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Sample records for abnormal brain aging

  1. N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.

    Science.gov (United States)

    Sabayan, Behnam; van Buchem, Mark A; de Craen, Anton J M; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2015-09-01

    To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. © 2015 American Academy of Neurology.

  2. Positron emission tomography studies in the normal and abnormal ageing of human brain

    International Nuclear Information System (INIS)

    Comar, D.; Baron, J.C.

    1987-01-01

    Until recently, the investigation of the neurophysiological correlates of normal and abnormal ageing of the human brain was limited by methodological constraints, as the technics available provided only a few parameters (e.g. electroencephalograms, cerebral blood flow) monitored in superficial brain structures in a grossly regional and poorly quantitative way. Lately several non invasive techniques have been developed which allow to investigate in vivo both quantitatively and on local basis a number of previously inaccessible important aspects of brain function. Among these techniques, such as single photon emission tomography imaging of computerized electric events, nuclear magnetic resonance, positron emission tomography stands out as the most powerful and promising method since it allows the in vivo measurement of biochemical and pharmacological parameters

  3. Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics.

    Science.gov (United States)

    Kou, Xianjuan; Li, Jie; Liu, Xingran; Chang, Jingru; Zhao, Qingxia; Jia, Shaohui; Fan, Jingjing; Chen, Ning

    2017-06-01

    microRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. To explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with d-galactose (d-gal)-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of d-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics. Meanwhile, whether the upregulation of miR-34a can lead to dysfunctional autophagy and abnormal mitochondrial dynamics was confirmed in human SH-SY5Y cells with silenced miR-34a by the transfection of a miR-34a inhibitor. Results indicated that swimming intervention could significantly attenuate cognitive impairment, prevent the upregulation of miR-34a, mitigate the dysfunctional autophagy, and inhibit the increase of dynamin-related protein 1 (DRP1) in d-gal-induced aging model rats. In contrast, the miR-34a inhibitor in cell model not only attenuated D-gal-induced the impairment of autophagy but also decreased the expression of DRP1 and mitofusin 2 (MFN2). Therefore, swimming training can delay brain aging of d-gal-induced aging rats through attenuating the impairment of miR-34a-mediated autophagy and abnormal mitochondrial dynamics, and miR-34a could be the novel therapeutic target for aging-related diseases such as AD. NEW & NOTEWORTHY In the present study, we have found that the upregulation of miR-34a is the hallmark of aging or aging-related diseases, which can result in dysfunctional autophagy and abnormal mitochondrial dynamics. In contrast, swimming intervention can delay the aging process by rescuing the impaired functional status of autophagy and abnormal mitochondrial dynamics via the suppression of miR-34a. Copyright © 2017 the American Physiological Society.

  4. Aging Brain, Aging Mind.

    Science.gov (United States)

    Selkoe, Dennis J.

    1992-01-01

    Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

  5. Brain and bone abnormalities of thanatophoric dwarfism.

    Science.gov (United States)

    Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa

    2009-01-01

    The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.

  6. Cognition and brain functional aging

    Directory of Open Access Journals (Sweden)

    Hui-jie LI

    2014-03-01

    Full Text Available China has the largest population of elderly adults. Meanwhile, it is one of the countries showing fastest aging speed in the world. Aging processing is always companied with a series of brain structural and functional changes, which result in the decline of processing speed, working memory, long-term memory and executive function, etc. The studies based on functional magnetic resonance imaging (fMRI found certain aging effects on brain function activation, spontaneous activity and functional connectivity in old people. However, few studies have explored the brain functional curve during the aging process while most previous studies explored the differences in the brain function between young people and old people. Delineation of the human brain functional aging curve will promote the understanding of brain aging mechanisms and support the normal aging monitoring and early detection of abnormal aging changes. doi: 10.3969/j.issn.1672-6731.2014.03.005

  7. [Patterns of brain ageing].

    Science.gov (United States)

    Fernández Viadero, Carlos; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

    2017-06-01

    Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and β-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Outcome prediction in mild traumatic brain injury: age and clinical variables are stronger predictors than CT abnormalities.

    NARCIS (Netherlands)

    Jacobs, B.; Beems, T.; Stulemeijer, M.; Vugt, A.B. van; Vliet, A.M. van der; Borm, G.F.; Vos, P.E.

    2010-01-01

    Mild traumatic brain injury (mTBI) is a common heterogeneous neurological disorder with a wide range of possible clinical outcomes. Accurate prediction of outcome is desirable for optimal treatment. This study aimed both to identify the demographic, clinical, and computed tomographic (CT)

  9. Migraine and structural abnormalities in the brain

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, Faisal Mohammad; Ashina, Messoud

    2014-01-01

    PURPOSE OF REVIEW: The aim is to provide an overview of recent studies of structural brain abnormalities in migraine and to discuss the potential clinical significance of their findings. RECENT FINDINGS: Brain structure continues to be a topic of extensive research in migraine. Despite advances...... in neuroimaging techniques, it is not yet clear if migraine is associated with grey matter changes. Recent large population-based studies sustain the notion of increased prevalence of white matter abnormalities in migraine, and possibly of silent infarct-like lesions. The clinical relevance of this association...

  10. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Woojun Kim

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD, and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.

  11. Brain abnormalities in murderers indicated by positron emission tomography.

    Science.gov (United States)

    Raine, A; Buchsbaum, M; LaCasse, L

    1997-09-15

    Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

  12. Brain MRI abnormalities in neuromyelitis optica

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    Wang Fei, E-mail: feiwang1973@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Liu Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Duan Yunyun, E-mail: duanyun2003@sohu.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Li Kuncheng, E-mail: kunchengli@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Education Ministry Key Laboratory for Neurodegenerative Disease, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China)

    2011-11-15

    Objective: The purpose of this study was to explore brain MRI findings in neuromyelitis optica (NMO) and to investigate specific brain lesions with respect to the localization of aquaporin-4 (AQP-4). Materials and methods: Forty admitted patients (36 women) who satisfied the 2006 criteria of Wingerchuk et al. for NMO were included in this study. All patients received a neurological examination and MRI scanning including brain and spinal cord. MRIs were classified as normal, nonspecific, multiple sclerosis-like, typical abnormalities. MS-like lesions were too few to satisfy the Barkhof et al. criteria for MS. Confluent lesions involving high AQP-4 regions were considered typical. Non-enhancing deep white matter lesions other than MS-like lesions or typical lesions were classified as nonspecific. Results: Brain MRI lesions were delineated in 12 patients (25%). Four patients (10%) had hypothalamus, brainstem or periventricle lesions. Six (15%) patients were nonspecific, and 2 (5%) patients had multiple sclerosis-like lesions. Conclusion: Brain MRIs are negative in most NMO, and brain lesions do not exclude the diagnosis of NMO. Hypothalamus, brainstem or periventricle lesions, corresponding to high sites of AQP-4 in the brain, are indicative of lesions of NMO.

  13. Brain MRI abnormalities in neuromyelitis optica

    International Nuclear Information System (INIS)

    Wang Fei; Liu Yaou; Duan Yunyun; Li Kuncheng

    2011-01-01

    Objective: The purpose of this study was to explore brain MRI findings in neuromyelitis optica (NMO) and to investigate specific brain lesions with respect to the localization of aquaporin-4 (AQP-4). Materials and methods: Forty admitted patients (36 women) who satisfied the 2006 criteria of Wingerchuk et al. for NMO were included in this study. All patients received a neurological examination and MRI scanning including brain and spinal cord. MRIs were classified as normal, nonspecific, multiple sclerosis-like, typical abnormalities. MS-like lesions were too few to satisfy the Barkhof et al. criteria for MS. Confluent lesions involving high AQP-4 regions were considered typical. Non-enhancing deep white matter lesions other than MS-like lesions or typical lesions were classified as nonspecific. Results: Brain MRI lesions were delineated in 12 patients (25%). Four patients (10%) had hypothalamus, brainstem or periventricle lesions. Six (15%) patients were nonspecific, and 2 (5%) patients had multiple sclerosis-like lesions. Conclusion: Brain MRIs are negative in most NMO, and brain lesions do not exclude the diagnosis of NMO. Hypothalamus, brainstem or periventricle lesions, corresponding to high sites of AQP-4 in the brain, are indicative of lesions of NMO.

  14. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Takeda, Shumpei; Hatazawa, Jun

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT and following results were obtained. Brain atrophy was minimal in 34 -- 35 years old in both sexes, increased exponentially to the increasing age after 34 -- 35 years, and probably resulted in dementia, such as vascular or multiinfarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34 -- 35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extents of brain atrophy (20 -- 30 %) existed among aged subjects. Some aged subjects had little or no atrophy of their brains, as seen in young subjects, and others had markedly shrunken brains associated with senility. From these results there must be pathological factors promoting brain atrophy with a great individual difference. We have studied the relation of intelligence to brain volume, and have ascertained that progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was decrease in the cerebral blood flow. MNR-CT can easily detected small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy, while X-CT can not. Therefore NMR-CT is very useful for detection of subtle changes in the brain. (J.P.N.)

  15. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Yamada, Kenji; Yamada, Susumu; Ono, Shuichi; Takeda, Shunpei; Hatazawa, Jun; Ito, Masatoshi; Kubota, Kazuo

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  16. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, W F C; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder......, delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed...

  17. Structural brain abnormalities in Cushing's syndrome.

    Science.gov (United States)

    Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

    2018-05-08

    Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

  18. Imaging findings of the brain abnormalities in acute lymphoblastic leukemia of children during and after treatment

    International Nuclear Information System (INIS)

    Lee, Kyung Joo; Lee, Seung Rho; Park, Dong Woo; Joo, Kyung Bin; Kim, Jang Wook; Hahm, Chang Kok; Kim, Ki Joong; Lee, Hahng

    2001-01-01

    We evaluated the imaging abnormalities of the brain observed during and after treatment of acute childhood lymphoblastic leukemia. The study group consisted of 30 patients (male : female=19 : 11 ; mean age, 64 months) with acute childhood lymphoblastic leukemia during the previous ten-year period who had undergone prophylaxis of the central nervous system. Irrespective of the CNS symptoms, base-line study of the brain involving CT and follow-up CT or MRI was undertaken more than once. We retrospectively evaluated the imaging findings, methods of treatment, associated CNS symptoms, and the interval between diagnosis and the time at which brain abnormalities were revealed by imaging studies. In 15 (50% ; male : female=9 : 6 ; mean age, 77 months) of 30 patients, brain abnormalities that included brain atrophy (n=9), cerebral infarctions (n=4), intracranial hemorrhage (n=1), mineralizing microangiopathy (n=2), and periventricular leukomalacia (n=3) were seen on follow-up CT or MR images. In four of nine patients with brain atrophy, imaging abnormalities such as periventricular leukomalacia (n=2), infarction (n=1) and microangiopathy (n=1) were demonstrated. Fourteen of the 15 patients underwent similar treatment ; the one excluded had leukemic cells in the CSF. Six patients had CNS symptoms. In the 15 patients with abnormal brain imaging findings, the interval between diagnosis and the demonstration of brain abnormalities was between one month and four years. After the cessation of treatment, imaging abnormalities remained in all patients except one with brain atrophy. Various imaging abnormalities of the brain may be seen during and after the treatment of acute childhood lymphoblastic leukemia and persist for a long time. In children with this condition, the assessment of brain abnormalities requires follow-up study of the brain

  19. Imaging findings of the brain abnormalities in acute lymphoblastic leukemia of children during and after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Joo; Lee, Seung Rho; Park, Dong Woo; Joo, Kyung Bin; Kim, Jang Wook; Hahm, Chang Kok; Kim, Ki Joong; Lee, Hahng [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

    2001-09-01

    We evaluated the imaging abnormalities of the brain observed during and after treatment of acute childhood lymphoblastic leukemia. The study group consisted of 30 patients (male : female=19 : 11 ; mean age, 64 months) with acute childhood lymphoblastic leukemia during the previous ten-year period who had undergone prophylaxis of the central nervous system. Irrespective of the CNS symptoms, base-line study of the brain involving CT and follow-up CT or MRI was undertaken more than once. We retrospectively evaluated the imaging findings, methods of treatment, associated CNS symptoms, and the interval between diagnosis and the time at which brain abnormalities were revealed by imaging studies. In 15 (50% ; male : female=9 : 6 ; mean age, 77 months) of 30 patients, brain abnormalities that included brain atrophy (n=9), cerebral infarctions (n=4), intracranial hemorrhage (n=1), mineralizing microangiopathy (n=2), and periventricular leukomalacia (n=3) were seen on follow-up CT or MR images. In four of nine patients with brain atrophy, imaging abnormalities such as periventricular leukomalacia (n=2), infarction (n=1) and microangiopathy (n=1) were demonstrated. Fourteen of the 15 patients underwent similar treatment ; the one excluded had leukemic cells in the CSF. Six patients had CNS symptoms. In the 15 patients with abnormal brain imaging findings, the interval between diagnosis and the demonstration of brain abnormalities was between one month and four years. After the cessation of treatment, imaging abnormalities remained in all patients except one with brain atrophy. Various imaging abnormalities of the brain may be seen during and after the treatment of acute childhood lymphoblastic leukemia and persist for a long time. In children with this condition, the assessment of brain abnormalities requires follow-up study of the brain.

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

    Science.gov (United States)

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

    2005-09-01

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

  1. Initial brain aging

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB(m/m)) and C57Bl/6 (WT......) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB(m/m) hippocampus, but not in CSB(m/m) cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased....... Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB(m/m) compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event...

  2. Insulin and brain aging

    OpenAIRE

    Baranowska-Bik, Agnieszka; Bik, Wojciech

    2017-01-01

    The world’s population is living much longer than in the past. It is crucial to find as many pathological factors that deteriorate the health condition and well-being of elderly people as possible. Loss of activity and functions over time is typical for elderly people. Aging affects brain function, metabolism and structure in different ways, and these effects have multiple etiologies. Cognitive impairment, impaired neurotransmitter activity and reduction of brain volume are observed in th...

  3. Brain perfusion abnormalities in patients with euthyroid autoimmune thyroiditis

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    Piga, M.; Serra, A.; Loi, G.L.; Satta, L. [University of Cagliari, Nuclear Medicine - Department of Medical Sciences ' ' M. Aresu' ' , Cagliari (Italy); Deiana, L.; Liberto, M. Di; Mariotti, S. [University of Cagliari, Endocrinology - Department of Medical Sciences ' ' M. Aresu' ' , Cagliari (Italy)

    2004-12-01

    Brain perfusion abnormalities have recently been demonstrated by single-photon emission computed tomography (SPECT) in rare cases of severe Hashimoto's thyroiditis (HT) encephalopathy; moreover, some degree of subtle central nervous system (CNS) involvement has been hypothesised in HT, but no direct evidence has been provided so far. The aim of this study was to assess cortical brain perfusion in patients with euthyroid HT without any clinical evidence of CNS involvement by means of {sup 99m}Tc-ECD brain SPECT. Sixteen adult patients with HT entered this study following informed consent. The diagnosis was based on the coexistence of high titres of anti-thyroid auto-antibodies and diffuse hypoechogenicity of the thyroid on ultrasound in association with normal circulating thyroid hormone and TSH concentrations. Nine consecutive adult patients with non-toxic nodular goitre (NTNG) and ten healthy subjects matched for age and sex were included as control groups. All patients underwent {sup 99m}Tc-ECD brain SPECT. Image assessment was both qualitative and semiquantitative. Semiquantitative analysis was performed by generation of four regions of interest (ROI) for each cerebral hemisphere - frontal, temporal, parietal and occipital - and one for each cerebellar hemisphere in order to evaluate cortical perfusion asymmetry. The Asymmetry Index (AI) was calculated to provide a measurement of both magnitude and direction of perfusion asymmetry. As assessed by visual examination, {sup 99m}Tc-ECD cerebral distribution was irregular and patchy in HT patients, hypoperfusion being more frequently found in frontal lobes. AI revealed abnormalities in 12/16 HT patients, in three of the nine NTNG patients and in none of the normal controls. A significant difference in the mean AI was found between patients with HT and both patients with NTNG (p<0.003) and normal controls (p<0.001), when only frontal lobes were considered. These results show the high prevalence of brain perfusion

  4. Cognition and brain abnormalities on MRI in pituitary patients

    Energy Technology Data Exchange (ETDEWEB)

    Brummelman, Pauline [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Sattler, Margriet G.A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Meiners, Linda C. [Department of Radiology, University of Groningen, University Medical Center Groningen (Netherlands); Berg, Gerrit van den; Klauw, Melanie M. van der [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Elderson, Martin F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Dullaart, Robin P.F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Koerts, Janneke [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Werumeus Buning, Jorien, E-mail: j.werumeus.buning@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Tucha, Oliver [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Bergh, Alfons C.M. van den [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Beek, André P. van, E-mail: a.p.van.beek@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands)

    2015-02-15

    Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

  5. Cognition and brain abnormalities on MRI in pituitary patients

    International Nuclear Information System (INIS)

    Brummelman, Pauline; Sattler, Margriet G.A.; Meiners, Linda C.; Berg, Gerrit van den; Klauw, Melanie M. van der; Elderson, Martin F.; Dullaart, Robin P.F.; Koerts, Janneke; Werumeus Buning, Jorien; Tucha, Oliver; Wolffenbuttel, Bruce H.R.; Bergh, Alfons C.M. van den; Beek, André P. van

    2015-01-01

    Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

  6. Normal and abnormal aging in bilinguals

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila

    Full Text Available Abstract Bilinguals use two different language systems to mediate not only social communication, but also cognitive processes. Potential differences between bilinguals and monolinguals in task-solving strategies and patterns of cognitive decline during normal and abnormal aging have been suggested. Main contribution: A research review of the area suggests that normal aging is associated with increased interference between the two languages and tendency to retreat to a single language. General cognitive functioning has been found to be higher in demented bilingual patients if communication is carried out in L1 rather than in L2. Recent research has reported that bilingualism can have a protective effect during aging, attenuating the normal cognitive decline associated with aging, and delaying the onset of dementia. Conclusions: Regardless of the significant heterogeneity of bilingualism and the diversity of patterns in language use during life-span, current research suggests that bilingualism is associated with preserved cognitive test performance during aging, and potentially can have some protective effect in dementia.

  7. Abnormal glutamate release in aged BTBR mouse model of autism.

    Science.gov (United States)

    Wei, Hongen; Ding, Caiyun; Jin, Guorong; Yin, Haizhen; Liu, Jianrong; Hu, Fengyun

    2015-01-01

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses between the BTBR mice with low level sociability and B6 mice with high level sociability. The results revealed that the number of excitatory synapse colocalized with pre- and post-synaptic marker was not different between aged BTBR and B6 mice. The aged BTBR mice had a normal structure of dendritic spine and the expression of Shank3 protein in the brain as well as that in B6 mice. The baseline and KCl-evoked glutamate release from the cortical synaptoneurosome in aged BTBR mice was lower than that in aged B6 mice. Overall, the data indicate that there is a link between disturbances of the glutamate transmission and autism. These findings provide new evidences for the hypothesis of excitation/inhibition imbalance in autism. Further work is required to determine the cause of this putative abnormality.

