRAAK deletion on brain morphology and metabolism under physiological conditions, and during temporary focal cerebral ischemia in Traak−/− mice using a combination of in vivo magnetic resonance imaging (MRI) techniques and multinuclear magnetic resonance spectroscopy (MRS) methods. We provide the first in vivo evidence establishing a link between TRAAK and neurometabolism. Under physiological conditions, Traak−/− mice showed a particular metabolic phenotype characterized by higher levels of taurine and myo-inositol than Traak+/+ mice. Upon ischemia, Traak−/− mice had a smaller infarcted volume, with lower contribution of cellular edema than Traak+/+ mice. Moreover, brain microcirculation was less damaged, and brain metabolism and pH were preserved. Our results show that expression of TRAAK strongly influences tissue levels of organic osmolytes. Traak−/− mice resilience to cellular edema under ischemia appears related to their physiologically high levels of myo-inositol and of taurine, an aminoacid involved in the modulation of mitochondrial activity and cell death. The beneficial effects of TRAAK deletion designate this channel as a promising pharmacological target for the treatment against stroke. PMID:23285272

  11. 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

  12. 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.

  13. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.

    PubMed

    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

  14. The log-dynamic brain: how skewed distributions affect network operations

    PubMed Central

    Buzsáki, György; Mizuseki, Kenji

    2014-01-01

    We often assume that the variables of functional and structural brain parameters — such as synaptic weights, the firing rates of individual neurons, the synchronous discharge of neural populations, the number of synaptic contacts between neurons and the size of dendritic boutons — have a bell-shaped distribution. However, at many physiological and anatomical levels in the brain, the distribution of numerous parameters is in fact strongly skewed with a heavy tail, suggesting that skewed (typically lognormal) distributions are fundamental to structural and functional brain organization. This insight not only has implications for how we should collect and analyse data, it may also help us to understand how the different levels of skewed distributions — from synapses to cognition — are related to each other. PMID:24569488

  15. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

    PubMed

    Méndez-Couz, Marta; González-Pardo, Héctor; Vallejo, Guillermo; Arias, Jorge L; Conejo, Nélida M

    2016-10-01

    Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.

  16. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

    PubMed

    Méndez-Couz, Marta; González-Pardo, Héctor; Vallejo, Guillermo; Arias, Jorge L; Conejo, Nélida M

    2016-10-01

    Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc. PMID:27102086

  17. 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.

  18. 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. PMID:17920932

  19. P-glycoprotein activity in the blood-brain barrier is affected by virus-induced neuroinflammation and antipsychotic treatment.

    PubMed

    Doorduin, Janine; de Vries, Erik F J; Dierckx, Rudi A; Klein, Hans C

    2014-10-01

    A large percentage of schizophrenic patients respond poorly to antipsychotic treatment. This could be explained by inefficient drug transport across the blood-brain barrier due to P-glycoprotein mediated efflux. P-glycoprotein activity and expression in the blood-brain barrier can be affected by inflammation and pharmacotherapy. We therefore investigated the effect of herpes simplex virus type-1 (HSV-1) induced neuroinflammation and antipsychotic treatment on P-glycoprotein activity. Rats were inoculated with HSV-1 or PBS (control) on day 0 and treated with saline, clozapine or risperidone from day 0 up until day 4 post-inoculation. Positron emission tomography with the P-glycoprotein substrate [11C]verapamil was used to assess P-glycoprotein activity at day 6 post-inoculation. Disease symptoms in HSV-1 inoculated rats increased over time and were not significantly affected by treatment. The volume of distribution (VT) of [11C]verapamil was significantly lower (10-22%) in HSV-1 inoculated rats than in control rats. In addition, antipsychotic treatment significantly affected the VT of [11C]verapamil in all brain regions, although this effect was drug dependent. In fact, VT of [11C]verapamil was significantly increased (22-39%) in risperidone treated rats in most brain regions when compared to clozapine treated rats and in midbrain when compared to saline treated rats. No interaction between HSV-1 inoculation and antipsychotic treatment on VT of [11C]verapamil was found. In this study we demonstrated that HSV-1 induced neuroinflammation increased and risperidone treatment decreased P-glycoprotein activity. This finding is of importance for the understanding of treatment resistance in schizophrenia, and warrants further investigation of the underlying mechanism and the importance in clinical practice.

  20. Moderate elevations in international normalized ratio should not lead to delays in neurosurgical intervention in patients with traumatic brain injury

    PubMed Central

    Rowell, Susan E.; Barbosa, Ronald R.; Lennox, Tori C.; Fair, Kelly A.; Rao, Abigail J.; Underwood, Samantha J.; Schreiber, Martin A.