  8. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza

    2015-01-01

    , the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  9. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

    OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A

  10. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H.; Underwood, Jonathan; Caan, Matthan W. A.; de Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W. N. M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B. L. M.; Winston, Alan; Reiss, Peter; Sharp, David J.; Schouten, J.; Kooij, K. W.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Schrijver, J. H. N.; Zikkenheiner, W.; van der Valk, M.; Henderiks, A.; Kootstra, N. A.; Harskamp-Holwerda, A. M.; Maurer, I.; Ruiz, M. M. Mangas; Booiman, T.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Stege, J. A. ter; Twennaar, M. Klein; Su, T.; Siteur-van Rijnstra, E.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé , H. G.; Tembo, L.; Stott, M.; Prins, M. [= Maria

    2017-01-01

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of

  11. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    International Nuclear Information System (INIS)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi

    1994-01-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author)

  12. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi (Kyoto Prefectural Univ. of Medicine (Japan))

    1994-11-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author).

  13. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    Science.gov (United States)

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  14. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    Science.gov (United States)

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

  15. A family affair: brain abnormalities in siblings of patients with schizophrenia

    Science.gov (United States)

    Hulshoff Pol, Hilleke; Gogtay, Nitin

    2013-01-01

    Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development. PMID:23698280

  16. Brain aging and therapeutic interventions

    DEFF Research Database (Denmark)

    This book brings together most up-to-date information on different aspects of brain aging and on the strategies for intervention and therapy of age-related brain disorders. It includes 18 chapters by leading researchers, and each chapter is a comprehensive and critical review of the topic...

  17. Nutrients, Microglia Aging, and Brain Aging

    Directory of Open Access Journals (Sweden)

    Zhou Wu

    2016-01-01

    Full Text Available As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  18. Nutrients, Microglia Aging, and Brain Aging.

    Science.gov (United States)

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  19. Abnormal rich club organization and functional brain dynamics in schizophrenia.

    Science.gov (United States)

    van den Heuvel, Martijn P; Sporns, Olaf; Collin, Guusje; Scheewe, Thomas; Mandl, René C W; Cahn, Wiepke; Goñi, Joaquín; Hulshoff Pol, Hilleke E; Kahn, René S

    2013-08-01

    The human brain forms a large-scale structural network of regions and interregional pathways. Recent studies have reported the existence of a selective set of highly central and interconnected hub regions that may play a crucial role in the brain's integrative processes, together forming a central backbone for global brain communication. Abnormal brain connectivity may have a key role in the pathophysiology of schizophrenia. To examine the structure of the rich club in schizophrenia and its role in global functional brain dynamics. Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in patients with schizophrenia and matched healthy controls. Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. Forty-eight patients and 45 healthy controls participated in the study. An independent replication data set of 41 patients and 51 healthy controls was included to replicate and validate significant findings. MAIN OUTCOME(S) AND MEASURES: Measures of rich club organization, connectivity density of rich club connections and connections linking peripheral regions to brain hubs, measures of global brain network efficiency, and measures of coupling between brain structure and functional dynamics. Rich club organization between high-degree hub nodes was significantly affected in patients, together with a reduced density of rich club connections predominantly comprising the white matter pathways that link the midline frontal, parietal, and insular hub regions. This reduction in rich club density was found to be associated with lower levels of global communication capacity, a relationship that was absent for other white matter pathways. In addition, patients had an increase in the strength of structural connectivity-functional connectivity coupling. Our findings provide novel biological evidence that schizophrenia is characterized by a selective

  20. Effects of smoking on brain aging, 2

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Matsuzawa, Taiju; Fujiwara, Takehiko

    1985-01-01

    Brain atrophy during normal aging and its relation to chronic smoking was studied using quantitative volumetric measurements of computed tomography. Study was performed about 159 smokers and 194 non-smokers with no neurological abnormality nor focal abnormality in CT scans. Each pixel of head CT scans was computed and Brain Volume Index (BVI) was calculated. BVI showed a significant decrease in smokers compared to non-smokers in three age groups, 50-to-54, 55-to-59 (p < 0.001, both) and 65-to-69 (p < 0.05). A dose-response study in the male showed that BVI in smokers was significantly lower than that for non smokers. Mean BVI tended to decrease when the smoking index increased but the trend was not significant. The systolic blood pressure and serum triglycrides of smokers were significantly higher than non-smokers (p < 0.002 and p < 0.05). It was suggested that age-related brain atrophy was enhanced by chronic smoking. Previously we showed that cerebral blood flow (CBF) was significantly lower in smokers than in non-smokers. Then, we suggest the following hypothesis; smoking chronically advances atherosclerosis, both atherosclerosis and high blood pressure reduce CBF, reduced CBF accelerated the lose of neurons which finally renders the brain atrophic. (author)

  1. Neurogenesis in the aging brain.

    Science.gov (United States)

    Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

    2017-10-01

    Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Hypomelanosis of Ito and brain abnormalities: MRI findings and literature review

    International Nuclear Information System (INIS)

    Steiner, J.; Adamsbaum, C.; Desguerres, I.; Lalande, G.; Raynaud, F.; Ponsot, G.; Kalifa, G.

    1996-01-01

    We report the results of a 14-year retrospective study of brain MRI abnormalities in 12 pediatric patients presenting with hypomelanosis of Ito (HI). Miscellaneous brain abnormalities were found: one patient had a medulloblastoma, three had cortical malformations, and five demonstrated ''minor'' abnormalities such as dilated Virchow-Robin spaces or brain atrophy. We emphasize the polymorphism of brain abnormalities associated with HI. (orig.). With 5 figs., 1 tab

  3. SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury.

    Science.gov (United States)

    Abdel-Dayem, H M; Abu-Judeh, H; Kumar, M; Atay, S; Naddaf, S; El-Zeftawy, H; Luo, J Q

    1998-05-01

    The purpose of this atlas is to present a review of the literature showing the advantages of SPECT brain perfusion imaging (BPI) in mild or moderate traumatic brain injury (TBI) over other morphologic imaging modalities such as x-ray CT or MRI. The authors also present the technical recommendations for SPECT brain perfusion currently practiced at their center. For the radiopharmaceutical of choice, a comparison between early and delayed images using Tc-99m HMPAO and Tc-99m ECD showed that Tc-99m HMPAO is more stable in the brain with no washout over time. Therefore, the authors feel that Tc-99m HMPAO is preferable to Tc-99m ECD. Recommendations regarding standardizing intravenous injection, the acquisition, processing parameters, and interpretation of scans using a ten grade color scale, and use of the cerebellum as the reference organ are presented. SPECT images of 228 patients (age range, 11 to 88; mean, 40.8 years) with mild or moderate TBI and no significant medical history that interfered with the results of the SPECT BP were reviewed. The etiology of the trauma was in the following order of frequency: motor vehicle accidents (45%) followed by blow to the head (36%) and a fall (19%). Frequency of the symptoms was headache (60.9%), memory problems (27.6%), dizziness (26.7%), and sleep disorders (8.7%). Comparison between patients imaged early (3 months) from the time of the accident, showed that early imaging detected more lesions (4.2 abnormal lesions per study compared to 2.7 in those imaged more than 3 months after the accident). Of 41 patients who had mild traumatic injury without loss of consciousness and had normal CT, 28 studies were abnormal. Focal areas of hypoperfusion were seen in 77% (176 patients, 612 lesions) of the group of 228 patients. The sites of abnormalities were in the following order: basal ganglia and thalami, 55.2%, frontal lobes, 23.8%, temporal lobes, 13%, parietal, 3.7%, insular and occipital lobes together, 4.6%.

  4. Aging, Brain Size, and IQ.

    Science.gov (United States)

    Bigler, Erin D.; And Others

    1995-01-01

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

  5. Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

    Science.gov (United States)

    Hotta, Jaakko; Saari, Jukka; Koskinen, Miika; Hlushchuk, Yevhen; Forss, Nina; Hari, Riitta

    2017-03-01

    Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q frontal gyrus, secondary somatosensory cortex, inferior parietal lobule, orbitofrontal cortex, and thalamus. Our findings indicate that CRPS impairs action observation by affecting brain areas related to pain processing and motor control. This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Increased brain-predicted aging in treated HIV disease.

    Science.gov (United States)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

    2017-04-04

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  7. Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

    Science.gov (United States)

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

  8. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE....... Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829....... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...

  9. Biology of aging brain

    Directory of Open Access Journals (Sweden)

    Shankar S

    2010-10-01

    Full Text Available Normal aging of the nervous system is associated with some degree of decline in a number of cognitive functions. With the present day attempts to increase the life span, understanding the metabolic interactions and various mechanisms involved in normal neuronal aging continues to be a challenge. Loss of neurons is now recognized to be more modest than the initial estimates suggested and the loss only affected some of the specific neuroanatomical areas like hippocampus and prefrontal cortex. Individual neurons in addition show reduced size of dendritic and axonal arborization. Neurons have significant homeostatic control of the essential physiological functions like synaptic excitability, gene expression and metabolic regulation. Deviation in these normal events can have severe consequences as observed in aging and neurodegeneration. Based on experimental evidence, the evolution of aging is probably the result of altered metabolic triad: the mitochondria, reactive oxygen species and intracellular calcium homeostasis. Perturbations in the metabolic and functional state of this triad lead to a state of decreased homeostatic reserve, where the aged neurons still could maintain adequate function during normal activity. However, these neurons become vulnerable to the stress of excessive metabolic loads associated with spells of ischemia, trauma progressing to neuronal degeneration. Age-related neuronal dysfunction probably involves a host of subtle changes involving the synapses, receptors, neurotransmitters, cytological alterations, electrical transmission, leading to cognitive dysfunction. An exaggeration of it could be the clinical manifestation of dementia, with intraneuronal accumulation of protein aggregates deranging the metabolic state. This review deals with some of the structural, functional and metabolic features of aging nervous system and discusses briefly the functional consequences.

  10. Aging of the Brain: How Can We Prevent It?

    Science.gov (United States)

    Jarvik, Lissy F.

    1988-01-01

    Contends distinction between normal and abnormal aging of the brain changes as data emerge which identify as pathology what had previously been considered the norm. Reviews research on effects of aging in twins begun in 1940s, focusing on facts related to intellectual decline, neuropsychological test performance relationship to dementia, and…

  11. Abnormal lung function at preschool age asthma in adolescence?

    Science.gov (United States)

    Lajunen, Katariina; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Sarna, Seppo; Malmberg, L Pekka; Pelkonen, Anna S; Mäkelä, Mika J

    2018-05-01

    Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. MRI abnormalities and related risk factors of the brain in patients with neuromyelitis optica

    International Nuclear Information System (INIS)

    Xiao Hui; Ma Lin; Lou Xin; Cai Youquan; Wang Yulin; Wang Yan; Wu Lei; Wu Weiping

    2011-01-01

    Objective: To investigate the MRI features of the brain in patients with neuromyelitis optica (NMO), and to evaluate the correlation between the brain abnormalities and related risk factors. Methods: Fifty-four patients with definite NMO according to 2006 Wingerchuk diagnosis criteria were enrolled in this study. MRI scanning of the brain was performed in these patients. Distribution and signal features of all the lesions were analyzed. A Logistic regression analysis was used to evaluate the risk factors of brain abnormalities. Results: Twenty-four NMO patients (44.4%) showed unremarkable findings and thirty (55.6%) showed abnormalities on brain MRI. Multiple and non-specific small lesions in the subcortical white matter and grey-white matter junction were the most frequent abnormalities on brain MRI (13/30, 43.3%). Typical lesion locations included corpus callosum, subependyma of ventricles, hypothalamus and brain stem. The lesions showed punctate, patchy and linear abnormal signals. Post-contrast MRI showed no abnormal enhancement in 16 cases. Logistic regression analysis showed that coexisting autoimmune disease or infection. history had correlations with abnormalities of the brain on MRI (OR=3.519, P<0.05). Conclusions: There was a high incidence of brain abnormalities in NMO. Subependymal white matter, corpus callosum, hypothalamus and brain stem were often involved in NMO. NMO patients with coexisting autoimmune disease and infection history had higher risk of brain abnormalities. (authors)

  13. Specificity of abnormal brain volume in major depressive disorder: a comparison with borderline personality disorder.

    Science.gov (United States)

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Thomann, Philipp A; Christian Wolf, R

    2015-03-15

    Abnormal brain volume has been frequently demonstrated in major depressive disorder (MDD). It is unclear if these findings are specific for MDD since aberrant brain structure is also present in disorders with depressive comorbidity and affective dysregulation, such as borderline personality disorder (BPD). In this transdiagnostic study, we aimed to investigate if regional brain volume loss differentiates between MDD and BPD. Further, we tested for associations between brain volume and clinical variables within and between diagnostic groups. 22 Females with a DSM-IV diagnosis of MDD, 17 females with a DSM-IV diagnosis of BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls (HC) were investigated using magnetic resonance imaging. High-resolution structural data were analyzed using voxel-based morphometry. A significant (pdisorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Paediatrics brain imaging in epilepsy: common presenting symptoms and spectrum of abnormalities detected on MRI

    International Nuclear Information System (INIS)

    Ali, A.; Akram, F.; Khan, G.; Hussain, S.

    2017-01-01

    Epilepsy, a common neurological disorder can present at any age and has a number of aetiologies with underlying brain disease being the most common aetiology. Brain imaging becomes important and mandatory in the work up for epilepsy in localization and lateralization of the seizure focus. Methods: This cross-sectional study was conducted in the department of Radiology Ayub Medical Teaching Institution Abbottabad from 1st March 2015 to 31st March 2016. A total of 209 children aged 28 days to 14 years were included in the study who presented with seizures to clinicians. Information obtained from history, clinical examination and investigations especially MRI brains were recorded in a prescribed pro forma. The data was analysed in SPSS 20. Results: MRI examination was unremarkable in 44.01% (n=92) and mild generalized brain atrophy was noted in 12.91% (n=27). Arachnoid cysts, mild unilateral brain atrophy and hydrocephalous due to aqueduct stenosis were recorded in 3.82% (n=8) of each group. Neoplastic lesions were the second most common abnormal MRI finding and constituted 5.74% (n=12). Leukodystrophy was diagnosed in 4.78% (n=10). MRI examination showed ring enhancing lesions (tuberculomas) and AVM in 1.43% (n=3) of each group. Perinatal ischemia and intracranial infection, (focal or generalized) were recorded in 2.87% (n=6) of each group. A 0.95 % (n=2) of children in each group had agenesis of corpus callosum and cavernoma. The radiological MRI diagnosis of Raussmussen encephalitis was made in 3.34% (n=7). Single case, each of mesial temporal sclerosis, subdural haemorrhage, infarct and craniopharyngioma was recorded making 0.47 % of the total patients in each case. Conclusion: MRI examination was abnormal in significant number of patients (55.86%), so therefore if properly utilized, in a good clinical context, this can identify most of the structural brain abnormalities in paediatric patients presenting with seizures. (author)

  15. Brain trace elements and aging

    International Nuclear Information System (INIS)

    Hebbrecht, Geert; Maenhaut, Willy; Reuck, Jacques de

    1999-01-01

    Degenerative mechanisms involved in the aging process of the brain are to a certain extent counteracted by repair mechanisms. In both degenerative and recovery processes, trace elements are involved. The present study focused on the role of two minor (i.e., K and Ca) and six trace elements (i.e., Mn, Fe, Cu, Zn, Se and Rb) in the aging process. The elements were determined by PIXE in cerebral cortex and white matter, basal ganglia, brainstem and cerebellar cortex of 18 postmortem human brains, from persons without a history of neurologic or psychiatric disease who deceased between the age of 7 and 79. This age range allowed us to study the relationship between elemental concentrations and age. The most prominent findings were a concentration decrease for K and Rb and a concentration increase for the elements Ca, Fe, Zn and Se. The study supports recent findings that Ca and Fe are involved in brain degenerative processes initiated by oxygen free radicals, whereas Zn and Se are involved in immunological reactions counteracting the aging process

  16. Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2017-03-01

    Full Text Available Background: Autism spectrum disorder (ASD, tic disorder (TD, and hyperkinetic syndrome of childhood (attention deficit disorder [ADD]/attention deficit hyperactivity disorder [ADHD] are disorders recently defined as abnormal connectivity spectrum disorders (ACSDs because they show a similar pattern of abnormal brain connectivity. This study examines whether these disorders are associated with exposure to thimerosal, a mercury (Hg-based preservative. Methods: A hypothesis testing case-control study evaluated the Vaccine Safety Datalink for the potential dose-dependent odds ratios (ORs for diagnoses of ASD, TD, and ADD/ADHD compared to controls, following exposure to Hg from thimerosal-containing Haemophilus influenzae type b vaccines administrated within the first 15 months of life. Febrile seizures, cerebral degeneration, and unspecified disorders of metabolism, which are not biologically plausibly linked to thimerosal, were examined as control outcomes. Results: On a per 25 μg Hg basis, cases diagnosed with ASD (OR = 1.493, TD (OR = 1.428, or ADD/ADHD (OR = 1.503 were significantly (P < .001 more likely than controls to have received increased Hg exposure. Similar relationships were observed when separated by gender. Cases diagnosed with control outcomes were no more likely than controls to have received increased Hg exposure. Conclusion: The results suggest that Hg exposure from thimerosal is significantly associated with the ACSDs of ASD, TD, and ADD/ADHD.

  17. Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses.

    Science.gov (United States)

    Chen, Vincent Chin-Hung; Shen, Chao-Yu; Liang, Sophie Hsin-Yi; Li, Zhen-Hui; Tyan, Yeu-Sheng; Liao, Yin-To; Huang, Yin-Chen; Lee, Yena; McIntyre, Roger S; Weng, Jun-Cheng

    2016-11-15

    It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits. The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS). Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (pdisorder with abnormal circuit structure and connectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Regional homogeneity of resting-state brain abnormalities in bipolar and unipolar depression.

    Science.gov (United States)

    Liu, Chun-Hong; Ma, Xin; Wu, Xia; Zhang, Yu; Zhou, Fu-Chun; Li, Feng; Tie, Chang-Le; Dong, Jie; Wang, Yong-Jun; Yang, Zhi; Wang, Chuan-Yue

    2013-03-05

    Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression (UD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right

  19. Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers

    NARCIS (Netherlands)

    van Zoest, Rosan A.; Underwood, Jonathan; de Francesco, Davide; Sabin, Caroline A.; Cole, James H.; Wit, Ferdinand W.; Caan, Matthan W. A.; Kootstra, Neeltje A.; Fuchs, Dietmar; Zetterberg, Henrik; Majoie, Charles B. L. M.; Portegies, Peter; Winston, Alan; Sharp, David J.; Gisslén, Magnus; Reiss, Peter; Winston, A.; Prins, M.; Schim van der Loeff, M. F.; Schouten, J.; Schmand, B.; Geurtsen, G. J.; Sharp, D. J.; Villaudy, J.; Berkhout, B.; Gisslén, M.; Pasternak, A.; Sabin, C. A.; Guaraldi, G.; Bürkle, A.; Libert, C.; Franceschi, C.; Kalsbeek, A.; Fliers, E.; Hoeijmakers, J.; Pothof, J.; van der Valk, M.; Bisschop, P. H.; Zaheri, S.; Burger, D.; Cole, J. H.; Zikkenheiner, W.; Janssen, F. R.; Underwood, J.; Kooij, K. W.; Doyle, N.; Verbraak, F.; Demirkaya, N.; Weijer, K.; Boeser-Nunnink, B.

    2018-01-01

    Background. Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods. We investigated factors associated with brain

  20. Evaluation of Brain and Cervical MRI Abnormality Rates in Patients With Systemic Lupus Erythematosus With or Without Neurological Manifestations

    International Nuclear Information System (INIS)

    Harirchian, Mohammad Hossein; Saberi, Hazhir; Najafizadeh, Seyed Reza; Hashemi, Seyed Ali

    2011-01-01

    Central nervous system (CNS) involvement has been observed in 14-80% of patients with systemic lupus erythematosus (SLE). Magnetic resonance imaging (MRI) is an appropriate method for evaluating CNS involvement in these patients. Clinical manifestations and MRI findings of CNS lupus should be differentiated from other mimicking diseases such as multiple sclerosis (MS). The aim of this study was to evaluate the prevalence and extent of brain and cervical cord MRI lesions of lupus patients. The relationship between neurological signs and symptoms and MRI findings were evaluated as well. Fifty SLE patients who had been referred to the rheumatology clinic of our hospital within 2009 were included in a cross sectional study. All patients fulfilled the revised 1981 American College of Rheumatology (ACR) criteria for SLE. We evaluated the neurological signs and symptoms and brain and cervical MRI findings in these patients. Forty-one patients (82%) were female and nine (18%) were male. The mean age was 30.1 ± 9.3 years. Twenty eight (56%) patients had an abnormal brain MRI. No one showed any abnormality in the cervical MRI. The lesions in 20 patients were similar to demyelinative plaques. Seventeen patients with abnormal brain MRI were neurologically asymptomatic. There was only a significant relationship between neurological motor manifestations and brain MRI abnormal findings. Unlike the brain, cervical MRI abnormality and especially asymptomatic cord involvement in MRI is quite rare in SLE patients. This finding may be helpful to differentiate SLE from other CNS disorders such as MS

  1. Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers.

    Science.gov (United States)

    van Zoest, Rosan A; Underwood, Jonathan; De Francesco, Davide; Sabin, Caroline A; Cole, James H; Wit, Ferdinand W; Caan, Matthan W A; Kootstra, Neeltje A; Fuchs, Dietmar; Zetterberg, Henrik; Majoie, Charles B L M; Portegies, Peter; Winston, Alan; Sharp, David J; Gisslén, Magnus; Reiss, Peter

    2017-12-27

    Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

    Science.gov (United States)

    Stevens, Michael C.; Haney-Caron, Emily

    2012-01-01

    Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is

  3. Aging and functional brain networks

    International Nuclear Information System (INIS)

    Tomasi D.; Volkow, N.D.

    2012-01-01

    Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

  4. Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Eun Yeon; Tae, Woo Suk; Kim, Sung Tae; Hong, Seung Bong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    To investigate gray matter concentration changes in the brains of narcoleptic patients. Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy

  5. Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

    International Nuclear Information System (INIS)

    Joo, Eun Yeon; Tae, Woo Suk; Kim, Sung Tae; Hong, Seung Bong

    2009-01-01

    To investigate gray matter concentration changes in the brains of narcoleptic patients. Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy

  6. Structural Brain Abnormalities in Juvenile Myoclonic Epilepsy Patients: Volumetry and Voxel-Based Morphometry

    International Nuclear Information System (INIS)

    Tae, Woo Suk; Hong, Seung Bong; Joo, Eun Yun

    2006-01-01

    We aimed to find structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients. The volumes of the cerebrum, hippocampus and frontal lobe and the area of the corpus callosum's subdivisions were all semiautomatically measured, and then optimized voxel-based morphometry (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls. The rostrum and rostral body of the corpus callosum and the left hippocampus were significantly smaller than those of the normal controls, whereas the volume of the JME's left frontal lobe was significantly larger than that of the controls. The area of the rostral body had a significant positive correlation with the age of seizure onset (r=0.56, p=0.012), and the volume of the right frontal lobe had a significant negative correlation with the duration of disease (r=-0.51, p=0.025). On the VBM, the gray matter concentration of the prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior middle frontal gyrus and right anterior superior frontal gyrus) was decreased in the JME group (corrected p<0.05). The JME patients showed complex structural abnormalities in the corpus callosum, frontal lobe and hippocampus, and also a decreased gray matter concentration of the prefrontal region, which all suggests there is an abnormal neural network in the JME brain

  7. Structural Brain Abnormalities in Juvenile Myoclonic Epilepsy Patients: Volumetry and Voxel-Based Morphometry

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk; Hong, Seung Bong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Joo, Eun Yun [Ewha Womans University, Seoul (Korea, Republic of)

    2006-09-15

    We aimed to find structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients. The volumes of the cerebrum, hippocampus and frontal lobe and the area of the corpus callosum's subdivisions were all semiautomatically measured, and then optimized voxel-based morphometry (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls. The rostrum and rostral body of the corpus callosum and the left hippocampus were significantly smaller than those of the normal controls, whereas the volume of the JME's left frontal lobe was significantly larger than that of the controls. The area of the rostral body had a significant positive correlation with the age of seizure onset (r=0.56, p=0.012), and the volume of the right frontal lobe had a significant negative correlation with the duration of disease (r=-0.51, p=0.025). On the VBM, the gray matter concentration of the prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior middle frontal gyrus and right anterior superior frontal gyrus) was decreased in the JME group (corrected p<0.05). The JME patients showed complex structural abnormalities in the corpus callosum, frontal lobe and hippocampus, and also a decreased gray matter concentration of the prefrontal region, which all suggests there is an abnormal neural network in the JME brain.

  8. Abnormal glutamate release in aged BTBR mouse model of autism

    OpenAIRE

    Wei, Hongen; Ding, Caiyun; Jin, Guorong; Yin, Haizhen; Liu, Jianrong; Hu, Fengyun

    2015-01-01

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses betw...

  9. Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers.

    Science.gov (United States)

    Cole, James H; Franke, Katja

    2017-12-01

    The brain changes as we age and these changes are associated with functional deterioration and neurodegenerative disease. It is vital that we better understand individual differences in the brain ageing process; hence, techniques for making individualised predictions of brain ageing have been developed. We present evidence supporting the use of neuroimaging-based 'brain age' as a biomarker of an individual's brain health. Increasingly, research is showing how brain disease or poor physical health negatively impacts brain age. Importantly, recent evidence shows that having an 'older'-appearing brain relates to advanced physiological and cognitive ageing and the risk of mortality. We discuss controversies surrounding brain age and highlight emerging trends such as the use of multimodality neuroimaging and the employment of 'deep learning' methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

    Science.gov (United States)

    Noordermeer, Siri D S; Luman, Marjolein; Greven, Corina U; Veroude, Kim; Faraone, Stephen V; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Heslenfeld, Dirk J; Oosterlaan, Jaap

    2017-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Kornreich, L; Horev, G; Schwarz, M; Karmazyn, B; Laron, Z

    2002-04-01

    To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

  12. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort.

    Science.gov (United States)

    Wade, Benjamin S C; Valcour, Victor G; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H; Gutman, Boris A; Thompson, Paul M

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%.

  13. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort

    Directory of Open Access Journals (Sweden)

    Benjamin S.C. Wade

    2015-01-01

    Full Text Available Over 50% of HIV+ individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD and radial distances (RD defined on each region's surfaces. We also investigated effects of nadir CD4+ T-cell counts, viral load, time since diagnosis (TSD and cognition on subcortical morphology. Lastly, we explored whether HIV+ participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF model. The model was validated with 2-fold cross-validation. Volumes of HIV+ participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV+ people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV+ participants vs. controls, our RF model attained an area under the curve of 72%.

  14. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    Science.gov (United States)

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM.

  15. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Qiu eXiangzhe

    2016-05-01

    Full Text Available Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM. However, the DM-related changes in the topological properties in functional brain networks are almost unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs, followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized shortest path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing the functional evidence for the abnormalities of brain networks in DM.

  16. Agrin in Alzheimer's Disease: Altered Solubility and Abnormal Distribution within Microvasculature and Brain Parenchyma

    Science.gov (United States)

    Donahue, John E.; Berzin, Tyler M.; Rafii, Michael S.; Glass, David J.; Yancopoulos, George D.; Fallon, Justin R.; Stopa, Edward G.

    1999-05-01

    Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with β -amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to β -amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

  17. Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

    Science.gov (United States)

    Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

    2018-02-01

    To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p 40). The volume of right middle frontal gyrus reduced significantly (p right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

  18. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  19. BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

    Science.gov (United States)

    Aas, Monica; Haukvik, Unn K; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia; Tesli, Martin S; Hellvin, Tone; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

    2013-10-01

    Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups. © 2013.

  20. Brain aging, Alzheimer's disease, and mitochondria

    Science.gov (United States)

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  1. Consequences on offspring of abnormal function in ageing gametes.

    Science.gov (United States)

    Tarín, J J; Pérez-Albalá, S; Cano, A

    2000-01-01

    The present review aims to analyse (i) the molecular, biochemical and cellular changes that accompany oocyte and sperm ageing in any of the internal or external environments where they can reside, and (ii) the consequences of the abnormal function in ageing gametes on pre- and post-implantation development and later life of offspring. This review also aims to propose and discuss cellular/molecular mechanisms framed within the 'free radical theory of ageing'. It appears that the ageing of gametes prior to fertilization may affect many molecular, biochemical and cellular pathways that may jeopardize not only pre- and post-implantation embryo/fetal development but also later life of offspring. Consequences of gamete ageing range from decreased vigour (with the concomitant decrease in intelligence, reproductive fitness and longevity) of apparently normal-looking offspring to severe congenital, epigenetic and/or genetic anomalies. All these effects may be easily prevented by efficient diffusion of both the potential risks of gamete ageing and the steps that should be taken by couples wishing to achieve pregnancy to guarantee a correct maturational synchronization of gametes at fertilization. Although in-vitro antioxidant therapy appears to protect from or retard the ageing process of gametes, it may not assure the total absence of negative effects on the resulting offspring.

  2. Brain perfusion abnormality in patients with chronic pain

    International Nuclear Information System (INIS)

    Honda, Tetsumi; Maruta, Toshihiko; Takahashi, Kumiko

    2007-01-01

    We performed single photon emission computed tomography (SPECT) of the brain in 15 patients with chronic pain (males, 7; females, 8; average age 49.1±17.9 years) and identified the locus of cerebral blood flow reduction by a new analytical method (easy Z-score Imaging System: eZIS) to clarify the functional neuroanatomical basis of chronic pain. Of the 15 patients, 6 had backache, 2 neck pain, 2 gonalgia, and 5 pain at other sites, with an average Visual analog scale of pain (VAS) value of 6.1±1.9. In comparison with a information on a data base on physically unimpaired persons, the dorsolateral prefrontal area (both sides, right dominant), medial prefrontal area (both sides), dorsal aspect of the anterior cingulate gyrus nociceptive cortex (both sides) and the lateral part of the orbitofrontal cortex (right side) were found to have blood flow reduction in the group of patients with chronic pain. As for chronic pain and its correlation with clinical features such as a depressive state, anticipation anxiety, post-traumatic stress disorder (PTSD), and conversion hysteria, the mechanism in the brain that was suggested by this study should be followed-up by functional neuroimaging studies. (author)

  3. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    Science.gov (United States)

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders.

  4. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

    Science.gov (United States)

    Altmann, Andre; Botía, Juan A; Jahanshad, Neda; Hibar, Derrek P; Absil, Julie; Alhusaini, Saud; Alvim, Marina K M; Auvinen, Pia; Bartolini, Emanuele; Bergo, Felipe P G; Bernardes, Tauana; Blackmon, Karen; Braga, Barbara; Caligiuri, Maria Eugenia; Calvo, Anna; Carr, Sarah J; Chen, Jian; Chen, Shuai; Cherubini, Andrea; David, Philippe; Domin, Martin; Foley, Sonya; França, Wendy; Haaker, Gerrit; Isaev, Dmitry; Keller, Simon S; Kotikalapudi, Raviteja; Kowalczyk, Magdalena A; Kuzniecky, Ruben; Langner, Soenke; Lenge, Matteo; Leyden, Kelly M; Liu, Min; Loi, Richard Q; Martin, Pascal; Mascalchi, Mario; Morita, Marcia E; Pariente, Jose C; Rodríguez-Cruces, Raul; Rummel, Christian; Saavalainen, Taavi; Semmelroch, Mira K; Severino, Mariasavina; Thomas, Rhys H; Tondelli, Manuela; Tortora, Domenico; Vaudano, Anna Elisabetta; Vivash, Lucy; von Podewils, Felix; Wagner, Jan; Weber, Bernd; Yao, Yi; Yasuda, Clarissa L; Zhang, Guohao; Bargalló, Nuria; Bender, Benjamin; Bernasconi, Neda; Bernasconi, Andrea; Bernhardt, Boris C; Blümcke, Ingmar; Carlson, Chad; Cavalleri, Gianpiero L; Cendes, Fernando; Concha, Luis; Delanty, Norman; Depondt, Chantal; Devinsky, Orrin; Doherty, Colin P; Focke, Niels K; Gambardella, Antonio; Guerrini, Renzo; Hamandi, Khalid; Jackson, Graeme D; Kälviäinen, Reetta; Kochunov, Peter; Kwan, Patrick; Labate, Angelo; McDonald, Carrie R; Meletti, Stefano; O'Brien, Terence J; Ourselin, Sebastien; Richardson, Mark P; Striano, Pasquale; Thesen, Thomas; Wiest, Roland; Zhang, Junsong; Vezzani, Annamaria; Ryten, Mina; Thompson, Paul M

    2018-01-01

    Abstract Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen’s d = −0.24 to −0.73; P left, but not right, MTLE (d = −0.29 to −0.54; P right, but not left, MTLE (d = −0.27 to −0.51; P right MTLE groups (beta, b brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed. PMID:29365066

  5. Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study.

    Science.gov (United States)

    Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

    2016-06-01

    Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question. In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia ("schizophrenia score"), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age ("brain age gap") and between schizophrenia score and healthy reference score ("schizophrenia gap") were calculated. Accelerated brain aging was calculated from changes in brain age gap between two consecutive measurements. The age prediction model was validated in an independent sample. In schizophrenia patients, brain age was significantly greater than chronological age at baseline (+3.36 years) and progressively increased during follow-up (+1.24 years in addition to the baseline gap). The acceleration of brain aging was not constant: it decreased from 2.5 years/year just after illness onset to about the normal rate (1 year/year) approximately 5 years after illness onset. The schizophrenia gap also increased during follow-up, but more pronounced variability in brain abnormalities at follow-up rendered this increase nonsignificant. The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and

  6. Brain abnormalities detected on magnetic resonance imaging of amphetamine users presenting to an emergency department: a pilot study.

    Science.gov (United States)

    Fatovich, Daniel M; McCoubrie, David L; Song, Swithin J; Rosen, David M; Lawn, Nick D; Daly, Frank F

    2010-09-06

    To determine the prevalence of occult brain abnormalities in magnetic resonance imaging of active amphetamine users. Prospective convenience study in a tertiary hospital emergency department (ED). Patients presenting to the ED for an amphetamine-related reason were eligible for inclusion. We collected demographic data, drug use data, and performed a mini-mental state examination (MMSE). The proportion of patients with an abnormality on their MRI scan. Of 38 patients enrolled, 30 had MRI scans. Nineteen were male and their mean age was 26.7 +/- 5.4 years (range 19-41 years). The mean age of first amphetamine use was 18 years (range 13-26 years). Sixteen patients used crystal methamphetamine (mean amount 2.5 g/week), nine used amphetamine ("speed") (mean amount 2.9 g/week), and 23 used ecstasy (mean amount 2.3 tablets/week). Marijuana was smoked by 26 (mean amount 5.9 g/week), and 28 drank alcohol (mean amount 207 g/week). The median MMSE score was 27/30 (interquartile range, 26-29). Abnormalities on brain MRI scans were identified in six patients, most commonly an unidentified bright object (n = 4). In this pilot study of brain MRI of young people attending the ED with an amphetamine-related presentation, one in five had an occult brain lesion. While the significance of this is uncertain, it is congruent with evidence that amphetamines cause brain injury.

  7. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease.

    Directory of Open Access Journals (Sweden)

    Zhigang Bai

    Full Text Available To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD and examine the relationship between brain microstructure and physiological indictors in the disease.Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18-61 years and 40 age- and gender-matched healthy controls (HCs, 32 men, 22-58 years. A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients.Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM but also gray matter (GM regions, as characterized by decreased fractional anisotropy (FA and increased mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD. Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part in the patients.Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease.

  8. Neurobehavioral Abnormalities Associated with Executive Dysfunction after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Rodger Ll. Wood

    2017-10-01

    Full Text Available Objective: This article will address how anomalies of executive function after traumatic brain injury (TBI can translate into altered social behavior that has an impact on a person’s capacity to live safely and independently in the community.Method: Review of literature on executive and neurobehavioral function linked to cognitive ageing in neurologically healthy populations and late neurocognitive effects of serious TBI. Information was collated from internet searches involving MEDLINE, PubMed, PyscINFO and Google Scholar as well as the authors’ own catalogs.Conclusions: The conventional distinction between cognitive and emotional-behavioral sequelae of TBI is shown to be superficial in the light of increasing evidence that executive skills are critical for integrating and appraising environmental events in terms of cognitive, emotional and social significance. This is undertaken through multiple fronto-subcortical pathways within which it is possible to identify a predominantly dorsolateral network that subserves executive control of attention and cognition (so-called cold executive processes and orbito-frontal/ventro-medial pathways that underpin the hot executive skills that drive much of behavior in daily life. TBI frequently involves disruption to both sets of executive functions but research is increasingly demonstrating the role of hot executive deficits underpinning a wide range of neurobehavioral disorders that compromise relationships, functional independence and mental capacity in daily life.

  9. Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

    Science.gov (United States)

    Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

    2017-03-01

    The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients.

    Science.gov (United States)

    Bubber, P; Hartounian, V; Gibson, G E; Blass, J P

    2011-03-01

    Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured the activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, pTCA cycle, were lower, but SDH (18.3%, pTCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r=0.55, p=003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  11. Surgical management of abnormal uterine bleeding in fertile age women.

    Science.gov (United States)

    Finco, Andrea; Centini, Gabriele; Lazzeri, Lucia; Zupi, Errico

    2015-07-01

    Abnormal uterine bleeding is a common gynecological disease and represents one of the most frequent reasons for hospital admission to a specialist unit, often requiring further surgical treatment. Following the so-called PALM-COEIN system we will attempt to further clarify the surgical treatments available today. The first group (PALM) is characterized by structural lesions, which may be more appropriately treated by means of surgical management. Although hysterectomy remains the definitive and decisive choice, there are many alternative techniques available. These minimally invasive procedures offer the opportunity for a more conservative approach. Precise and accurate counseling facilitates better patient selection, based on the patient's desires, age and disease type, allowing treatment to be individually tailored to each woman.

  12. Abnormal resting-state brain activities in patients with first-episode obsessive-compulsive disorder.

    Science.gov (United States)

    Niu, Qihui; Yang, Lei; Song, Xueqin; Chu, Congying; Liu, Hao; Zhang, Lifang; Li, Yan; Zhang, Xiang; Cheng, Jingliang; Li, Youhui

    2017-01-01

    This paper attempts to explore the brain activity of patients with obsessive-compulsive disorder (OCD) and its correlation with the disease at resting duration in patients with first-episode OCD, providing a forceful imaging basis for clinic diagnosis and pathogenesis of OCD. Twenty-six patients with first-episode OCD and 25 healthy controls (HC group; matched for age, sex, and education level) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Statistical parametric mapping 8, data processing assistant for resting-state fMRI analysis toolkit, and resting state fMRI data analysis toolkit packages were used to process the fMRI data on Matlab 2012a platform, and the difference of regional homogeneity (ReHo) values between the OCD group and HC group was detected with independent two-sample t -test. With age as a concomitant variable, the Pearson correlation analysis was adopted to study the correlation between the disease duration and ReHo value of whole brain. Compared with HC group, the ReHo values in OCD group were decreased in brain regions, including left thalamus, right thalamus, right paracentral lobule, right postcentral gyrus, and the ReHo value was increased in the left angular gyrus region. There was a negative correlation between disease duration and ReHo value in the bilateral orbitofrontal cortex (OFC). OCD is a multifactorial disease generally caused by abnormal activities of many brain regions at resting state. Worse brain activity of the OFC is related to the OCD duration, which provides a new insight to the pathogenesis of OCD.