    2015-01-01

    BACKGROUND The management of severe traumatic brain injury (TBI) frequently involves invasive intracranial monitoring or cranial surgery. In our institution, intracranial procedures are often deferred until an international normalized ratio (INR) of less than 1.4 is achieved. There is no evidence that a moderately elevated INR is associated with increased risk of bleeding in patients undergoing neurosurgical intervention (NI). Thrombelastography (TEG) provides a functional assessment of clotting and has been shown to better predict clinically relevant coagulopathy compared with INR. We hypothesized that in patients with TBI, an elevated INR would result in increased time to NI and would not be associated with coagulation abnormalities based on TEG. METHODS A secondary analysis of prospectively collected data was performed in trauma patients with intracranial hemorrhage that underwent NI (defined as cranial surgery or intracranial pressure monitoring) within 24 hours of arrival. Time from admission to NI was recorded. TEG and routine coagulation assays were obtained at admission. Patients were considered hypocoagulable based on INR if their admission INR was greater than 1.4 (high INR). Manufacturer-specified values were used to determine hypocoagulability for each TEG variable. RESULTS Sixty-one patients (median head Abbreviated Injury Scale [AIS] score, 5) met entry criteria, of whom 16% had high INR. Demographic, physiologic, and injury scoring data were similar between groups. The median time to NI was longer in patients with high INR (358 minutes vs. 184 minutes, p = 0.027). High-INR patients were transfused more plasma than patients with an INR of 1.4 or less (2 U vs. 0 U, p = 0.01). There was no association between an elevated INR and hypocoagulability based on TEG. CONCLUSION TBI patients with an admission INR of greater than 1.4 had a longer time to NI. The use of plasma transfusion to decrease the INR may have contributed to this delay. A moderately

  1. 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

  2. Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: investigation of the role of gender.

    PubMed

    Moreira, Ana C; Silva, Ana M; Santos, Maria S; Sardão, Vilma A

    2013-03-01

    Resveratrol (3,5,4'-trihydroxy-trans stilbene) is commonly recognized by its antioxidant properties. Despite its beneficial qualities, the toxic effects of this natural compound are still unknown. Since mitochondria are essential to support the energy-dependent regulation of several cell functions, the objective of this study was to evaluate resveratrol effects on rat brain and liver mitochondrial fractions from male and females regarding oxidative stress and bioenergetics. No basal differences were observed between mitochondrial fractions from males and females, except in liver mitochondria, the generation of H(2)O(2) by the respiratory chain is lower for female preparations. Resveratrol inhibited lipid peroxidation in preparations from both genders and organs. Furthermore, brain mitochondria in both gender groups appeared susceptible to resveratrol as seen by a decrease in state 3 respiration and alterations in mitochondrial membrane potential fluctuations during ADP phosphorylation. As opposed, liver mitochondria were less affected by resveratrol. Our data also demonstrates that resveratrol inhibits complex I activity in all mitochondrial preparations. The results suggest that brain mitochondria appear to be more susceptible to resveratrol effects, and gender appears to play a minor role. It remains to be determined if resveratrol effects on brain mitochondria contribute to deterioration of mitochondrial function or instead to mediate hormesis-mediated events.

  3. Chronic social isolation affects thigmotaxis and whole-brain serotonin levels in adult zebrafish.

    PubMed

    Shams, Soaleha; Chatterjee, Diptendu; Gerlai, Robert

    2015-10-01

    The popularity of the zebrafish has been growing in behavioral brain research. Previously utilized mainly in developmental biology and genetics, the zebrafish has turned out to possess a complex behavioral repertoire. For example, it is a highly social species, and individuals form tight groups, a behavior called shoaling. Social isolation induced changes in brain function and behavior have been demonstrated in a variety of laboratory organisms. However, despite its highly social nature, the zebrafish has rarely been utilized in this research area. Here, we investigate the effects of chronic social isolation (lasting 90 days) on locomotor activity and anxiety-related behaviors in an open tank. We also examine the effect of chronic social isolation on levels of whole-brain serotonin and dopamine and their metabolites. We found that long-term social deprivation surprisingly decreased anxiety-related behavious during open-tank testing but had no effect on locomotor activity. We also found that serotonin levels, decreased significantly in socially isolated fish, but levels of dopamine and metabolites of these neurotransmitters 5HIAA and DOPAC, respectively, remained unchanged. Our results imply that the standard high density housing employed in most zebrafish laboratories may not be the optimal way to keep these fish, and open a new avenue towards the analysis of the biological mechanisms of social behavior and of social deprivation induced changes in brain function using this simple vertebrate model organism.