  13. Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

    Science.gov (United States)

    Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

    2017-07-01

    Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

  14. Brain perfusion studies in the evaluation of acute neurologic abnormalities.

    Science.gov (United States)

    Zuckier, Lionel S; Sogbein, O O

    2013-03-01

    Two categories of single-photon radiopharmaceuticals for brain perfusion exist, nonlipophilic and lipophilic compounds. The former are useful in performing simple flow examinations which today have application primarily in the determination of brain death. The latter also exhibit a parenchymal uptake phase that allows for evaluation of the distribution of blood flow within the brain. The lipophilic radiopharmaceuticals, therefore, have application in the evaluation of patients following catastrophic brain injury and traumatic brain injury (TBI) and in prognosticating the outcome following cerebral vascular accidents. Use of these agents to monitor therapy with thrombolytic agents, although theoretically helpful, is technically difficult due to the need to institute treatment rapidly, without undue delay. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Brain MRI signal abnormalities and right-to-left shunting in asymptomatic military divers.

    Science.gov (United States)

    Gempp, Emmanuel; Sbardella, Fabrice; Stephant, Eric; Constantin, Pascal; De Maistre, Sebastien; Louge, Pierre; Blatteau, Jean-Eric

    2010-11-01

    We conducted a controlled study to assess the prevalence of brain MRI hyperintense signals and their correlation with right-to-left shunting (RLS) in military divers. We prospectively enrolled 32 asymptomatic military divers under 41 yr of age and 32 non-diving healthy subjects matched with respect to age and vascular disease risk factors. We examined both groups with a 3-Tesla brain MRI; RLS was detected using transcranial pulsed Doppler in divers only. Hyperintense spots were observed in 43.7% of the divers and 21.8% of the control subjects. In particular, divers with significant shunting exhibited a higher prevalence of hyperintensities compared to those with slight or no RLS (75% vs. 25%, respectively). Linear trend analysis also revealed a positive correlation between focal white matter changes, determined using a validated visual rating scale and the RLS grade. Healthy military divers with a hemodynamically relevant RLS have an increased likelihood of cerebral hyperintense spots compared to age-matched normal subjects. The clinical relevance of these MRI signal abnormalities and their causal relationship with diving remain unclear.

  16. Effects of smoking on brain aging, 1

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Matsuzawa, Taiju; Yamaguchi, Tatsuo; Fujiwara, Takehiko; Seo, Shinya; Sasaki, Yuichiro.

    1985-01-01

    The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects from 25 to 85 years old were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. A hundred and twentyfive subjects who had no abnormalities in neurological examinations nor in CT scan, were divided into two groups smokers (48) and non-smokers (77). Those who had a smoking index (Number of cigarettes/day) x (years of smoking history)>200 were designated as smokers. The mean smoking index of smokers was 697. sixty-five of the 77 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 16. Increased reduction of CBF with advancing age was clearly observed. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF 15% lower in smokers, p<0.001). Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduced CBF. Age dependent decrease of CBF was deteriorated by chronic smoking. Then, chronic smoking was suggested to be a risk factor for brain aging. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels. (author)

  17. Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

    Science.gov (United States)

    Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

    2016-12-01

    Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

  18. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    Science.gov (United States)

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  19. Brain perfusion abnormalities associated to drug abuse in recent abstinent patients using SPECT 99m Tc-ethylen-cysteinate-dimer (ECD)

    Energy Technology Data Exchange (ETDEWEB)

    Massardo, Teresa [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile); Pallavicini, Julio [Addiction Unit, Psychiatric Clinic. University of Chile Clinical Hospital (Chile); Gonzalez, Patricio; Jaimovich, Rodrigo [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile); Servat, Monica [Addiction Unit, Psychiatric Clinic. University of Chile Clinical Hospital (Chile); Lavados, Hugo [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile); Arancibia, Pablo [Addiction Unit, Psychiatric Clinic. University of Chile Clinical Hospital (Chile); Padilla, Pamela [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile)

    2009-04-15

    Several substances may produce brain perfusion abnormalities in drug-dependent patients. Their mechanism is unclear and several causes might be involved, especially vasospasm in cocaine consumption. Goal: To characterize residual brain perfusion abnormalities in substance-dependent population. We analyzed brain perfusion in 100 dependant patients (DSM-IV criteria) following a month of strict in-hospital abstinence (age:35{+-}12 y.o.; 86% men); 55% corresponded to poly-drug dependents, mainly to cocaine, alcohol and cannabis; 44% mono-drug users, mostly to alcohol. Results: Single Photon Emission Computed Tomography (SPECT) with 99mTc-ethylen-cysteinate-dimer (ECD) was abnormal in 54% of the cases, with bilateral cortical hypo-perfusion in 89%, focal in 54% and diffuse in 46% of them, with moderate or severe intensity in 61%. The abnormal perfusion group's age was 38{+-}12 versus 31{+-}10 years in the normal SPECT group (P=0.005) with a consumption period of 16{+-}11 versus 11{+-}8 years, respectively (P=0.043). Only 29% of women had abnormal perfusion versus 58% of men (P=0.047). Abnormal brain perfusion in 64% of mono and 45% in poly-drug dependents (P=0.07). Psychometric tests performed in 25 patients demonstrated association between perfusion defects and cognitive abnormalities. Relative risk for abnormal psychometric test was 2.5 [95%;CI=1.1-5.6] for abnormal SPECT. Conclusion: Dependent population after a month of abstinence persists with cortical brain perfusion abnormalities, associated to age, sex and type of drug consumption.

  20. Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

    Science.gov (United States)

    Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

    2011-01-01

    The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

  1. The aging brain and neurodegenerative disorders

    International Nuclear Information System (INIS)

    Braffman, B.H.; Trojanowski, J.Q.; Atlas, S.W.

    1991-01-01

    Both the aging brain and neurodegenerative disorders are characterized by a lack of vital endurance of affected neurons resulting in their premature death. Neuronal shrinkage or atrophy and death are normal and inevitable aspects of normal or successful aging; this is unexpected, excessive, and premature in neurodegenerative disorders. These histologic changes result in the neuroimaging findings of focal and/or diffuse atrophy with consequent enlargement of cerebrospinal fluid (CSF) spaces. The aging brain and neurodegenerative disorders share other magnetic resonance (MR) changes, i.e., markedly hypointense extrapyramidal nuclei and hyperintense white matter foci. The sequelae of senescent vascular changes result in additional characteristic features of the aging brain. This paper presents the MR and neuropathologic manifestations of both the normal aging brain and the brain affected by neurodegenerative disorders

  2. Developmental vitamin D deficiency causes abnormal brain development.

    Science.gov (United States)

    Eyles, D W; Feron, F; Cui, X; Kesby, J P; Harms, L H; Ko, P; McGrath, J J; Burne, T H J

    2009-12-01

    There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that

  3. Abnormal brain activation in excoriation (skin-picking) disorder

    DEFF Research Database (Denmark)

    Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R

    2016-01-01

    Background: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims: To probe the function of fronto-striatal circuitry in SPD. Method: Eighteen participants with SPD and 15 matched healthy controls undertook an executive...... encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions: Abnormalities of neural regions...... involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders....

  4. NIH Conference. Brain imaging: aging and dementia

    International Nuclear Information System (INIS)

    Cutler, N.R.; Duara, R.; Creasey, H.; Grady, C.L.; Haxby, J.V.; Schapiro, M.B.; Rapoport, S.I.

    1984-01-01

    The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

  5. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS

    Directory of Open Access Journals (Sweden)

    Johnston Jennifer

    2011-07-01

    Full Text Available Abstract Background Bardet-Biedl syndrome (BBS is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1 normal intracranial volume; 2 reduced white matter in all regions of the brain, but most in the occipital region; 3 preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4 reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5 increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes

  6. Brain age and other bodily 'ages': implications for neuropsychiatry.

    Science.gov (United States)

    Cole, James H; Marioni, Riccardo E; Harris, Sarah E; Deary, Ian J

    2018-06-11

    As our brains age, we tend to experience cognitive decline and are at greater risk of neurodegenerative disease and dementia. Symptoms of chronic neuropsychiatric diseases are also exacerbated during ageing. However, the ageing process does not affect people uniformly; nor, in fact, does the ageing process appear to be uniform even within an individual. Here, we outline recent neuroimaging research into brain ageing and the use of other bodily ageing biomarkers, including telomere length, the epigenetic clock, and grip strength. Some of these techniques, using statistical approaches, have the ability to predict chronological age in healthy people. Moreover, they are now being applied to neurological and psychiatric disease groups to provide insights into how these diseases interact with the ageing process and to deliver individualised predictions about future brain and body health. We discuss the importance of integrating different types of biological measurements, from both the brain and the rest of the body, to build more comprehensive models of the biological ageing process. Finally, we propose seven steps for the field of brain-ageing research to take in coming years. This will help us reach the long-term goal of developing clinically applicable statistical models of biological processes to measure, track and predict brain and body health in ageing and disease.

  7. Normal and abnormal neuronal migration during brain development

    International Nuclear Information System (INIS)

    Rakic, P.

    1986-01-01

    Conceptual and factual advances in understanding neuronal migration in the past two decades have provided new insight into the pathogenesis of brain malformations at the cellular, molecular, and functional levels. Some of these results may have direct implications in understanding the consequences of ionizing radiation on the fetal central nervous system in utero. (orig.)

  8. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  9. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

    Directory of Open Access Journals (Sweden)

    Wen Miao

    Full Text Available To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1 patients using multimodal MRI imaging.T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls.Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (p<0.001 uncorrected in the left precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus.CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

  10. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

    Science.gov (United States)

    Miao, Wen; Man, Fengyuan; Wu, Shaoqin; Lv, Bin; Wang, Zhenchang; Xian, Junfang; Sabel, Bernhard A; He, Huiguang; Jiao, Yonghong

    2015-01-01

    To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (pleft precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus. CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

  11. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study

    Science.gov (United States)

    Wu, Shaoqin; Lv, Bin; Wang, Zhenchang; Xian, Junfang; Sabel, Bernhard A.; He, Huiguang; Jiao, Yonghong

    2015-01-01

    Purpose To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. Methods T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender- matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Results Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (pleft precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus. Conclusions CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1. PMID:26186732

  12. Genome instability: Linking ageing and brain degeneration.

    Science.gov (United States)

    Barzilai, Ari; Schumacher, Björn; Shiloh, Yosef

    2017-01-01

    Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-associated decline of brain functionality and the detrimental effect of genome instability on brain functionality and development. This review discusses these similarities and differences and highlights cell classes whose role in these processes might have been underestimated-glia and microglia. Copyright © 2016. Published by Elsevier B.V.

  13. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, William Frans Christian; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder...... that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis....

  14. Abnormal uterine bleeding in reproductive-aged women.

    Science.gov (United States)

    Matthews, Michelle L

    2015-03-01

    Abnormal uterine bleeding is a common medical condition with several causes. The International Federation of Gynecology and Obstetrics published guidelines in 2011 to develop universally accepted nomenclature and a classification system. In addition, the American College of Obstetrics and Gynecology recently updated recommendations on evaluation of abnormal uterine bleeding and indications for endometrial biopsies. This article reviews both medical and surgical treatments, including meta-analysis reviews of the most effective treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    International Nuclear Information System (INIS)

    Cianfoni, A.; Caulo, M.; Cerase, A.; Della Marca, G.; Falcone, C.; Di Lella, G.M.; Gaudino, S.; Edwards, J.; Colosimo, C.

    2013-01-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention

  16. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

    2013-11-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

  17. Harvard Aging Brain Study : Dataset and accessibility

    NARCIS (Netherlands)

    Dagley, Alexander; LaPoint, Molly; Huijbers, Willem; Hedden, Trey; McLaren, Donald G.; Chatwal, Jasmeer P.; Papp, Kathryn V.; Amariglio, Rebecca E.; Blacker, Deborah; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Schultz, Aaron P.

    2017-01-01

    The Harvard Aging Brain Study is sharing its data with the global research community. The longitudinal dataset consists of a 284-subject cohort with the following modalities acquired: demographics, clinical assessment, comprehensive neuropsychological testing, clinical biomarkers, and neuroimaging.

  18. Abnormal brain structure in youth who commit homicide

    Science.gov (United States)

    Cope, L.M.; Ermer, E.; Gaudet, L.M.; Steele, V.R.; Eckhardt, A.L.; Arbabshirani, M.R.; Caldwell, M.F.; Calhoun, V.D.; Kiehl, K.A.

    2014-01-01

    Background Violence that leads to homicide results in an extreme financial and emotional burden on society. Juveniles who commit homicide are often tried in adult court and typically spend the majority of their lives in prison. Despite the enormous costs associated with homicidal behavior, there have been no serious neuroscientific studies examining youth who commit homicide. Methods Here we use neuroimaging and voxel-based morphometry to examine brain gray matter in incarcerated male adolescents who committed homicide (n = 20) compared with incarcerated offenders who did not commit homicide (n = 135). Two additional control groups were used to understand further the nature of gray matter differences: incarcerated offenders who did not commit homicide matched on important demographic and psychometric variables (n = 20) and healthy participants from the community (n = 21). Results Compared with incarcerated adolescents who did not commit homicide (n = 135), incarcerated homicide offenders had reduced gray matter volumes in the medial and lateral temporal lobes, including the hippocampus and posterior insula. Feature selection and support vector machine learning classified offenders into the homicide and non-homicide groups with 81% overall accuracy. Conclusions Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses. PMID:24936430

  19. Structural imaging measures of brain aging.

    Science.gov (United States)

    Lockhart, Samuel N; DeCarli, Charles

    2014-09-01

    During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

  20. Normal and abnormal fetal brain development during the third trimester as demonstrated by neurosonography

    International Nuclear Information System (INIS)

    Malinger, G.; Lev, D.; Lerman-Sagie, T.

    2006-01-01

    The multiplanar neurosonographic examination of the fetus enables superb visualization of brain anatomy during pregnancy. The examination may be performed using a transvaginal or a transfundal approach and it is indicated in patients at high risk for CNS anomalies or in those with a suspicious finding during a routine examination. The purpose of this paper is to present a description of the normal brain and of abnormal findings usually diagnosed late in pregnancy, including malformations of cortical development, infratentorial anomalies, and prenatal insults

  1. Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.

    Science.gov (United States)

    Guo, Hao; Cao, Xiaohua; Liu, Zhifen; Li, Haifang; Chen, Junjie; Zhang, Kerang

    2012-12-05

    Resting state functional brain networks have been widely studied in brain disease research. However, it is currently unclear whether abnormal resting state functional brain network metrics can be used with machine learning for the classification of brain diseases. Resting state functional brain networks were constructed for 28 healthy controls and 38 major depressive disorder patients by thresholding partial correlation matrices of 90 regions. Three nodal metrics were calculated using graph theory-based approaches. Nonparametric permutation tests were then used for group comparisons of topological metrics, which were used as classified features in six different algorithms. We used statistical significance as the threshold for selecting features and measured the accuracies of six classifiers with different number of features. A sensitivity analysis method was used to evaluate the importance of different features. The result indicated that some of the regions exhibited significantly abnormal nodal centralities, including the limbic system, basal ganglia, medial temporal, and prefrontal regions. Support vector machine with radial basis kernel function algorithm and neural network algorithm exhibited the highest average accuracy (79.27 and 78.22%, respectively) with 28 features (Pdisorder is associated with abnormal functional brain network topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms.

  2. Chromosomal abnormalities are associated with aging and cancer

    Science.gov (United States)

    Two new studies have found that large structural abnormalities in chromosomes, some of which have been associated with increased risk of cancer, can be detected in a small fraction of people without a prior history of cancer. The studies found that these

  3. BrainAGE score indicates accelerated brain aging in schizophrenia, but not bipolar disorder.

    Science.gov (United States)

    Nenadić, Igor; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

    2017-08-30

    BrainAGE (brain age gap estimation) is a novel morphometric parameter providing a univariate score derived from multivariate voxel-wise analyses. It uses a machine learning approach and can be used to analyse deviation from physiological developmental or aging-related trajectories. Using structural MRI data and BrainAGE quantification of acceleration or deceleration of in individual aging, we analysed data from 45 schizophrenia patients, 22 bipolar I disorder patients (mostly with previous psychotic symptoms / episodes), and 70 healthy controls. We found significantly higher BrainAGE scores in schizophrenia, but not bipolar disorder patients. Our findings indicate significantly accelerated brain structural aging in schizophrenia. This suggests, that despite the conceptualisation of schizophrenia as a neurodevelopmental disorder, there might be an additional progressive pathogenic component. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  4. IGF-1: The Jekyll & Hyde of the aging brain.

    Science.gov (United States)

    Gubbi, Sriram; Quipildor, Gabriela Farias; Barzilai, Nir; Huffman, Derek M; Milman, Sofiya

    2018-05-08

    The IGF-1 signaling pathway has emerged as a major regulator of the aging process, from rodents to humans. However, given the pleiotropic actions of IGF-1, its role in the aging brain remains complex and controversial. While IGF-1 is clearly essential for normal development of the central nervous system, conflicting evidence has emerged from preclinical and human studies regarding its relationship to cognitive function, as well as cerebrovascular and neurodegenerative disorders. This review delves into the current state of the evidence examining the role of IGF-1 in the aging brain, encompassing preclinical and clinical studies. A broad examination of the data indicates that IGF-1 may indeed play opposing roles in the aging brain, depending on the underlying pathology and context. Some evidence suggests that in the setting of neurodegenerative diseases that manifest with abnormal protein deposition in the brain, such as Alzheimer's disease, reducing IGF-1 signaling may serve a protective role by slowing disease progression and augmenting clearance of pathologic proteins to maintain cellular homeostasis. In contrast, inducing IGF-1 deficiency has also been implicated in dysregulated function of cognition and the neurovascular system, suggesting that some IGF-1 signaling may be necessary for normal brain function. Furthermore, states of acute neuronal injury, which necessitate growth, repair and survival signals to persevere, typically demonstrate salutary effects of IGF-1 in that context. Appreciating the dual, at times opposing "Dr. Jekyll" and "Mr. Hyde" characteristics of IGF-1 in the aging brain, will bring us closer to understanding its impact and devising more targeted IGF-1-related interventions.

  5. Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

    Directory of Open Access Journals (Sweden)

    Janušonis Skirmantas

    2005-07-01

    Full Text Available Abstract Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin in blood platelets (platelet hyperserotonemia. The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene based on currently available clinical and

  6. Abnormalities in Human Brain Creatine Metabolism in Gulf War Illness Probed with MRS

    Science.gov (United States)

    2014-12-01

    TYPE Final 3. DATES COVERED 30 Sep 2012 - 29 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Abnormalities in Human Brain Creatine Metabolism in...levels of total creatine (tCr) in veterans with Gulf War Illness have been observed in prior studies. The goal of this research is to estimate amounts and

  7. Age distribution of abnormal pap smear in a secondary hospital in ...

    African Journals Online (AJOL)

    Age distribution of abnormal pap smear in a secondary hospital in south-west Nigeria. ... Objective: To determine the age distribution pattern of abnormal Paps smear in women in our environment in order to have a basis for the points of entry and exit for cervical cancer screening protocol. Materials and Method: In this ...

  8. Congenital brain abnormalities: an update on malformations of cortical development and infratentorial malformations.

    Science.gov (United States)

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2014-07-01

    In the past two decades, significant progress in neuroimaging and genetic techniques has allowed for advances in the correct definition/classification of congenital brain abnormalities, which have resulted in a better understanding of their pathogenesis. In addition, new groups of diseases, such as axonal guidance disorders or tubulinopathies, are increasingly reported. Well-defined neuroimaging diagnostic criteria have been suggested for the majority of congenital brain abnormalities. Accurate diagnoses of these complex abnormalities, including distinction between malformations and disruptions, are of paramount significance for management, prognosis, and family counseling. In the next decade, these advances will hopefully be translated into deeper understanding of these disorders and more specific treatments. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  10. Changes in brain CT with aging

    International Nuclear Information System (INIS)

    Hiraiwa, Mikio; Abe, Toshiaki; Nonaka, Chizuru

    1983-01-01

    We have devised a new method for the objective evaluation of brain CT, a two-dimensional measurement: Two-dimensional measurement is based not on the developed films, but on treating raw data from magnetic tape. On the basis of our application of this method, we have discussed the changes in brain CT with aging. 135 patients, 72 males and 63 females, aged from 10 days to 78 years old, were subjected. The intracranial area showed a significant increase under 2 years old, but no marked changes after 3 years of age. The brain area increased under 2 years of age, and decreased after one's forties. The ventricular area showed no significant changes until the forties, but gradually increased thereafter. The bifrontal fluid-collection area was prominent in infancy, was almost invisible between 3 and 50 years of age and thereafter grew larger. For a relative comparison of brain CT scans with different intracranial areas, we devised three indices; BAI (brain-area index; brain area x 100/intracranial area), VAI (ventricular-area index; ventricular area x 100/intracranial area), and BFCI (bifrontal fluid-collection-area index; bifrontal fluid-collection area x 100/intracranial area). The BAI was low in infancy (under 95), was 96-97 between 3 and 50 years of age, and slowly decreased thereafter (88 in seventies). The VAI was under 2 until 50 years of age and gradually increased thereafter. The BFCI was high (over 3) in infancy and 0.2-0.4 between 3 and 50 years of age, and slowly increased thereafter. (J.P.N.)

  11. Nutrition, brain aging, and neurodegeneration

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases superimposed on a declining nervous system could enhance the motor and cognitive behavioral deficits that normally occur in senescence. It is likely that, in cases of severe deficits in memory or motor function, hospitalization and/or custodial car...

  12. Diffusion tensor MR imaging in neurofibromatosis type 1: expanding the knowledge of microstructural brain abnormalities

    International Nuclear Information System (INIS)

    Ferraz-Filho, Jose R.L.; Muniz, Marcos P.; Souza, Antonio S.; Rocha, Antonio J. da; Goloni-Bertollo, Eny M.; Pavarino-Bertelli, Erika C.

    2012-01-01

    Neurofibromatosis type 1 (NF1) is a hereditary disease with a dominant autosomal pattern. In children and adolescents, it is frequently associated with the appearance of T2-weighted hyperintensities in the brain's white matter. MRI with diffusion tensor imaging (DTI) is used to detect white matter abnormalities by measuring fractional anisotropy (FA). This study employed DTI to evaluate the relationship between FA patterns and the findings of T2 sequences, with the aim of improving our understanding of anatomical changes and microstructural brain abnormalities in individuals with NF1. Forty-four individuals with NF1 and 20 control subjects were evaluated. The comparative analysis of FA between NF1 and control groups was based on four predetermined anatomical regions of the brain hemispheres (basal ganglia, cerebellum, pons, thalamus) and related the presence or absence of T2-weighted hyperintensities in the brain, which are called unidentified bright objects (UBOs). The FA values between the groups demonstrated statistically significant differences (P ≤ 0.05) for the cerebellum and thalamus in patients with NF1, independent of the occurrence of UBOs. Diffusion tensor MR imaging confirms the influence of UBOs in the decrease of FA values in this series of patients with NF1. Additionally, this technique allows the characterization of microstructural abnormalities even in some brain regions that appear normal in conventional MR sequences. (orig.)

  13. Metabolic drift in the aging brain.

    Science.gov (United States)

    Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

  14. Large-Scale Functional Brain Network Abnormalities in Alzheimer’s Disease: Insights from Functional Neuroimaging

    Directory of Open Access Journals (Sweden)

    Bradford C. Dickerson

    2009-01-01

    Full Text Available Functional MRI (fMRI studies of mild cognitive impairment (MCI and Alzheimer’s disease (AD have begun to reveal abnormalities in large-scale memory and cognitive brain networks. Since the medial temporal lobe (MTL memory system is a site of very early pathology in AD, a number of studies have focused on this region of the brain. Yet it is clear that other regions of the large-scale episodic memory network are affected early in the disease as well, and fMRI has begun to illuminate functional abnormalities in frontal, temporal, and parietal cortices as well in MCI and AD. Besides predictable hypoactivation of brain regions as they accrue pathology and undergo atrophy, there are also areas of hyperactivation in brain memory and cognitive circuits, possibly representing attempted compensatory activity. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. Additional work with “resting state” fMRI data is illuminating functional-anatomic brain circuits and their disruption by disease. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, which will hopefully one day be useful for demonstrating beneficial effects of treatments being tested in clinical trials.

  15. Advanced BrainAGE in older adults with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2013-12-01

    Full Text Available Aging alters brain structure and function and diabetes mellitus (DM may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain MRIs. The Brain Age Gap Estimation (i.e., BrainAGE score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM completed an MRI at 3T, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001, whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034, whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor (TNFα levels, lower verbal fluency scores and more severe depression. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019 and increased fasting blood glucose levels (r = 0.34, p = 0.025. In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM.

  16. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  17. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    International Nuclear Information System (INIS)

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W.

    1997-01-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84±17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78±10.36), mild defect ( 2 test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients

  18. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84{+-}17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78{+-}10.36), mild defect (<50MQ : n=9, MQ=66.11{+-}13.87). The degree of rCBF decrease between the two groups was evaluated by {chi}{sup 2} test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients.

  19. Abnormal serotonin transporter availability in the brains of adults with conduct disorder.

    Science.gov (United States)

    Chang, Chieh; Gau, Susan Shur-Fen; Huang, Wen-Sheng; Shiue, Chyng-Yann; Yeh, Chin-Bin

    2017-06-01

    The aims of the current study were to determine whether patients with conduct disorder (CD) showed an abnormal availability of serotonin reuptake transporter (SERT), and if their hyperkinetic symptoms, impulsivity, and quality of life were correlated with the availability of SERT. We recruited 14 drug-naïve patients with CD and eight age-matched healthy controls (HCs). The adult attention-deficit/hyperactivity disorder (ADHD) self-report scale (ASRS), Barrett impulsivity scale (BIS), and the World Health Organization quality of life-brief version (WHOQOL-BREF) scale were administered. Positron emission tomography (PET) of the brain with 4-[ 18 F]-ADAM was arranged for SERT imaging. SERT availability was significantly reduced in the striatum and midbrain of patients with CD. Quality of life and inattention symptoms were also significantly correlated with the availability of SERT in the prefrontal cortex. The study suggested that a reduction in the availability of SERT might be associated with CD and could potentially predict poor quality of life or symptoms of inattention for these patients. The implications of our results might be limited to individuals with CD; a future study with a larger sample to validate our preliminary results is warranted. Copyright © 2016. Published by Elsevier B.V.

  20. Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

    Science.gov (United States)

    Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

    1985-10-01

    We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

  1. Abnormal brain MRI in a case of acute ataxia as the only sign of abdominal neuroblastoma

    International Nuclear Information System (INIS)

    Molla Mohammadi, M.; Karimzadeh, P.; Khatami, A.; Jadali, F.

    2010-01-01

    Ataxia is a movement disorder that may manifest an acute, intermittent, non progressive or chronic progressive course. Ataxia alone is rare as a para neoplastic sign, especially if it is due to neuroblastoma (abdominal or chest). We report an abdominal neuroblastoma in a two-year-old girl presenting with only acute ataxia and abnormal neuroimaging. Brain MRI showed abnormal signal finding in the medulla, pons, cortico spinal tract and the periventricular space. In the abdominal CT, a mass was detected in the right adrenal gland with calcification and the histopathologic examination re-vealed neuroblastoma. We suggest in children with acute ataxia, with or without opalescence-myoclonus, neuroblastoma should be considered.

  2. Brain computed tomography findings of aged schizophrenics

    International Nuclear Information System (INIS)

    Oomori, Masao; Koshino, Yoshifumi; Murata, Tetsuhito; Murata, Ichirou; Tani, Kazuhiko; Horie, Tan; Isaki, Kiminori

    1992-01-01

    Brain CT was performed in a total of 30 aged schizophrenic patients, consisting of 20 with no history of psychosurgery (lobotomy) and the other 10 lobotomized patients. The CT findings were compared with those from healthy aged persons. The group of schizophrenic patients had marked atrophy of the frontal lobe and dilatated Sylvian fissure as compared with the control group. There was no significant difference in ventricular factors between the two groups. These findings may have implications for the different mechanisms of the occurrence of atrophied brain surface and enlarged ventricle. The cerebral cortex involved in the occurrence of schizophrenia may be affected by aging-related cerebral atrophy, in addition to the morphological changes due to schizophrenia. Thus, schizophrenic cerebral atrophy was more noticeable than physiological aging-related atrophy. However, enlargement of the ventricle in the schizophrenic group progressed with aging in the same manner as that in the normal group. In comparing schizophrenic patients with or without a history of lobotomy, atrophy of the brain surface and enlargement of the ventricle were more marked in the lobotomized patients than the non-lobotomized patients. This confirmed that lobotomy, as well as surgical scar, is involved in the morphology of schizophrenic brain. (N.K.)

  3. The Impact of Traumatic Brain Injury on the Aging Brain.

    Science.gov (United States)

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident.

  4. Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.

    Science.gov (United States)

    Muellner, Julia; Delmaire, Christine; Valabrégue, Romain; Schüpbach, Michael; Mangin, Jean-François; Vidailhet, Marie; Lehéricy, Stéphane; Hartmann, Andreas; Worbe, Yulia

    2015-04-15

    Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. © 2015 International Parkinson and Movement Disorder Society.

  5. Brain cortical characteristics of lifetime cognitive ageing.

    Science.gov (United States)

    Cox, Simon R; Bastin, Mark E; Ritchie, Stuart J; Dickie, David Alexander; Liewald, Dave C; Muñoz Maniega, Susana; Redmond, Paul; Royle, Natalie A; Pattie, Alison; Valdés Hernández, Maria; Corley, Janie; Aribisala, Benjamin S; McIntosh, Andrew M; Wardlaw, Joanna M; Deary, Ian J

    2018-01-01

    Regional cortical brain volume is the product of surface area and thickness. These measures exhibit partially distinct trajectories of change across the brain's cortex in older age, but it is unclear which cortical characteristics at which loci are sensitive to cognitive ageing differences. We examine associations between change in intelligence from age 11 to 73 years and regional cortical volume, surface area, and thickness measured at age 73 years in 568 community-dwelling older adults, all born in 1936. A relative positive change in intelligence from 11 to 73 was associated with larger volume and surface area in selective frontal, temporal, parietal, and occipital regions (r cognitive ageing and a thinner cortex for any region. Interestingly, thickness and surface area were phenotypically independent across bilateral lateral temporal loci, whose surface area was significantly related to change in intelligence. These findings suggest that associations between regional cortical volume and cognitive ageing differences are predominantly driven by surface area rather than thickness among healthy older adults. Regional brain surface area has been relatively underexplored, and is a potentially informative biomarker for identifying determinants of cognitive ageing differences.

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

    Science.gov (United States)

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

    2014-12-09

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

  7. Functional neuroimaging of normal aging: Declining brain, adapting brain.

    Science.gov (United States)

    Sugiura, Motoaki

    2016-09-01

    Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Genomic integrity and the ageing brain.

    Science.gov (United States)

    Chow, Hei-man; Herrup, Karl

    2015-11-01

    DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

  9. Brain plasticity, memory, and aging: a discussion

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, E.L.; Rosenzweig, M.R.

    1977-12-01

    It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing for the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.

  10. Two hands, one brain, and aging.

    Science.gov (United States)

    Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

    2017-04-01

    Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD.

    Science.gov (United States)

    Burroni, L; Aucone, A M; Volterrani, D; Hayek, Y; Bertelli, P; Vella, A; Zappella, M; Vattimo, A

    1997-06-01

    Rett syndrome is a progressive neurological paediatric disorder associated with severe mental deficiency, which affects only girls. The aim of this study was to determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl-cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can explain the clinical manifestation and progression of the disease. Qualitative and quantitative global and regional brain blood flow was evaluated in 12 girls with Rett syndrome and compared with an aged-matched reference group of children. In comparison with the reference group, SPET revealed a considerable global reduction in cerebral perfusion in the groups of girls with Rett syndrome. A large statistical difference was noted, which was more evident when comparing the control group with girls with stage IV Rett syndrome than girls with stage III Rett syndrome. The reduction in cerebral perfusion reflects functional disturbance in the brain of children with Rett syndrome. These data confirm that 99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with Rett syndrome that may be associated with brain atrophy, even when magnetic resonance imaging appears normal.

  12. Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS.

    Science.gov (United States)

    Silva, Mauro Sb; Prescott, Melanie; Campbell, Rebecca E

    2018-04-05

    Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.

  13. The gender difference in the brain FDG distribution with aging

    International Nuclear Information System (INIS)

    Nakabeppu, Yoshiaki; Tanabe, Hiroaki; Jinguji, Megumi; Umanodan, Tomokazu; Nakajo, Masayuki; Nakajo, M.; Tateno, T.; Jinnouchi, S.

    2007-01-01

    The purpose of this study is to examine the change in brain fluorodeoxyglucose (FDG) distribution with aging. Subjects were 85 men and 116 women who had no mental abnormality and no evidence of cancer in the whole body FDG-positron emission tomography (PET) study for cancer checkup. The brain data were extracted from whole body data, and stratified according to the age: 30-39 (M: 10, F: 18), 40-49 (M: 11, F: 14), 50-59 (M: 10, F: 27), 60-64 (M: 11, F: 13), 65-69 (M: 11, F: 11), 70-74 (M: 11, F: 10), 75-79 (M: 13, F: 11), over 80 (M: 8, F: 12) years. Forties or more male and female stratified age groups were compared with each gender 30's age data using Statistical Parametric Mapping (SPM)2. In the man, the FDG activity of the bilateral temporal and frontal lobes decreased and the decreased domains were expanded with aging. But in the females, the decreased domains were complicated in 40-69 years old. Dynamic changes of sex hormones in the individual female menopause may affect the complicated results in the females. Further studies are needed to confirm it. (author)

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

    Science.gov (United States)

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

    2017-10-13

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

  15. Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging

    International Nuclear Information System (INIS)

    Ding, Xiao-Qi; Sun, Yimeng; Illies, Till; Zeumer, Hermann; Fiehler, Jens; Kruse, Bernd; Lanfermann, Heinrich

    2009-01-01

    Callosal fibres play an important role in psychomotor and cognitive functions. The purpose of this study was to investigate possible microstructural abnormalities of the corpus callosum in children with developmental delay, who have normal conventional brain MR imaging results. Seventeen pediatric patients (aged 1-9 years) with developmental delay were studied. Quantitative T2 and fractional anisotropy (FA) values were measured at the genu and splenium of the corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre density calculations of the CC were also carried out. The results were compared with those of the age-matched healthy subjects. A general elevation of T2 relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886 in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the CC were found only in patients older than 5 years. The study indicates that despite their inconspicuous findings in conventional MRI microstructural brain abnormalities are evident in these pediatric patients suffering from developmental delay. (orig.)

  16. Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

    Science.gov (United States)

    Bertolaccini, Maria Laura; Contento, Gregorio; Lennen, Ross; Sanna, Giovanni; Blower, Philip J; Ma, Michelle T; Sunassee, Kavitha; Girardi, Guillermina

    2016-12-01

    Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses. Although the antimalarial drug, hydroxychloroquine (HCQ) is increasingly used to treat pregnant women with APS, little is known about its efficacy and mechanism of action of HCQ. Because complement activation plays a crucial and causative role in placental ischemia and abnormal fetal brain development in APS we hypothesised that HCQ prevents these pregnancy complications through inhibition of complement activation. Using a mouse model of obstetric APS that closely resembles the clinical condition, we found that HCQ prevented fetal death and the placental metabolic changes -measured by proton magnetic resonance spectroscopy in APS-mice. Using 111 In labelled antiphospholipid antibodies (aPL) we identified the placenta and the fetal brain as the main organ targets in APS-mice. Using this same method, we found that HCQ does not inhibit aPL binding to tissues as was previously suggested from in vitro studies. While HCQ did not affect aPL binding to fetal brain it prevented fetal brain abnormal cortical development. HCQ prevented complement activation in vivo and in vitro. Complement C5a levels in serum samples from APS patients and APS-mice were lower after treatment with HCQ while the antibodies titres remained unchanged. HCQ prevented not only placental insufficiency but also abnormal fetal brain development in APS. By inhibiting complement activation, HCQ might also be an effective antithrombotic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Age- and Gene-Dosage–Dependent Cre-Induced Abnormalities in the Retinal Pigment Epithelium

    Science.gov (United States)

    He, Lizhi; Marioutina, Mariya; Dunaief, Joshua L.; Marneros, Alexander G.

    2015-01-01

    To conditionally inactivate genes in the retinal pigment epithelium (RPE) transgenic mouse strains have been developed, in which Cre recombinase (Cre) expression is driven by an RPE-specific gene promoter. The RPE is a quiescent epithelium, and continuous expression of Cre could affect its function. Here, we tested the hypothesis that continuous postnatal Cre expression in the RPE may lead to cellular abnormalities, which may depend on both age and Cre gene dosage. We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent RPE abnormalities were noticed, including attenuation of phalloidin and cytoplasmic active β-catenin staining, reduced cell size, and loss of the typical honeycomb pattern of RPE morphology in those RPE cells that stained for Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear abnormalities were observed already in young homozygous VMD2-Cre mice. Thus, continuous postnatal expression of Cre causes abnormalities in the RPE in an age- and Cre gene dosage-dependent manner, which needs to be considered in the interpretation of gene targeting studies in the RPE. PMID:24854863

  18. Structural brain abnormalities in first episode schizophrenia. Is it just illness?

    NARCIS (Netherlands)

    Rais, M.

    2011-01-01

    Although neuroimaging studies consistently demonstrated brain volume alterations in patients with schizophrenia, confounding factors like age, IQ, duration of the illness, use of antipsychotic medication and drug (ab-)use might partly explain these results. Therefore, the relation between

  19. Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function

    International Nuclear Information System (INIS)

    Barter, S.J.; Cunningham, D.A.; Lavender, J.P.; Gibellino, F.; Connellan, S.J.; Pride, N.B.