  4. 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…

  5. 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…

  6. Distinct Brain Systems Underlie the Processing of Valence and Arousal of Affective Pictures

    ERIC Educational Resources Information Center

    Nielen, M. M. A.; Heslenfeld, D. J.; Heinen, K.; Van Strien, J. W.; Witter, M. P.; Jonker, C.; Veltman, D. J.

    2009-01-01

    Valence and arousal are thought to be the primary dimensions of human emotion. However, the degree to which valence and arousal interact in determining brain responses to emotional pictures is still elusive. This functional MRI study aimed to delineate neural systems responding to valence and arousal, and their interaction. We measured neural…

  7. 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…

  8. 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

  9. 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. PMID:23954779

  10. 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.

  11. Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

    PubMed Central

    Brock, Christina; Søfteland, Eirik; Gunterberg, Veronica; Frøkjær, Jens Brøndum; Lelic, Dina; Brock, Birgitte; Dimcevski, Georg; Gregersen, Hans; Simrén, Magnus; Drewes, Asbjørn Mohr

    2013-01-01

    OBJECTIVE Long-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms. RESEARCH DESIGN AND METHODS Fifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected. RESULTS Diabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P ≤ 0.001), and showed diminished amplitude of the N2–P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P ≤ 0.001). CONCLUSIONS This study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved

  12. Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [18F]-Florbetaben PET Quantitation in Alzheimer's Model Mice

    PubMed Central

    Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

    2016-01-01

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [18F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (Rmean = 0.75) was slightly superior to the brainstem (Rmean = 0.74) and the cerebellum (Rmean = 0.73). Automated brain

  13. The Cell Birth Marker BrdU Does Not Affect Recruitment of Subsequent Cell Divisions in the Adult Avian Brain

    PubMed Central

    Cattan, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [3H]-thymidine+ neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [3H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [3H]-thymidine+ neurons. The number of silver grains per [3H]-thymidine+ neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  14. Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain.

    PubMed Central

    Crain, B. J.; Hu, W.; Sze, C. I.; Slunt, H. H.; Koo, E. H.; Price, D. L.; Thinakaran, G.; Sisodia, S. S.

    1996-01-01

    Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous amyloid precursor-like proteins. In the present study we report on the expression and distribution of APLP-2 in fetal and adult human brain and in brains of patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding isoforms predicted to undergo post-translational modification by chondroitin sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the brains of young adults. Immunocytochemical labeling with APLP-2-specific antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in neurons and astrocytes, in large part overlapping the distribution of the amyloid precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous in large dystrophic neurites that also label with antibodies specific for APP and chromogranin A. In view of the age-dependent increase in levels of chondroitin sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2 may play roles in neuronal sprouting or in the aggregation, deposition, and/or persistence of beta-amyloid deposits. Images Figure 1 Figure 2 Figure 3 PMID:8863657

  15. 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

  16. A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development.

    PubMed

    Lebel, Catherine; Mattson, Sarah N; Riley, Edward P; Jones, Kenneth L; Adnams, Colleen M; May, Philip A; Bookheimer, Susan Y; O'Connor, Mary J; Narr, Katherine L; Kan, Eric; Abaryan, Zvart; Sowell, Elizabeth R

    2012-10-31

    Exposure to alcohol in utero can cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering "experience" over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders. PMID:23115162

  17. 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.

  18. Serendipity and the Siamese cat: the discovery that genes for coat and eye pigment affect the brain.

    PubMed

    Kaas, Jon H

    2005-01-01

    One day in the late 1960s, Ray Guillery was examining brain sections through the visual thalamus of cats, and he recognized that the arrangement of layers in the lateral geniculate nucleus (LGN) of one cat was strangely abnormal. The cat was identified as a Siamese cat, one of a breed selected for its unusual coat color, with reduced pigment over much of the body and eyes. This chance observation and the recognition of its significance led to a broad-ranging series of investigations. These experiments showed that the lack of normal levels of pigment in the retina in Siamese cats (and other hypopigmented mammals) was the critical factor in the misdirection of many of the projections of the retina to the brain, the nature of the projection error, and the developmental consequences of the relay of the misdirected retinal inputs to visual cortex. As a result, we have a better understanding of how the brain forms proper connections and of the neural basis of visual problems in albino humans.

  19. 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.