    1985-01-01

    The uniformity of regional ventilation during tidal breathing has been assessed using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established

  20. Ecology of the aging human brain.

    Science.gov (United States)

    Sonnen, Joshua A; Santa Cruz, Karen; Hemmy, Laura S; Woltjer, Randall; Leverenz, James B; Montine, Kathleen S; Jack, Clifford R; Kaye, Jeffrey; Lim, Kelvin; Larson, Eric B; White, Lon; Montine, Thomas J

    2011-08-01

    Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Autopsy study. Community- and population based. A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these, 6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.

  1. A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

    Science.gov (United States)

    Kil, Dries; De Vloo, Philippe; Fierens, Guy; Ceyssens, Frederik; Hunyadi, Borbála; Bertrand, Alexander; Nuttin, Bart; Puers, Robert

    2018-06-01

    Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

  2. Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Lv Han

    2014-01-01

    Full Text Available Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI technique. The present study used unilateral PT patients (n=42 and age-, sex-, and education-matched normal control subjects (n=42 to investigate the changes in structural and amplitude of low-frequency (ALFF of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients.

  3. Neuroimaging in aging: brain maintenance [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Lars Nyberg

    2017-07-01

    Full Text Available Neuroimaging studies of the aging brain provide support that the strongest predictor of preserved memory and cognition in older age is brain maintenance, or relative lack of brain pathology. Evidence for brain maintenance comes from different levels of examination, but up to now relatively few studies have used a longitudinal design. Examining factors that promote brain maintenance in aging is a critical task for the future and may be combined with the use of new techniques for multimodal imaging.

  4. How study of respiratory physiology aided our understanding of abnormal brain function in panic disorder.

    Science.gov (United States)

    Sinha, S; Papp, L A; Gorman, J M

    2000-12-01

    There is a substantial body of literature demonstrating that stimulation of respiration (hyperventilation) is a common event in panic disorder patients during panic attack episodes. Further, a number of abnormalities in respiration, such as enhanced CO2 sensitivity, have been detected in panic patients. This led some to posit that there is a fundamental abnormality in the physiological mechanisms that control breathing in panic disorder and that this abnormality is central to illness etiology. More recently, however, evidence has accumulated suggesting that respiratory physiology is normal in panic patients and that their tendency to hyperventilate and to react with panic to respiratory stimulants like CO2 represents the triggering of a hypersensitive fear network. The fear network anatomy is taken from preclinical studies that have identified the brain pathways that subserve the acquisition and maintenance of conditioned fear. Included are the amygdala and its brain stem projections, the hippocampus, and the medial prefrontal cortex. Although attempts to image this system in patients during panic attacks have been difficult, the theory that the fear network is operative and hyperactive in panic patients explains why both medication and psychosocial therapies are clearly effective. Studies of respiration in panic disorder are an excellent example of the way in which peripheral markers have guided researchers in developing a more complete picture of the neural events that occur in psychopathological states.

  5. Brain pathologies in extreme old age.

    Science.gov (United States)

    Neltner, Janna H; Abner, Erin L; Jicha, Gregory A; Schmitt, Frederick A; Patel, Ela; Poon, Leonard W; Marla, Gearing; Green, Robert C; Davey, Adam; Johnson, Mary Ann; Jazwinski, S Michal; Kim, Sangkyu; Davis, Daron; Woodard, John L; Kryscio, Richard J; Van Eldik, Linda J; Nelson, Peter T

    2016-01-01

    With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at the University of Kentucky Alzheimer's Disease Center, incorporating data from the Georgia Centenarian Study (n = 49 cases included), Nun Study (n = 17), and University of Kentucky Alzheimer's Disease Center (n = 11) cohorts. Average age of death was 102.0 (range: 98-107) years overall. Alzheimer's disease pathology was not universal (62% with "moderate" or "frequent" neuritic amyloid plaque densities), whereas frontotemporal lobar degeneration was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy) were observed in every case. Lewy body pathology was seen in 16.9% of subjects and hippocampal sclerosis of aging in 20.8%. We describe anatomic distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both hippocampal sclerosis of aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Divided attention and driving. The effects of aging and brain injury

    NARCIS (Netherlands)

    Withaar, Frederiec Kunna

    2000-01-01

    In this thesis, divided attention was investigated in four groups of subjects: closed head injury (CHI) patients, young control and healthy older subjects, and older subjects with cognitive impairments. It was studied how diffuse brain injury and normal and abnormal aging affect cognitive processes

  7. Analysis of abnormal findings observed on brain MRI T2 weighted image in a system for the detection of asymptomatic brain disease in 1,200 cases

    International Nuclear Information System (INIS)

    Horiguchi, Takashi; Yoshida, Kazunari; Sato, Syuzo; Kawase, Takeshi; Toya, Shigeo; Mizukami, Masahiro

    1998-01-01

    In this study we described the significance of asymptomatic cerebral infarction (ACI) and periventricular hyperintensity (PVH) observed on brain MRI in a system for detection of asymptomatic brain disease with 1,200 cases. The risk factors (RF), population in each age bracket of ACI and PVH, among groups with hypertension (HTG) and without RF (no-RFG), were investigated. The RF of ACI were hypertension (HT), diabetes mellitus (DM), and aging. Without DM, those are common RF of PVH. The population of PVH and ACI with PVH increased with aging in no-RFG. On the other hand, only the population of ACI with PVH increased with aging in HTG. The rate of these abnormal findings in HTG was significantly higher than that in no-RFG. In addition, HT accelerated the occurrence of these findings by 10-20 years. When patients were over 60 years old, ACI increased rapidly. Accordingly, we concluded that PVH and ACI had a common background. Long term follow up concerning the incidence of ACI in the group with only PVH was necessary. It was desirable that treatment for RF should be effected before the age of sixty. (author)

  8. Executive dysfunction, brain aging, and political leadership.

    Science.gov (United States)

    Fisher, Mark; Franklin, David L; Post, Jerrold M

    2014-01-01

    Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

  9. Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

    Science.gov (United States)

    Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

    2012-04-30

    Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Li, Ruili; Li, Hongjun [Capital Medical University, Department of Radiology, Beijing Youan Hospital, Beijing (China); Qiu, Bensheng [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Anhui Computer Application Institute of Traditional Chinese Medicine, Hefei, Anhui (China)

    2017-11-15

    It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

  12. Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

    International Nuclear Information System (INIS)

    Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan; Li, Ruili; Li, Hongjun; Qiu, Bensheng

    2017-01-01

    It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

  13. Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

    Science.gov (United States)

    Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

    2017-05-01

    Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

  14. Volumetric abnormalities of the brain in a rat model of recurrent headache.

    Science.gov (United States)

    Jia, Zhihua; Tang, Wenjing; Zhao, Dengfa; Hu, Guanqun; Li, Ruisheng; Yu, Shengyuan

    2018-01-01

    Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks' stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.

  15. Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yaou [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Liang Peipeng [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); International WIC institute, Beijing University of Technology, Beijing 100024 (China); Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong Huiqing; Ye Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li Kuncheng, E-mail: likuncheng1955@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2011-11-15

    Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

  16. Motor network plasticity and low-frequency oscillations abnormalities in patients with brain gliomas: a functional MRI study.

    Directory of Open Access Journals (Sweden)

    Chen Niu

    Full Text Available Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC and supplementary motor area (SMA. Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05. We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01-0.02 Hz; middle: 0.02-0.06 Hz; and high: 0.06-0.1 Hz, at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors.

  17. Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

    International Nuclear Information System (INIS)

    Liu Yaou; Liang Peipeng; Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen; Dong Huiqing; Ye Jing; Li Kuncheng

    2011-01-01

    Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

  18. Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction.

    Science.gov (United States)

    Illa, Miriam; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz-Moreno, Emma; Crispi, Fatima; Udina, Esther; Figueras, Francesc; Ginés, Silvia; Gratacós, Eduard

    2017-10-12

    The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR. © 2017 S. Karger AG, Basel.

  19. Impact of Aging Brain Circuits on Cognition

    Science.gov (United States)

    Samson, Rachel D.; Barnes, Carol A.

    2013-01-01

    Brain networks that engage the hippocampus and prefrontal cortex are central for enabling effective interactions with our environment. Some of the cognitive processes that these structures mediate, such as encoding and retrieving episodic experience, wayfinding, working memory and attention are known to be altered across the lifespan. As illustrated by examples given below, there is remarkable consistency across species in the pattern of age-related neural and cognitive change observed in healthy humans and other animals. These include changes in cognitive operations that are known to be dependent on the hippocampus, as well as those requiring intact prefrontal cortical circuits. Certain cognitive constructs that reflect the function of these areas lend themselves to investigation across species allowing brain mechanisms at different levels of analysis to be studied in greater depth. PMID:23773059

  20. High prevalence of abnormal motor repertoire at 3 months corrected age in extremely preterm infants.

    Science.gov (United States)

    Fjørtoft, Toril; Evensen, Kari Anne I; Øberg, Gunn Kristin; Songstad, Nils Thomas; Labori, Cathrine; Silberg, Inger Elisabeth; Loennecken, Marianne; Møinichen, Unn Inger; Vågen, Randi; Støen, Ragnhild; Adde, Lars

    2016-03-01

    To compare early motor repertoire between extremely preterm and term-born infants. An association between the motor repertoire and gestational age and birth weight was explored in extremely preterm infants without severe ultrasound abnormalities. In a multicentre study, the early motor repertoire of 82 infants born extremely preterm (ELGAN:<28 weeks) and/or with extremely low birth weight (ELBW:<1000 g) and 87 term-born infants were assessed by the "Assessment of Motor Repertoire - 2 to 5 Months" (AMR) which is part of Prechtl's "General Movement Assessment", at 12 weeks post-term age. Fidgety movements were classified as normal if present and abnormal if absent, sporadic or exaggerated. Concurrent motor repertoire was classified as normal if smooth and fluent and abnormal if monotonous, stiff, jerky and/or predominantly fast or slow. Eight-teen ELBW/ELGAN infants had abnormal fidgety movements (8 absent, 7 sporadic and 3 exaggerated fidgety movements) compared with 2 control infants (OR:12.0; 95%CI:2.7-53.4) and 46 ELBW/ELGAN infants had abnormal concurrent motor repertoire compared with 17 control infants (OR:5.3; 95%CI:2.6-10.5). Almost all detailed aspects of the AMR differed between the groups. Results were the same when three infants with severe ultrasound abnormalities were excluded. In the remaining ELBW/ELGAN infants, there was no association between motor repertoire and gestational age or birth weight. ELBW/ELGAN infants had poorer quality of early motor repertoire than term-born infants.The findings were not explained by severe abnormalities on neonatal ultrasound scans and were not correlated to the degree of prematurity. The consequences of these abnormal movement patterns remain to be seen in future follow-up studies. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  1. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    International Nuclear Information System (INIS)

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L.

    1990-01-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT

  2. Gender effects on age-related changes in brain structure.

    Science.gov (United States)

    Xu, J; Kobayashi, S; Yamaguchi, S; Iijima, K; Okada, K; Yamashita, K

    2000-01-01

    Previous reports have suggested that brain atrophy is associated with aging and that there are gender differences in brain atrophy with aging. These reports, however, neither exclude silent brain lesions in "healthy subjects" nor divide the brain into subregions. The aim of this study is to clarify the effect of gender on age-related changes in brain subregions by MR imaging. A computer-assisted system was used to calculate the brain matter area index (BMAI) of various regions of the brain from MR imaging of 331 subjects without brain lesions. There was significantly more brain atrophy with aging in the posterior parts of the right frontal lobe in male subjects than there was in female subjects. Age-related atrophy in the middle part of the right temporal lobe, the left basal ganglia, the parietal lobe, and the cerebellum also was found in male subjects, but not in female subjects. In the temporal lobe, thalamus, parieto-occipital lobe, and cerebellum, brain volume in the left hemisphere is significantly smaller than in the right hemisphere; sex and age did not affect the hemisphere differences of brain volume in these regions. The effect of gender on brain atrophy with aging varied in different subregions of the brain. There was more brain atrophy with aging in male subjects than in female subjects.

  3. Comparing CAT12 and VBM8 for Detecting Brain Morphological Abnormalities in Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Farnaz Farokhian

    2017-08-01

    Full Text Available The identification of the brain morphological alterations that play important roles in neurodegenerative/neurological diseases will contribute to our understanding of the causes of these diseases. Various automated software programs are designed to provide an automatic framework to detect brain morphological changes in structural magnetic resonance imaging (MRI data. A voxel-based morphometry (VBM analysis can also be used for the detection of brain volumetric abnormalities. Here, we compared gray matter (GM and white matter (WM abnormality results obtained by a VBM analysis using the Computational Anatomy Toolbox (CAT12 via the current version of Statistical Parametric Mapping software (SPM12 with the results obtained by a VBM analysis using the VBM8 toolbox implemented in the older software SPM8, in adult temporal lobe epilepsy (TLE patients with (n = 51 and without (n = 57 hippocampus sclerosis (HS, compared to healthy adult controls (n = 28. The VBM analysis using CAT12 showed that compared to the healthy controls, significant GM and WM reductions were located in ipsilateral mesial temporal lobes in the TLE-HS patients, and slight GM amygdala swelling was present in the right TLE-no patients (n = 27. In contrast, the VBM analysis via the VBM8 toolbox showed significant GM and WM reductions only in the left TLE-HS patients (n = 25 compared to the healthy controls. Our findings thus demonstrate that compared to VBM8, a VBM analysis using CAT12 provides a more accurate volumetric analysis of the brain regions in TLE. Our results further indicate that a VBM analysis using CAT12 is more robust and accurate against volumetric alterations than the VBM8 toolbox.

  4. Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

    Science.gov (United States)

    Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2014-05-01

    Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel

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

    Science.gov (United States)

    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. Published by Elsevier B.V.

  6. Harvard Aging Brain Study: Dataset and accessibility.

    Science.gov (United States)

    Dagley, Alexander; LaPoint, Molly; Huijbers, Willem; Hedden, Trey; McLaren, Donald G; Chatwal, Jasmeer P; Papp, Kathryn V; Amariglio, Rebecca E; Blacker, Deborah; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Schultz, Aaron P

    2017-01-01

    The Harvard Aging Brain Study is sharing its data with the global research community. The longitudinal dataset consists of a 284-subject cohort with the following modalities acquired: demographics, clinical assessment, comprehensive neuropsychological testing, clinical biomarkers, and neuroimaging. To promote more extensive analyses, imaging data was designed to be compatible with other publicly available datasets. A cloud-based system enables access to interested researchers with blinded data available contingent upon completion of a data usage agreement and administrative approval. Data collection is ongoing and currently in its fifth year. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Dystrophic microglia in the aging human brain.

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    Streit, Wolfgang J; Sammons, Nicole W; Kuhns, Amanda J; Sparks, D Larry

    2004-01-15

    We have studied microglial morphology in the human cerebral cortex of two nondemented subjects using high-resolution LN-3 immunohistochemistry. Several abnormalities in microglial cytoplasmic structure, including deramification, spheroid formation, gnarling, and fragmentation of processes, were identified. These changes were determined to be different from the morphological changes that occur during microglial activation and they were designated collectively as microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia revealed that these were much more prevalent in the older subject (68-year-old) than in the younger one (38-year-old). Thus, we conclude that microglial dystrophy is a sign of microglial cell senescence. We hypothesize that microglial senescence could be important for understanding age-related declines in cognitive function. Copyright 2003 Wiley-Liss, Inc.

  8. Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia

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    Ganeshan, Balaji [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Miles, Kenneth A.; Critchley, Hugo D. [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); Young, Rupert C.D.; Chatwin, Christopher R. [University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Gurling, Hugh M.D. [University College London, Department of Mental Health Sciences, London (United Kingdom)

    2010-04-15

    Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes. (orig.)

  9. Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia

    International Nuclear Information System (INIS)

    Ganeshan, Balaji; Miles, Kenneth A.; Critchley, Hugo D.; Young, Rupert C.D.; Chatwin, Christopher R.; Gurling, Hugh M.D.

    2010-01-01

    Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes. (orig.)

  10. Abnormal brain activation during threatening face processing in schizophrenia: A meta-analysis of functional neuroimaging studies.

    Science.gov (United States)

    Dong, Debo; Wang, Yulin; Jia, Xiaoyan; Li, Yingjia; Chang, Xuebin; Vandekerckhove, Marie; Luo, Cheng; Yao, Dezhong

    2017-11-15

    Impairment of face perception in schizophrenia is a core aspect of social cognitive dysfunction. This impairment is particularly marked in threatening face processing. Identifying reliable neural correlates of the impairment of threatening face processing is crucial for targeting more effective treatments. However, neuroimaging studies have not yet obtained robust conclusions. Through comprehensive literature search, twenty-one whole brain datasets were included in this meta-analysis. Using seed-based d-Mapping, in this voxel-based meta-analysis, we aimed to: 1) establish the most consistent brain dysfunctions related to threating face processing in schizophrenia; 2) address task-type heterogeneity in this impairment; 3) explore the effect of potential demographic or clinical moderator variables on this impairment. Main meta-analysis indicated that patients with chronic schizophrenia demonstrated attenuated activations in limbic emotional system along with compensatory over-activation in medial prefrontal cortex (MPFC) during threatening faces processing. Sub-task analyses revealed under-activations in right amygdala and left fusiform gyrus in both implicit and explicit tasks. The remaining clusters were found to be differently involved in different types of tasks. Moreover, meta-regression analyses showed brain abnormalities in schizophrenia were partly modulated by age, gender, medication and severity of symptoms. Our results highlighted breakdowns in limbic-MPFC circuit in schizophrenia, suggesting general inability to coordinate and contextualize salient threat stimuli. These findings provide potential targets for neurotherapeutic and pharmacological interventions for schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Brain Age in Early Stages of Bipolar Disorders or Schizophrenia.

    Science.gov (United States)

    Hajek, Tomas; Franke, Katja; Kolenic, Marian; Capkova, Jana; Matejka, Martin; Propper, Lukas; Uher, Rudolf; Stopkova, Pavla; Novak, Tomas; Paus, Tomas; Kopecek, Miloslav; Spaniel, Filip; Alda, Martin

    2017-12-20

    The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

  12. Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

    Science.gov (United States)

    Tang, Chris C; Eidelberg, David

    2010-01-01

    Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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    Nobuyuki eTakei

    2014-04-01

    Full Text Available 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 mTOR (mammalian TOR. 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 (CNS, 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.

  14. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  15. Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

    Science.gov (United States)

    Kronbichler, Lisa; Tschernegg, Melanie; Martin, Anna Isabel; Schurz, Matthias; Kronbichler, Martin

    2017-10-21

    Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  16. The nature of white matter abnormalities in blast-related mild traumatic brain injury

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    Jasmeet P. Hayes

    2015-01-01

    Full Text Available Blast-related traumatic brain injury (TBI has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI. The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC group, and blast-related mTBI with LOC (mTBI + LOC group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1 a region-specific analysis and 2 a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of

  17. Basic abnormalities in visual processing affect face processing at an early age in autism spectrum disorder.

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    Vlamings, Petra Hendrika Johanna Maria; Jonkman, Lisa Marthe; van Daalen, Emma; van der Gaag, Rutger Jan; Kemner, Chantal

    2010-12-15

    A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Age-related and 224Ra-induced abnormalities in the teeth of male mice

    International Nuclear Information System (INIS)

    Humphreys, E.R.; Stones, V.A.