  20. Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

    PubMed

    Heldmann, Marcus; Berding, Georg; Voges, Jürgen; Bogerts, Bernhard; Galazky, Imke; Müller, Ulf; Baillot, Gunther; Heinze, Hans-Jochen; Münte, Thomas F

    2012-01-01

    The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control. PMID:22629317

  1. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    PubMed

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia.

  2. 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

  3. 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

  4. 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

  5. Brain Mechanisms for Processing Affective (and Nonaffective) Touch Are Atypical in Autism.

    PubMed

    Kaiser, Martha D; Yang, Daniel Y-J; Voos, Avery C; Bennett, Randi H; Gordon, Ilanit; Pretzsch, Charlotte; Beam, Danielle; Keifer, Cara; Eilbott, Jeffrey; McGlone, Francis; Pelphrey, Kevin A

    2016-06-01

    C-tactile (CT) afferents encode caress-like touch that supports social-emotional development, and stimulation of the CT system engages the insula and cortical circuitry involved in social-emotional processing. Very few neuroimaging studies have investigated the neural mechanisms of touch processing in people with autism spectrum disorder (ASD), who often exhibit atypical responses to touch. Using functional magnetic resonance imaging, we evaluated the hypothesis that children and adolescents with ASD would exhibit atypical brain responses to CT-targeted touch. Children and adolescents with ASD, relative to typically developing (TD) participants, exhibited reduced activity in response to CT-targeted (arm) versus non-CT-targeted (palm) touch in a network of brain regions known to be involved in social-emotional information processing including bilateral insula and insular operculum, the right posterior superior temporal sulcus, bilateral temporoparietal junction extending into the inferior parietal lobule, right fusiform gyrus, right amygdala, and bilateral ventrolateral prefrontal cortex including the inferior frontal and precentral gyri, suggesting atypical social brain hypoactivation. Individuals with ASD (vs. TD) showed an enhanced response to non-CT-targeted versus CT-targeted touch in the primary somatosensory cortex, suggesting atypical sensory cortical hyper-reactivity. PMID:26048952

  6. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging.

    PubMed

    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.

  7. 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

  8. 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. PMID:26468140

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. How mild traumatic brain injury may affect declarative memory performance in the post-acute stage.

    PubMed

    Stulemeijer, Maja; Vos, Pieter E; van der Werf, Sieberen; van Dijk, Gert; Rijpkema, Mark; Fernández, Guillén

    2010-09-01

    Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia.

  14. Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+,K+-ATPase in rats.

    PubMed

    Christian, Brandon; McConnaughey, Kenneth; Bethea, Elena; Brantley, Scott; Coffey, Amy; Hammond, Leigha; Harrell, Shelly; Metcalf, Kasee; Muehlenbein, Danielle; Spruill, Willie; Brinson, Leslie; McConnaughey, Mona

    2004-05-01

    This study demonstrated that chronic aspartame consumption in rats can lead to altered T-maze performance and increased muscarinic cholinergic receptor densities in certain brain regions. Control and treated rats were trained in a T-maze to a particular side and then periodically tested to see how well they retained the learned response. Rats that had received aspartame (250 mg/kg/day) in the drinking water for 3 or 4 months showed a significant increase in time to reach the reward in the T-maze, suggesting a possible effect on memory due to the artificial sweetener. Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label muscarinic cholinergic receptors and atropine (10(-6) M) to determine nonspecific binding in whole-brain preparations, aspartame-treated rats showed a 31% increase in receptor numbers when compared to controls. In aspartame-treated rats, there was a significant increase in muscarinic receptor densities in the frontal cortex, midcortex, posterior cortex, hippocampus, hypothalamus and cerebellum of 80%, 60%, 61%, 65%, 66% and 60%, respectively. The midbrain was the only area where preparations from aspartame-treated rats showed a significant increase in Na(+),K(+)-ATPase activity. It can be concluded from these data that long-term consumption of aspartame can affect T-maze performance in rats and alter receptor densities or enzymes in brain.

  15. Tracking the dynamics of the social brain: ERP approaches for social cognitive and affective neuroscience.

    PubMed

    Amodio, David M; Bartholow, Bruce D; Ito, Tiffany A

    2014-03-01

    Event-related potential (ERP) approaches to social cognitive and affective neuroscience (SCAN) are not as widely used as other neuroimaging techniques, yet they offer several unique advantages. In particular, the high temporal resolution of ERP measures of neural activity make them ideally suited for studying the dynamic interplay of rapidly unfolding cognitive and affective processes. In this article, we highlight the utility of ERP methods for scientists investigating questions of SCAN. We begin with a brief description of the physiological basis of ERPs and discussion of methodological practices. We then discuss how ERPs may be used to address a range of questions concerning social perception, social cognition, attitudes, affect and self-regulation, with examples of research that has used the ERP approach to contribute important theoretical advances in these areas. Whether used alone or in combination with other techniques, the ERP is an indispensable part of the social and affective neuroscientist's methodological toolkit.

  16. Tracking the dynamics of the social brain: ERP approaches for social cognitive and affective neuroscience

    PubMed Central

    Amodio, David M.; Ito, Tiffany A.

    2014-01-01

    Event-related potential (ERP) approaches to social cognitive and affective neuroscience (SCAN) are not as widely used as other neuroimaging techniques, yet they offer several unique advantages. In particular, the high temporal resolution of ERP measures of neural activity make them ideally suited for studying the dynamic interplay of rapidly unfolding cognitive and affective processes. In this article, we highlight the utility of ERP methods for scientists investigating questions of SCAN. We begin with a brief description of the physiological basis of ERPs and discussion of methodological practices. We then discuss how ERPs may be used to address a range of questions concerning social perception, social cognition, attitudes, affect and self-regulation, with examples of research that has used the ERP approach to contribute important theoretical advances in these areas. Whether used alone or in combination with other techniques, the ERP is an indispensable part of the social and affective neuroscientist’s methodological toolkit. PMID:24319116

  17. 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.

  18. 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

  19. The Molecular Mechanisms Affecting N-Acetylaspartate Homeostasis Following Experimental Graded Traumatic Brain Injury

    PubMed Central

    Di Pietro, Valentina; Amorini, Angela Maria; Tavazzi, Barbara; Vagnozzi, Roberto; Logan, Ann; Lazzarino, Giacomo; Signoretti, Stefano; Lazzarino, Giuseppe; Belli, Antonio

    2014-01-01

    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. PMID:24515258

  20. 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.

  1. Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain.

    PubMed

    Smith, Craig M; Shen, Pei-Juan; Banerjee, Avantika; Bonaventure, Pascal; Ma, Sherie; Bathgate, Ross A D; Sutton, Steven W; Gundlach, Andrew L

    2010-10-01

    Relaxin-3 (RLN3) and its native receptor, relaxin family peptide 3 receptor (RXFP3), constitute a newly identified neuropeptide system enriched in mammalian brain. The distribution of RLN3/RXFP3 networks in rat brain and recent experimental studies suggest a role for this system in modulation of arousal, stress, metabolism, and cognition. In order to facilitate exploration of the biology of RLN3/RXFP3 in complementary murine models, this study mapped the neuroanatomical distribution of the RLN3/RXFP3 system in mouse brain. Adult, male wildtype and RLN3 knock-out (KO)/LacZ knock-in (KI) mice were used to map the central distribution of RLN3 gene expression and RLN3-like immunoreactivity (-LI). The distribution of RXFP3 mRNA and protein was determined using [(35)S]-oligonucleotide probes and a radiolabeled RXFP3-selective agonist ([(125)I]-R3/I5), respectively. High densities of neurons expressing RLN3 mRNA, RLN3-associated beta-galactosidase activity and RLN3-LI were detected in the nucleus incertus (or nucleus O), while smaller populations of positive neurons were observed in the pontine raphé, the periaqueductal gray and a region adjacent to the lateral substantia nigra. RLN3-LI was observed in nerve fibers/terminals in nucleus incertus and broadly throughout the pons, midbrain, hypothalamus, thalamus, septum, hippocampus, and neocortex, but was absent in RLN3 KO/LacZ KI mice. This RLN3 neural network overlapped the regional distribution of RXFP3 mRNA and [(125)I]-R3/I5 binding sites in wildtype and RLN3 KO/LacZ KI mice. These findings provide further evidence for the conserved nature of RLN3/RXFP3 systems in mammalian brain and the ability of RLN3/RXFP3 signaling to modulate "behavioral state" and an array of circuits involved in arousal, stress responses, affective state, and cognition.