    1985-01-01

    A high incidence of incisor abnormalities was found in aged control and aged 224 Ra-treated male CBA mice. Visual examination of the abnormalities in both controls and treated mice revealed extreme shortening of the upper incisors and hypoplastic, grooved or undulating enamel. The administration of 865 or 1730 nCi of 224 Ra hastened the onset of incisor abnormalities although no specific feature was attributable solely to radium toxicity. Radiography and histology revealed corrugated incisors, obliteration of the pulp cavity, extension and disorganized growth of incisors basally, secondary incisors, open pulp and fractures within the alveoli. There was a statistically-significant reduction in the number of molars present in animals given 432, 865 or 1730 nCi 224 Ra. (author)

  19. Changes of FDG brain uptake in patients with abnormal thyroid function

    International Nuclear Information System (INIS)

    Huang, Wen-Sheng; Chang, Chih-Yung; Cheng, Cheng Yi

    2009-01-01

    Full text: Objective: To investigate FOG brain uptake in patients with hypo- and subclinical hyperthyroidism undergoing whole-body FOG PET/CT. Methods: Sixty-four patients who had received total thyroidectomy for thyroid carcinoma underwent whole-body FDG PETI CT. Thirty-two of them received imaging in subclinical hyperthyroid status (15 males; 17 females; mean age, 55 ± 14 years) while the other 32 age-matched patients underwent the scan 4 wk after thyroid hormone withdrawal (12 males; 20 females; mean age, 56 ± 13 years). Brain images were performed I h after 370 MBq intravenous injection using a dedicated PET/CT (Siemens Biograph BGO duo). FOG-uptake was quantified by the standardized uptake value (SUY), normalized to patient's body weight. The volume of brain was determined by PET with 40% maximum SUY threshold. The brain mean SUV (SUY mean) were calculated in each patient. Data were compared between the two groups. Results: The brain mean SUYs for the hypothyroid patients ranged between 3.11 and 6.35 (averaged SUY mean 5.13 ± 0.91) while those of the subclinical hyperthyroid patients varied from 3.53 to 8.29 (mean SUY mean 5.77 ± 1.04). There was a significant global reduction of brain FDG uptake in the hypothyroid group (II.] %, P < 0.0 I) but no significant changes in the sub-clinical hyperthyroid group compared to the controls. Conclusion: FDG brain uptake in subclinical hyperthyroid patients was significantly greater than that of patients with hypothyroidism, suggesting effects of thyroid hormone on cerebral glucose metabolism.

  20. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    Science.gov (United States)

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  1. Abnormalities of Functional Brain Networks in Pathological Gambling: A Graph-Theoretical Approach

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    Melanie eTschernegg

    2013-09-01

    Full Text Available Functional neuroimaging studies of pathological gambling demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in pathological gambling. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional MRI data in pathological gambling. We compared 19 patients with pathological gambling to 19 healthy controls using the Graph Analysis Toolbox (GAT. None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (SMA, reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients.These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that pathological gambling is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in pathological gambling cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders.

  2. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    Science.gov (United States)

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images. Methods 3D T1-weighted brain MRIs of 41 WS subjects (age: 29.2±9.2SD years; 23F/18M) and 39 age-matched healthy controls (age: 27.5±7.4 years; 23F/16M) were fluidly registered to a minimum deformation target. Fine-scale volumetric differences were mapped between diagnostic groups. Local regions were identified where regional structure volumes were associated with diagnosis, and with intelligence quotient (IQ) scores. Brain asymmetry was also mapped and compared between diagnostic groups. Results WS subjects exhibited widely distributed brain volume reductions (~10–15% reduction; P < 0.0002, permutation test). After adjusting for total brain volume, the frontal lobes, anterior cingulate, superior temporal gyrus, amygdala, fusiform gyrus and cerebellum were found to be relatively preserved in WS, but parietal and occipital lobes, thalamus and basal ganglia, and midbrain were disproportionally decreased in volume (P < 0.0002). These regional volumes also correlated positively with performance IQ in adult WS subjects (age ≥ 30 years, P = 0.038). Conclusion TBM facilitates 3D visualization of brain volume reductions in WS. Reduced parietal/occipital volumes may be associated with visuospatial deficits in WS. By contrast, frontal lobes, amygdala, and cingulate gyrus are relatively preserved or even enlarged, consistent with unusual affect regulation and language production in WS. PMID:17512756

  3. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

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    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  4. THE TIME COURSE OF ABNORMALITIES IN THE BRAIN SUBCORTICAL VISUAL CENTRE FOLLOWING EARLY IMPAIRMENT OF BINOCULAR EXPERIENCE

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    S. V. Alekseenko

    2016-01-01

    Full Text Available Background: Amblyopia related to congenital strabismus belongs to neurological disorders since it is caused by structural and functional remodeling of the visual parts of the brain without any baseline retinal pathology. Although a large number of animal studies on experimentally induced strabismus, as well as clinical cases have been published, the mechanisms and time course of the processes within the brain structures are not fully understood. Aim: To study the time course of abnormalities in the dorsal lateral geniculate nucleus (LGNd in animals with surgically induced convergent strabismus. LGNd is the structure through which the information from the retina goes to the visual cortex separately for each eye. Materials and methods: 14 strabismic and 17 intact kittens of four age groups were studied. Histochemical method was used to identify cytochrome oxidase which is a  mitochondrial respiratory chain enzyme whose activity correlates with neuronal functional activity. Optical density in eye-specific layers  A  and A1 was measured on the images of stained LGNd sections, with calculation of the contrast difference between them. Results: In strabismic kittens, there were changes in activity of A and A1 layers in the projection of the central part of visual field in LGNd of both hemispheres. At early stages of their formation, a relative decrease in activity was found in both hemispheres in the LGNd layers innervated through non-crossed pathways from both retinae. Thereafter, the time course of abnormalities in LGNd of both hemispheres was different. In the hemisphere ipsilateral to the squinting eye, the difference in layer activity was highest at the age from 3 to 5 months. However, in the opposite hemisphere the same difference indicating a decreased activity in the layer of the squinting eye were observed only at the age of 5 months. Conclusion: The process of amblyopia development during congenital convergent strabismus is

  5. Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights into Altered Brain Maturation

    Science.gov (United States)

    Morton, Paul D.; Ishibashi, Nobuyuki; Jonas, Richard A.

    2017-01-01

    In the past two decades it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however the underlying etiologies remain largely unknown and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential in order to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD. PMID:28302742

  6. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2016-01-01

    Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  7. Abnormal small-world brain functional networks in obsessive-compulsive disorder patients with poor insight.

    Science.gov (United States)

    Lei, Hui; Cui, Yan; Fan, Jie; Zhang, Xiaocui; Zhong, Mingtian; Yi, Jinyao; Cai, Lin; Yao, Dezhong; Zhu, Xiongzhao

    2017-09-01

    There are limited data on neurobiological correlates of poor insight in obsessive-compulsive disorder (OCD). This study explored whether specific changes occur in small-world network (SWN) properties in the brain functional network of OCD patients with poor insight. Resting-state electroencephalograms (EEGs) were recorded for 12 medication-free OCD patients with poor insight, 50 medication-free OCD patients with good insight, and 36 healthy controls. Both of the OCD groups exhibited topological alterations in the brain functional network characterized by abnormal small-world parameters at the beta band. However, the alterations at the theta band only existed in the OCD patients with poor insight. A relatively small sample size. Subjects were naïve to medications and those with Axis I comorbidity were excluded, perhaps limiting generalizability. Disrupted functional integrity at the beta bands of the brain functional network may be related to OCD, while disrupted functional integrity at the theta band may be associated with poor insight in OCD patients, thus this study might provide novel insight into our understanding of the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

    Science.gov (United States)

    Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

    2008-10-14

    Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

  9. Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study.

    Science.gov (United States)

    Tian, Lin; Meng, Chun; Jiang, Ying; Tang, Qunfeng; Wang, Shuai; Xie, Xiyao; Fu, Xiangshuai; Jin, Chunhui; Zhang, Fuquan; Wang, Jidong

    2016-04-03

    Abnormal brain networks have been observed in patients with obsessive-compulsive disorder (OCD). However, detailed network hub and connectivity changes remained unclear in treatment-naive patients with OCD. Here, we sought to determine whether patients show hub-related connectivity changes in their whole-brain functional networks. We used resting-state functional magnetic resonance imaging data and voxel-based graph-theoretic analysis to investigate functional connectivity strength and hubs of whole-brain networks in 29 treatment-naive patients with OCD and 29 age- and gender-matched healthy controls. Correlation analysis was applied for potential associations with OCD symptom severity. OCD selectively targeted brain regions of higher functional connectivity strength than the average including brain network hubs, mainly distributed in the cortico-striato-thalamo-cortical (CSTC) circuits and additionally parietal, occipital, temporal and cerebellar regions. Moreover, affected functional connectivity strength in the cerebellum, the medial orbitofrontal cortex and superior occipital cortex was significantly associated with global OCD symptom severity. Our results provide the evidence about OCD-related brain network hub changes, not only in the CSTC circuits but more distributed in whole brain networks. Data suggest that whole brain network hub analysis is useful for understanding the pathophysiology of OCD. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Age Specific Cytological Abnormalities in Women Screened for Cervical Cancer in the Emirate of Abu Dhabi.

    Science.gov (United States)

    Al Zaabi, Muna; Al Muqbali, Shaikha; Al Sayadi, Thekra; Al Ameeri, Suhaila; Coetsee, Karin; Balayah, Zuhur; Ortashi, Osman

    2015-01-01

    Cervical cancer is the second most common cancer in women worldwide, with about 500,000 new cases and 270,000 deaths each year. Globally, it is estimated that over one million women currently have cervical cancer, most of whom have not been diagnosed, or have no access to treatment that could cure them or prolong their lives. In the United Arab Emirates (UAE) cervical cancer is the third most common cancer in women. A population-based cross-sectional retrospective survey of cervical smear abnormalities was conducted in the Emirate of Abu Dhabi, UAE, from January 2013 to December 2013 by collecting consecutive liquid-based cytology samples from the Department of Pathology at the SKMC Hospital in Abu Dhabi city. The total number of women screened for cervical cancer for the year 2013 at SKMC was 4,593, with 225 (4.89%) abnormal smears. The majority of the abnormal smear results were atypical squamous cells of undetermined significance (ASCUS) 114 (2.48%). This study showed 60% increase in the rate of abnormal cervical smears in the UAE over the last 10 years. In this study the highest incidence of high grade abnormalities were seen in women above the age of 61 years (1.73%), this might be due to the fact that this group of women missed the chance of screening of cervical cancer earlier in their lives or could be explained by the well-known second peak of HPV infection seen in many prevalence studies. We conclude that the rate of abnormal cervical smear in the screened Abu Dhabi women is not different from the rate in developed countries. A notable increase in both low and high grade abnormalities has occurred within the last decade.

  11. Psychological stress exposure to aged mice causes abnormal feeding patterns with changes in the bout number.

    Science.gov (United States)

    Yamada, Chihiro; Mogami, Sachiko; Hattori, Tomohisa

    2017-11-09

    Stress responses are affected by aging. However, studies on stress-related changes in feeding patterns with aging subject are minimal. We investigated feeding patterns induced by two psychological stress models, revealing characteristics of stress-induced feeding patterns as "meal" and "bout" (defined as the minimum feeding behavior parameters) in aged mice. Feeding behaviors of C57BL/6J mice were monitored for 24 h by an automatic monitoring device. Novelty stress reduced the meal amount over the 24 h in both young and aged mice, but as a result of a time course study it was persistent in aged mice. In addition, the decreased bout number was more pronounced in aged mice than in young mice. The 24-h meal and bout parameters did not change in either the young or aged mice following water avoidance stress (WAS). However, the meal amount and bout number increased in aged mice for 0-6 h after WAS exposure but remained unchanged in young mice. Our findings suggest that changes in bout number may lead to abnormal stress-related feeding patterns and may be one tool for evaluating eating abnormality in aged mice.

  12. White matter lesions of the aging brain visualized on MRI

    International Nuclear Information System (INIS)

    Tomura, Noriaki; Shindou, Masaaki; Hashimoto, Manabu; Kato, Toshio; Monma, Keiji; Segawa, Yasuhiko.

    1990-01-01

    The purpose of this report is to study the relationship between the severity of the white matter lesions (WMLs) and aging. We reviewed 215 subjects (11-88 years of age) referred for MR imaging performed between June 1988 and August 1989 on a 0.5T superconducting MR imager. The spin echo technique of image acquisition was used, with TR 1800 ms and TE 120 ms. All subjects were free from neurological abnormalities. The patterns of MR imaging of the incidental WMLs were divided into four grades; grades 0-3 (grade 0, no lesions; grade 1, lesions confined to one lobe; grade 2, lesions beyond one lobe; grade 3, confluent periventricular lesions). We investigated the relationships among the prevalence of WMLs, the grading of WMLs, age, and hypertension. Furthermore, we analyzed the grading of WMLs in relation to the degree of brain atrophy (bicaudate index) and the prevalence of basal ganglionic lesions. The mean age of grade 0 (n=90), grade 1 (n=36), grade 2 (n=58) and grade 3 (n=31) was 43.4±13.2, 57.3±7.3, 63.5±10.8 and 71.6±8.5. The statistical difference of age between grade 0 and 1 (p 160 mmHg) showed higher grading of WMLs than other subjects. There was a statistical difference in the bicaudate index between grade 0 and 2 (p<0.001), and grade 0 and 3 (p<0.001). Of the 89 subjects of grade 2 or 3, 47 (53%) had basal ganglionic and/or thalamic lesions. It was confirmed that WMLs of neurologically healthy subjects significantly correlated with aging. In addition, hypertension accelerated WMLs. (author)

  13. Abnormal expression of ephrin-A5 affects brain development of congenital hypothyroidism rats.

    Science.gov (United States)

    Suo, Guihai; Shen, Feifei; Sun, Baolan; Song, Honghua; Xu, Meiyu; Wu, Youjia

    2018-05-14

    EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.

  14. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  15. Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

    Science.gov (United States)

    Carnero Contentti, Edgar; Daccach Marques, Vanessa; Soto de Castillo, Ibis; Tkachuk, Veronica; Antunes Barreira, Amilton; Armas, Elizabeth; Chiganer, Edson; de Aquino Cruz, Camila; Di Pace, José Luis; Hryb, Javier Pablo; Lavigne Moreira, Carolina; Lessa, Carmen; Molina, Omaira; Perassolo, Monica; Soto, Arnoldo; Caride, Alejandro

    2018-01-01

    Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. Typical brain MRI abnormalities are frequent in NMOSD at disease onset. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    Science.gov (United States)

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  17. Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome.

    Science.gov (United States)

    Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

    2013-10-22

    Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.

  18. Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis.

    LENUS (Irish Health Repository)

    Morgan, K D

    2010-07-01

    African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients.

  19. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

    Directory of Open Access Journals (Sweden)

    Fuka Aizawa

    2016-12-01

    Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

  20. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

    Science.gov (United States)

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

    2016-12-01

    The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  1. Probability of an Abnormal Screening PSA Result Based on Age, Race, and PSA Threshold

    Science.gov (United States)

    Espaldon, Roxanne; Kirby, Katharine A.; Fung, Kathy Z.; Hoffman, Richard M.; Powell, Adam A.; Freedland, Stephen J.; Walter, Louise C.

    2014-01-01

    Objective To determine the distribution of screening PSA values in older men and how different PSA thresholds affect the proportion of white, black, and Latino men who would have an abnormal screening result across advancing age groups. Methods We used linked national VA and Medicare data to determine the value of the first screening PSA test (ng/mL) of 327,284 men age 65+ who underwent PSA screening in the VA healthcare system in 2003. We calculated the proportion of men with an abnormal PSA result based on age, race, and common PSA thresholds. Results Among men age 65+, 8.4% had a PSA >4.0ng/mL. The percentage of men with a PSA >4.0ng/mL increased with age and was highest in black men (13.8%) versus white (8.0%) or Latino men (10.0%) (PPSA >4.0ng/mL ranged from 5.1% of Latino men age 65–69 to 27.4% of black men age 85+. Raising the PSA threshold from >4.0ng/mL to >10.0ng/mL, reclassified the greatest percentage of black men age 85+ (18.3% absolute change) and the lowest percentage of Latino men age 65–69 (4.8% absolute change) as being under the biopsy threshold (PPSA threshold together affect the pre-test probability of an abnormal screening PSA result. Based on screening PSA distributions, stopping screening among men whose PSA 10ng/ml has the greatest effect on reducing the number of older black men who will face biopsy decisions after screening. PMID:24439009

  2. Quantitative Machine Learning Analysis of Brain MRI Morphology throughout Aging.

    Science.gov (United States)

    Shamir, Lior; Long, Joe

    2016-01-01

    While cognition is clearly affected by aging, it is unclear whether the process of brain aging is driven solely by accumulation of environmental damage, or involves biological pathways. We applied quantitative image analysis to profile the alteration of brain tissues during aging. A dataset of 463 brain MRI images taken from a cohort of 416 subjects was analyzed using a large set of low-level numerical image content descriptors computed from the entire brain MRI images. The correlation between the numerical image content descriptors and the age was computed, and the alterations of the brain tissues during aging were quantified and profiled using machine learning. The comprehensive set of global image content descriptors provides high Pearson correlation of ~0.9822 with the chronological age, indicating that the machine learning analysis of global features is sensitive to the age of the subjects. Profiling of the predicted age shows several periods of mild changes, separated by shorter periods of more rapid alterations. The periods with the most rapid changes were around the age of 55, and around the age of 65. The results show that the process of brain aging of is not linear, and exhibit short periods of rapid aging separated by periods of milder change. These results are in agreement with patterns observed in cognitive decline, mental health status, and general human aging, suggesting that brain aging might not be driven solely by accumulation of environmental damage. Code and data used in the experiments are publicly available.

  3. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, F M; Magon, S

    2015-01-01

    if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate...... resting-state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging. METHODS: Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine......, and in a data-driven exploratory fashion (dual regression) in order to reveal any possible between-group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables. RESULTS: No differences of functional connectivity were found between patients...

  5. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    International Nuclear Information System (INIS)

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-01-01

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  6. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

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

    Science.gov (United States)

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

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Central region morphometry in a child brain; Age and gender ...

    African Journals Online (AJOL)

    2013-10-10

    Oct 10, 2013 ... Background: Data on central region morphometry of a child brain is important not only in terms of ... brain volume reaches the peak at the age of 14.5 in men ..... child and adolescent brain and effects of genetic variation.

  9. Prevalence of triangular fibrocartilage complex abnormalities regardless of symptoms rise with age: systematic review and pooled analysis.

    Science.gov (United States)

    Chan, Jimmy J; Teunis, Teun; Ring, David

    2014-12-01

    Triangular fibrocartilage complex abnormalities seem to be more common with age, but the degree to which this is so, and the degree to which the presence of an abnormality is associated with symptoms, are topics of controversy. We wished to perform a systematic review to determine the prevalence of triangular fibrocartilage complex abnormalities, and to determine if the prevalence of abnormalities are greater with increasing age. In addition, we stratified age groups based on symptoms. We searched MEDLINE, EMBASE, and the Cochrane Library through August 15, 2013. Studies that reported triangular fibrocartilage complex abnormalities by age were included. Fifteen studies including 977 wrists met our criteria and reported a total of 368 (38%) triangular fibrocartilage complex abnormalities. Eight studies included symptomatic patients; the remainder studied cadavers (six studies) or asymptomatic volunteers (one study). Patients were divided into four age groups (fibrocartilage complex abnormalities increased with age, from 27% (80/301) in patients younger than 30 years to 49% (130/265) in patients 70 years and older (p fibrocartilage complex prevalence abnormality increased from 15% (24/159) to 49% (129/263) in the same age groups (p fibrocartilage complex abnormalities are common in symptomatic and asymptomatic wrists, and they are increasingly common with age. As in all situations where abnormalities are so common that they may be incidental, we need (1) a reliable and accurate method for determining whether these abnormalities are the cause of symptoms; and (2) evidence that treatment of these abnormalities improves symptoms better than placebo. Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

  10. Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years.