  2. The gene vitellogenin affects microRNA regulation in honey bee (Apis mellifera) fat body and brain.

    PubMed

    Nunes, Francis M F; Ihle, Kate E; Mutti, Navdeep S; Simões, Zilá L P; Amdam, Gro V

    2013-10-01

    In honey bees, vitellogenin (Vg) is hypothesized to be a major factor affecting hormone signaling, food-related behavior, immunity, stress resistance and lifespan. MicroRNAs, which play important roles in post-transcriptional gene regulation, likewise affect many biological processes. The actions of microRNAs and Vg are known to intersect in the context of reproduction; however, the role of these associations on social behavior is unknown. The phenotypic effects of Vg knockdown are best established and studied in the forager stage of workers. Thus, we exploited the well-established RNA interference (RNAi) protocol for Vg knockdown to investigate its downstream effects on microRNA population in honey bee foragers' brain and fat body tissue. To identify microRNAs that are differentially expressed between tissues in control and knockdown foragers, we used μParaflo microfluidic oligonucleotide microRNA microarrays. Our results showed that 76 and 74 microRNAs were expressed in the brain of control and knockdown foragers whereas 66 and 69 microRNAs were expressed in the fat body of control and knockdown foragers, respectively. Target prediction identified potential seed matches for a differentially expressed subset of microRNAs affected by Vg knockdown. These candidate genes are involved in a broad range of biological processes including insulin signaling, juvenile hormone (JH) and ecdysteroid signaling previously shown to affect foraging behavior. Thus, here we demonstrate a causal link between the Vg knockdown forager phenotype and variation in the abundance of microRNAs in different tissues, with possible consequences for the regulation of foraging behavior.

  3. Dietary amylose-amylopectin starch content affects glucose and lipid metabolism in adipocytes of normal and diabetic rats.

    PubMed

    Kabir, M; Rizkalla, S W; Champ, M; Luo, J; Boillot, J; Bruzzo, F; Slama, G

    1998-01-01

    The aim of this study was to evaluate the effects of the chronic consumption of two starches, characterized by different glycemic indices and amylose-amylopectin content, on glucose metabolism in rat epididymal adipocytes. The two chosen starches were from mung bean (32% amylose) and cornstarch (0.5% amylose). The alpha-amylase digestibility was higher for the waxy cornstarch than that of the mung bean starch (60 +/- 4 vs. 45 +/- 3%, mean +/- SEM, respectively). The glycemic index of the waxy cornstarch diet (575 g starch /kg diet) was higher than that of the mung bean starch diet (107 +/- 7 vs. 67 +/- 5%, P < 0.01) when measured in vivo in two groups of normal rats (n = 9). In a subsequent study, normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats (18 per group) consumed a diet containing 575 g starch/kg diet as either waxy cornstarch or mung bean starch. After 3 wk, food intake, epididymal fat pad weights, and plasma glucose, insulin and triglyceride concentrations did not differ between diet groups. Adipocyte diameter was smaller in rats that consumed mung bean starch compared with those that consumed the waxy cornstarch diet (P < 0.01). The mung bean diet increased maximal insulin-stimulated 14C-glucose oxidation (% of basal values, P < 0. 05). In contrast, incorporation of 14C-glucose into total lipids was significantly lower in rats that consumed the mung bean diet (P < 0. 05). We conclude that in both normal and diabetic rats, the chronic replacement of a high glycemic index starch by a low glycemic index one in a mixed diet increases insulin-stimulated glucose oxidation, decreases glucose incorporation into total lipids and decreases epididymal adipocyte diameter. Thus, the type of starch mixed into the diet has important metabolic consequences at the cellular level in both normal and diabetic rats.

  4. How did the Elimination of the Earnings Test above the Normal Retirement Age affect Retirement Expectations?1

    PubMed Central

    Michaud, Pierre-Carl

    2010-01-01

    We look at the effect of the 2000 repeal of the earnings test above the normal retirement age on retirement expectations of workers in the Health and Retirement Study, aged 51 to 61 in 1992. For men, we find that those whose marginal wage rate increased when the earnings test was repealed, had the largest increase in the probability to work full-time past normal retirement age. We do not find significant evidence of effects of the repeal of the earnings test on the probability to work past age 62 or the expected claiming age. On the other hand, for those reaching the normal retirement age, deviations between the age at which Social Security benefits are actually claimed and the previously reported expected age are more negative in 2000 than in 1998. Since our calculations show that the tax introduced by the earnings test was small when accounting for actuarial benefit adjustments and differential mortality, our results suggest that although male workers form expectations in a way consistent with forward-looking behavior, they misperceive the complicated rules of the earnings test. Results for females suggest similar patterns but estimates are imprecise. PMID:21037938

  5. Initial contact of glioblastoma cells with existing normal brain endothelial cells strengthen the barrier function via fibroblast growth factor 2 secretion: a new in vitro blood-brain barrier model.

    PubMed

    Toyoda, Keisuke; Tanaka, Kunihiko; Nakagawa, Shinsuke; Thuy, Dinh Ha Duy; Ujifuku, Kenta; Kamada, Kensaku; Hayashi, Kentaro; Matsuo, Takayuki; Nagata, Izumi; Niwa, Masami

    2013-05-01

    Glioblastoma multiforme (GBM) cells invade along the existing normal capillaries in brain. Normal capillary endothelial cells function as the blood-brain barrier (BBB) that limits permeability of chemicals into the brain. To investigate whether GBM cells modulate the BBB function of normal endothelial cells, we developed a new in vitro BBB model with primary cultures of rat brain endothelial cells (RBECs), pericytes, and astrocytes. Cells were plated on a membrane with 8 μm pores, either as a monolayer or as a BBB model with triple layer culture. The BBB model consisted of RBEC on the luminal side as a bottom, and pericytes and astrocytes on the abluminal side as a top of the chamber. Human GBM cell line, LN-18 cells, or lung cancer cell line, NCI-H1299 cells, placed on either the RBEC monolayer or the BBB model increased the transendothelial electrical resistance (TEER) values against the model, which peaked within 72 h after the tumor cell application. The TEER value gradually returned to baseline with LN-18 cells, whereas the value quickly dropped to the baseline in 24 h with NCI-H1299 cells. NCI-H1299 cells invaded into the RBEC layer through the membrane, but LN-18 cells did not. Fibroblast growth factor 2 (FGF-2) strengthens the endothelial cell BBB function by increased occludin and ZO-1 expression. In our model, LN-18 and NCI-H1299 cells secreted FGF-2, and a neutralization antibody to FGF-2 inhibited LN-18 cells enhanced BBB function. These results suggest that FGF-2 would be a novel therapeutic target for GBM in the perivascular invasive front.

  6. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers

    PubMed Central

    Zlatar, Zvinka Z.; Bischoff-Grethe, Amanda; Hays, Chelsea C.; Liu, Thomas T.; Meloy, M. J.; Rissman, Robert A.; Bondi, Mark W.; Wierenga, Christina E.

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk. PMID:27445794

  7. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers.

    PubMed

    Zlatar, Zvinka Z; Bischoff-Grethe, Amanda; Hays, Chelsea C; Liu, Thomas T; Meloy, M J; Rissman, Robert A; Bondi, Mark W; Wierenga, Christina E

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk.

  8. In Silico Neuro-Oncology: Brownian Motion-Based Mathematical Treatment as a Potential Platform for Modeling the Infiltration of Glioma Cells into Normal Brain Tissue

    PubMed Central

    Antonopoulos, Markos; Stamatakos, Georgios

    2015-01-01

    Intensive glioma tumor infiltration into the surrounding normal brain tissues is one of the most critical causes of glioma treatment failure. To quantitatively understand and mathematically simulate this phenomenon, several diffusion-based mathematical models have appeared in the literature. The majority of them ignore the anisotropic character of diffusion of glioma cells since availability of pertinent truly exploitable tomographic imaging data is limited. Aiming at enriching the anisotropy-enhanced glioma model weaponry so as to increase the potential of exploiting available tomographic imaging data, we propose a Brownian motion-based mathematical analysis that could serve as the basis for a simulation model estimating the infiltration of glioblastoma cells into the surrounding brain tissue. The analysis is based on clinical observations and exploits diffusion tensor imaging (DTI) data. Numerical simulations and suggestions for further elaboration are provided. PMID:26309390

  9. Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes

    PubMed Central

    Hill, Robert A; Tong, Lei; Yuan, Peng; Murikinati, Sasidhar; Gupta, Shobhana; Grutzendler, Jaime

    2015-01-01

    Summary The precise regulation of cerebral blood flow is critical for normal brain function and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We found that capillary pericytes in mice and humans do not express smooth muscle actin and are morphologically and functionally distinct from adjacent precapillary smooth muscle cells (SMCs). Using optical imaging we investigated blood flow regulation at various sites on the vascular tree in living mice. Optogenetic, whisker stimulation or cortical spreading depolarization caused microvascular diameter or flow changes in SMC but not pericyte-covered microvessels. During early stages of brain ischemia, transient SMC but not pericyte constrictions were a major cause of hypoperfusion leading to thrombosis and distal microvascular occlusions. Thus, capillary pericytes are not contractile and regulation of cerebral blood flow in physiological and pathological conditions is mediated by arteriolar smooth muscle cells. PMID:26119027

  10. In Silico Neuro-Oncology: Brownian Motion-Based Mathematical Treatment as a Potential Platform for Modeling the Infiltration of Glioma Cells into Normal Brain Tissue.

    PubMed

    Antonopoulos, Markos; Stamatakos, Georgios

    2015-01-01

    Intensive glioma tumor infiltration into the surrounding normal brain tissues is one of the most critical causes of glioma treatment failure. To quantitatively understand and mathematically simulate this phenomenon, several diffusion-based mathematical models have appeared in the literature. The majority of them ignore the anisotropic character of diffusion of glioma cells since availability of pertinent truly exploitable tomographic imaging data is limited. Aiming at enriching the anisotropy-enhanced glioma model weaponry so as to increase the potential of exploiting available tomographic imaging data, we propose a Brownian motion-based mathematical analysis that could serve as the basis for a simulation model estimating the infiltration of glioblastoma cells into the surrounding brain tissue. The analysis is based on clinical observations and exploits diffusion tensor imaging (DTI) data. Numerical simulations and suggestions for further elaboration are provided. PMID:26309390

  11. Neural substrates for the processing of cognitive and affective aspects of taste in the brain.

    PubMed

    Yamamoto, Takashi

    2006-12-01

    Taste is unique among the sensory systems in that, besides its recognition of quality, it is innately associated with hedonic aspects of reward and aversion. This review of the literature will show how taste information is conveyed through the central gustatory pathways to the cortical gustatory area and is processed in terms of qualitative and quantitative aspects. Taste information is also sent to the reward system and feeding center via several brain sites including the prefrontal cortex, insular cortex, and amygdala. The reward system contains the ventral tegmental area, nucleus accumbens, and ventral pallidum; it finally sends information to the lateral hypothalamic area, the feeding center. The dopamine system originating from the ventral tegmental area mediates the motivation to consume palatable food. The actual ingestive behavior is promoted by the orexigenic neuropeptides from the hypothalamus. In the last section, the neural substrate of learning and memory of taste is introduced and the biological mechanisms are elucidated. PMID:17287579

  12. Infarct hemisphere and noninfarcted brain volumes affect locomotor performance following stroke

    PubMed Central

    Chen, I-Hsuan; Novak, Vera

    2014-01-01

    Objective: Brain damage within the right middle cerebral artery (MCA) territory is particularly disruptive to mediolateral postural stabilization. The objective of this cross-sectional study was to test the hypothesis that chronic right MCA infarcts (as compared to left) are associated with slower and more bilaterally asymmetrical gait. We further hypothesized that in those with chronic right MCA infarct, locomotor performance is more dependent on gray matter (GM) volumes within noninfarcted regions of the brain that are involved in motor control yet lie outside of the MCA territory. Methods: Gait speed was assessed in 19 subjects with right MCA infarct, 20 with left MCA infarct, and 108 controls. Bilateral plantar pressure and temporal symmetry ratios were calculated in a subset of the cohort. GM volumes within 5 regions outside of the MCA territory (superior parietal lobe, precuneus, caudate, putamen, and cerebellum) were quantified from anatomic MRIs. Results: Right and left infarct groups had similar poststroke duration (7.6 ± 6.0 years), infarct size, and functional independence. The right infarct group demonstrated slower gait speed and greater asymmetry compared to the left infarct group and controls (p < 0.05). In the right infarct group only, those with larger GM volumes within the cerebellum (r2 = 0.32, p = 0.02) and caudate (r2 = 0.56, p < 0.001) exhibited faster gait speed. Conclusion: Individuals with chronic lesions within the right MCA territory, as compared to the left MCA territory, exhibit slower, more asymmetrical gait. For these individuals, larger GM volumes within regions outside of the infarcted vascular territory may help preserve locomotor control. PMID:24489132

  13. 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 from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. PMID:27317610

  14. Two types of mental fatigue affect spontaneous oscillatory brain activities in different ways

    PubMed Central

    2013-01-01

    Background Fatigue has a multi-factorial nature. We examined the effects of two types of mental fatigue on spontaneous oscillatory brain activity using magnetoencephalography (MEG). Methods Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of a 30-min fatigue-inducing 0- or 2-back test session and two evaluation sessions performed just before and after the fatigue-inducing mental task session. Results After the 0-back test, decreased alpha power was indicated in the right angular gyrus and increased levels in the left middle and superior temporal gyrus, left postcentral gyrus, right superior frontal gyrus, left inferior frontal gyrus, and right medial frontal gyrus. After the 2-back test, decreased alpha power was indica