    Science.gov (United States)

    Rosario, Pedro Weslley

    2008-12-01

    The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women with SCH showed a significant increase in serum markers of bone formation and resorption. In addition, bone mineral density (BMD) was lower in the femoral neck but not in the lumbar spine in patients before menopause, whereas a lower BMD was observed at both sites in postmenopausal patients. SCH is not completely asymptomatic in women aged < 65 years, and is associated with heart abnormalities and with increased bone turnover and reduced BMD even before menopause.

  11. What is ''normal aging brain for his/her age'' ? The first report

    International Nuclear Information System (INIS)

    Taki, Yasuyuki; Kinomura, Shigeo; Goto, Ryoi

    2005-01-01

    We evaluated the correlations between the gray matter volume, white matter volume and age, and determined normal aging brain for his/her age in every decade. We analyzed magnetic resonance images of the brain from 828 normal Japanese subjects. Significant negative correlation between the gray matter ratio (ratio of the gray matter volume in intracranial volume) and age was shown. From these results, we determined ''normal aging brain for his/her age'' and ''atrophied brain for his/her age'' in every decade. (author)

  12. Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years

    OpenAIRE

    Rosario, Pedro Weslley

    2008-01-01

    The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged < 65 years. Forty-eight women with SCH were evaluated. The control group consisted of 48 euthyroid volunteers. The mean symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women wit...

  13. Divided attention and driving. The effects of aging and brain injury

    OpenAIRE

    Withaar, Frederiec Kunna

    2000-01-01

    In this thesis, divided attention was investigated in four groups of subjects: closed head injury (CHI) patients, young control and healthy older subjects, and older subjects with cognitive impairments. It was studied how diffuse brain injury and normal and abnormal aging affect cognitive processes involved in divided attention tasks. Furthermore, it was investigated how deficits in divided attention relate to performance of instrumental activities of daily living (IADL), with an emphasis on ...

  14. Social support, stress and the aging brain.

    Science.gov (United States)

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Age-and Brain Region-Specific Differences in Mitochondrial ...

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  16. Radiopharmaceuticals for the imaging of functional abnormalities of the developing brain

    International Nuclear Information System (INIS)

    Senekowitsch, R.; Kriegel, H.

    1986-01-01

    The measurement of physiological parameters in man is possible with the help of positron emission tomography (PET) and radiopharmaceuticals labeled with short lived positron emitters as C 11, N 13, O 15 and F 18. With the use of this substances it is possible to make a tomographic map defining regional metabolic parameters in normal and diseased brain. This technique has therefore also be named 'in vivo autoradiography'. The possibility of applying C 11 or F 18 labeled deoxyglucose with PET for detecting regional and local changes in cerebral metabolic rate of glucose in brain development in children of 5 days to 1 year of age is discussed. Beyond this a relationship between cerebral metabolic rate of glucose, cerebral blood flow and cerebral metabolic rate of oxygen by use of this technique after inhalation of O 15 and C 11-labeled CO 2 is shown. Attention is drawn to the application of C 11-methyl-spiperone and PET to visualize dopamine receptor density in the brain. The receptor density and the ability of receptors to bind neutrotransmitters is found to be influenced by prenatal irradiation. It is expected that relations between alterations in the developing brain and its postnatal function may be explored in this way. (orig.)

  17. Adolescent binge drinking linked to abnormal spatial working memory brain activation: differential gender effects.

    Science.gov (United States)

    Squeglia, Lindsay M; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F

    2011-10-01

    Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Forty binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males), aged 16 to 19 years, completed neuropsychological testing, substance use interviews, and an SWM task during functional magnetic resonance imaging. Significant binge drinking status × gender interactions were found (p working memory performances (p performance (p gender-specific differences in frontal, temporal, and cerebellar brain activation during an SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that blood oxygen level-dependent activation is affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive marker of alcohol impact to the brain on future behaviors, such as driving safety, academic performance, and neuropsychological performance. Copyright © 2011 by the Research Society on Alcoholism.

  18. HYSTEROSCOPIC EVALUATION OF WOMEN IN REPRODUCTIVE AGE GROUP WITH ABNORMAL UTERINE BLEEDING

    Directory of Open Access Journals (Sweden)

    E. Vanaja Reddy

    2016-10-01

    Full Text Available BACKGROUND Abnormal uterine bleeding is the most common complaint in gynaecology and an important source of morbidity. This study evaluates the usefulness of hysteroscopy in the diagnosis of abnormal uterine bleeding in comparison to dilatation and curettage in reproductive age group. MATERIALS AND METHODS Between September 2011 to July 2013, women with AUB attending Gynaec OP were subjected to hysteroscopy and subsequent dilatation and curettage. Data was collected and analysed. RESULTS AUB was more common in 30-34 yrs. The most common presenting complaint was menorrhagia. Normal hysteroscopic view was seen in 50% cases. Abnormalities seen were endometrial hyperplasia, polyps, submucous myoma synechiae and rue. Both hysteroscopy and curettage gave specificity of 70%, but the ability to diagnose focal lesion (sensitivity was more with hysteroscopy in comparison to curettage 70 vis. 36. 43 patients had the same tissue diagnosis in both hysteroscopy and curettage. Hysteroscopy revealed more information than curettage in 42% and curettage had more information in 15% cases, 100% accuracy was seen in case of myoma, IUCD, adhesions and polyps with hysteroscopy. CONCLUSION This study confirms the conclusion of many others that hysteroscopy is superior to dilatation and curettage in evaluating patients with abnormal uterine bleeding.

  19. Brain abnormalities on MRI in non-functioning pituitary adenoma patients treated with or without postoperative radiotherapy

    NARCIS (Netherlands)

    Sattler, Margriet G. A.; Meiners, Linda C.; Sluiter, Wim J.; van den Berg, Gerrit; Langendijk, Johannes A.; Wolffenbuttel, Bruce H. R.; van den Bergh, Alphons C. M.; van Beek, Andre P.

    Background and purpose: To assess and compare brain abnormalities on Magnetic Resonance Imaging (MRI) in non-functioning pituitary macro-adenoma (NFA) patients treated with or without postoperative radiotherapy (RT). Material and methods: In 86 NFA patients, treated between 1987 and 2008 at the

  20. Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

    2016-02-01

    A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

  1. N-Terminal pro-Brain Natriuretic Peptide and Associations With Brain Magnetic Resonance Imaging (MRI Features in Middle Age: The CARDIA Brain MRI Study

    Directory of Open Access Journals (Sweden)

    Ian T. Ferguson

    2018-05-01

    Full Text Available ObjectiveAs part of research on the heart–brain axis, we investigated the association of N-terminal pro-brain natriuretic peptide (NT-proBNP with brain structure and function in a community-based cohort of middle-aged adults from the Brain Magnetic Resonance Imaging sub-study of the Coronary Artery Risk Development in Young Adults (CARDIA Study.Approach and resultsIn a cohort of 634 community-dwelling adults with a mean (range age of 50.4 (46–52 years, we examined the cross-sectional association of NT-proBNP to total, gray (GM and white matter (WM volumes, abnormal WM load and WM integrity, and to cognitive function tests [the Digit Symbol Substitution Test (DSST, the Stroop test, and the Rey Auditory–Verbal Learning Test]. These associations were examined using linear regression models adjusted for demographic and cardiovascular risk factors and cardiac output. Higher NT-proBNP concentration was significantly associated with smaller GM volume (β = −3.44; 95% CI = −5.32, −0.53; p = 0.003, even after additionally adjusting for cardiac output (β = −2.93; 95% CI = −5.32, −0.53; p = 0.017. Higher NT-proBNP levels were also associated with lower DSST scores. NT-proBNP was not related to WM volume, WM integrity, or abnormal WM load.ConclusionIn this middle-aged cohort, subclinical levels of NT-proBNP were related to brain function and specifically to GM and not WM measures, extending similar findings in older cohorts. Further research is warranted into biomarkers of cardiac dysfunction as a target for early markers of a brain at risk.

  2. Lower cognitive reserve in the aging human immunodeficiency virus-infected brain.

    Science.gov (United States)

    Chang, Linda; Holt, John L; Yakupov, Renat; Jiang, Caroline S; Ernst, Thomas

    2013-04-01

    More HIV-infected individuals are living longer; however, how their brain function is affected by aging is not well understood. One hundred twenty-two men (56 seronegative control [SN] subjects, 37 HIV subjects with normal cognition [HIV+NC], 29 with HIV-associated neurocognitive disorder [HAND]) performed neuropsychological tests and had acceptable functional magnetic resonance imaging scans at 3 Tesla during tasks with increasing attentional load. With older age, SN and HIV+NC subjects showed increased activation in the left posterior (reserve, "bottom-up") attention network for low attentional-load tasks, and further increased activation in the left posterior and anterior ("top-down") attention network on intermediate (HIV+NC only) and high attentional-load tasks. HAND subjects had only age-dependent decreases in activation. Age-dependent changes in brain activation differed between the 3 groups, primarily in the left frontal regions (despite similar brain atrophy). HIV and aging act synergistically or interactively to exacerbate brain activation abnormalities in different brain regions, suggestive of a neuroadaptive mechanism in the attention network to compensate for declined neural efficiency. While the SN and HIV+NC subjects compensated for their declining attention with age by using reserve and "top-down" attentional networks, older HAND subjects were unable to compensate which resulted in cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample

    International Nuclear Information System (INIS)

    Tomse, Petra; Jensterle, Luka; Grmek, Marko; Zaletel, Katja; Pirtosek, Zvezdan; Trost, Maja; Dhawan, Vijay; Peng, Shichun; Eidelberg, David; Ma, Yilong

    2017-01-01

    The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p < 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p < 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression. (orig.)

  4. Imaging diagnosis in the elderly. Physiological and pathological changes in the aging brain

    International Nuclear Information System (INIS)

    Tokumaru, Aya M.; Saito, Yuko; Murayama, Shigeo

    2007-01-01

    The unprecedented aging of society is occurring rapidly Rather than a problem facing the future, this trend is already a reality in Japan. The discussion regarding the maintenance of the social environment surrounding medical care is important. Also important are the appropriate medical interventions for the diagnosis of various changes and conditions that are characteristic of the aging patient. However, it is extremely difficult to establish the border of morbid change if the brain-related change is normal. The main risk factor for the patient with dementia is aging itself. The neuroradiologist is an important source of precise imaging information as to what is normal and what is abnormal. (author)

  5. Personality traits and abnormal glucose regulation in middle-aged Swedish men and women.

    Science.gov (United States)

    Eriksson, Anna-Karin; Gustavsson, J Petter; Hilding, Agneta; Granath, Fredrik; Ekbom, Anders; Ostenson, Claes-Göran

    2012-01-01

    To examine associations between personality and abnormal glucose regulation. This cross-sectional study comprised 2152 men and 3143 women (43-66 years). Oral glucose tolerance test identified 316 men and 213 women with previously unknown impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, or type 2 diabetes. Personality traits antagonism (low agreeableness), impulsivity (low conscientiousness), hedonic capacity (high extraversion), negative affectivity (high neuroticism) and alexithymia (low openness) were measured by a self-report inventory. Based on distribution of scores, responses were divided into "low" (1 SD). Middle groups were considered reference groups. Prevalence odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. In men, OR for low antagonism was 0.3 (CI 0.2-0.6) (age- and multi-adjusted models) while in women, neither high nor low antagonism was associated to abnormal glucose regulation. Men and women with high hedonic capacity had ORs 0.5 (0.3-0.9) and 0.6 (0.4-1.0), respectively (age- and multi-adjusted models). The other scales illustrated no significant associations. No elevated risk of abnormal glucose regulation was observed for deviating scores on personality scales. Instead, reduced risks were indicated in men with low antagonism, and in men and women with high hedonic capacity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Dysplasia and overgrowth. Magnetic resonance imaging of pediatric brain abnormalities secondary to alterations in the mechanistic target of rapamycin pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shrot, Shai [Johns Hopkins University School of Medicine, Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Hwang, Misun; Huisman, Thierry A.G.M.; Soares, Bruno P. [Johns Hopkins University School of Medicine, Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Stafstrom, Carl E. [Johns Hopkins University School of Medicine, Division of Pediatric Neurology, Department of Neurology, Baltimore, MD (United States)

    2018-02-15

    The current classification of malformations of cortical development is based on the type of disrupted embryological process (cell proliferation, migration, or cortical organization/post-migrational development) and the resulting morphological anomalous pattern of findings. An ideal classification would include knowledge of biological pathways. It has recently been demonstrated that alterations affecting the mechanistic target of rapamycin (mTOR) signaling pathway result in diverse abnormalities such as dysplastic megalencephaly, hemimegalencephaly, ganglioglioma, dysplastic cerebellar gangliocytoma, focal cortical dysplasia type IIb, and brain lesions associated with tuberous sclerosis. We review the neuroimaging findings in brain abnormalities related to alterations in the mTOR pathway, following the emerging trend from morphology towards genetics in the classification of malformations of cortical development. This approach improves the understanding of anomalous brain development and allows precise diagnosis and potentially targeted therapies that may regulate mTOR pathway function. (orig.)

  7. Dysplasia and overgrowth. Magnetic resonance imaging of pediatric brain abnormalities secondary to alterations in the mechanistic target of rapamycin pathway

    International Nuclear Information System (INIS)

    Shrot, Shai; Hwang, Misun; Huisman, Thierry A.G.M.; Soares, Bruno P.; Stafstrom, Carl E.

    2018-01-01

    The current classification of malformations of cortical development is based on the type of disrupted embryological process (cell proliferation, migration, or cortical organization/post-migrational development) and the resulting morphological anomalous pattern of findings. An ideal classification would include knowledge of biological pathways. It has recently been demonstrated that alterations affecting the mechanistic target of rapamycin (mTOR) signaling pathway result in diverse abnormalities such as dysplastic megalencephaly, hemimegalencephaly, ganglioglioma, dysplastic cerebellar gangliocytoma, focal cortical dysplasia type IIb, and brain lesions associated with tuberous sclerosis. We review the neuroimaging findings in brain abnormalities related to alterations in the mTOR pathway, following the emerging trend from morphology towards genetics in the classification of malformations of cortical development. This approach improves the understanding of anomalous brain development and allows precise diagnosis and potentially targeted therapies that may regulate mTOR pathway function. (orig.)

  8. Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson's Disease.

    Science.gov (United States)

    Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2016-01-01

    The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson's disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD.

  9. Disrupted nodal and hub organization account for brain network abnormalities in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Yuko Koshimori

    2016-11-01

    Full Text Available The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease. This study aimed to investigate functional changes in sensorimotor and cognitive networks in parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the healthy control and patient groups. We found nodal and hub changes in patients compared with healthy controls, including the right pre-supplementary motor area, left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex, and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e. right pre-supplementary motor area and right mid-insula displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral dorsolateral prefrontal cortex possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of Parkinson’s disease.

  10. Pattern of mri brain abnormalities in rheumatic patients with neurological involvement: a tertiary care teaching hospital experience

    International Nuclear Information System (INIS)

    Parvez, K.; Arfaj, A.; Naseeb, F.; Daif, A.K.

    2015-01-01

    Objective: To explore the pattern of abnormalities seen on MRI in rheumatic patients with neurological manifestations and to interpret the findings in relation to clinical picture. Study Design: Descriptive study. Place and Duration of Study: Rheumatology unit, King Khalid University Hospital, Riyadh, Saudi Arabia from January 2013 to February 2014. Patients and Methods: We prospectively included rheumatic patients with neurological symptoms and signs. The clinical data were correlated with MRI findings by a team comprising of a rheumatologist, neurologist and neuro-radiologist. Data was analyzed using simple statistical analysis. Results: Fifty patients were recruited with a mean age of 36.4 ± 10.76 years (range 17-62). Among SLE patients with seizures, focal deficit and headache white matter hyperintensities were found in 9 (64.28%), 4 (50%), 4 (80%) patients respectively. Out of seven SLE patients with global dysfunction, 3 (42.85%) had brain atrophy and 2 (28.57%) normal MRI. In Behcet disease with focal deficit, 3 (75%) patients had white matter hyperintensities and 1 (25%) had brainstem involvement. In Behcet disease with headache, 2 (50%) had normal MRI, 1 (25%) brainstem hyper-intensities and 1 (25%) had subacute infarct. Two (66%) of three Primary APS patients had white matter hyperintensities while third (33%) had old infarct. Both patients of polyarteritisnodosa, had white matter hyperintensities. Out of two Wegener granulomatosis one had white matter hyperintensities and other had ischemic changes in optic nerves. The only one scleroderma patient had white matter hyperintensities. Conclusion: We found that white matter hyperintensities was the most common MRI abnormality in our study group which in most of the cases had poor clinical correlation. No distinct pattern of CNS involvement on MRI was observed in various rheumatic disorders. (author)

  11. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

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

    2016-03-01

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

  12. Abnormal error monitoring in math-anxious individuals: evidence from error-related brain potentials.

    Directory of Open Access Journals (Sweden)

    Macarena Suárez-Pellicioni

    Full Text Available This study used event-related brain potentials to investigate whether math anxiety is related to abnormal error monitoring processing. Seventeen high math-anxious (HMA and seventeen low math-anxious (LMA individuals were presented with a numerical and a classical Stroop task. Groups did not differ in terms of trait or state anxiety. We found enhanced error-related negativity (ERN in the HMA group when subjects committed an error on the numerical Stroop task, but not on the classical Stroop task. Groups did not differ in terms of the correct-related negativity component (CRN, the error positivity component (Pe, classical behavioral measures or post-error measures. The amplitude of the ERN was negatively related to participants' math anxiety scores, showing a more negative amplitude as the score increased. Moreover, using standardized low resolution electromagnetic tomography (sLORETA we found greater activation of the insula in errors on a numerical task as compared to errors in a non-numerical task only for the HMA group. The results were interpreted according to the motivational significance theory of the ERN.

  13. Brain abnormalities among the mentally retarded prenatally exposed atomic bomb survivors

    International Nuclear Information System (INIS)

    Schull, W.J.; Otake, Masanori; Nishitani, Hiromu; Hasuo, Kanehiro; Kobayashi, Takuro; Goto, Ikuo.

    1992-07-01

    An increased occurrence of severe mental retardation, with or without accompanying small head size, at specific gestational ages has been the most conspicuous effect on brain development of prenatal exposure to the bombings of Hiroshima and Nagasaki. A variety of biological mechanisms could be responsible for this finding, including cell killing and mismanaged neuronal migration. We describe here the findings on magnetic resonance imaging of the brains of five of these mentally retarded individuals, all of whom were exposed in the 8th through the 15th weeks following fertilization, the gestational period shown to be the most vulnerable to radiation-related damage. In the two cases exposed at the 8th or 9th week following fertilization, large areas of ectopic gray matter are seen, strong evidence of a failure of the neurons to migrate to their proper functional sites. The two individuals exposed in the 12th or 13th week show no readily recognized ectopic gray areas but do show mild macrogyria, which implies some impairment in the development of the cortical zone. Moreover, both have mega cisterna magna. Finally, the one individual seen who was exposed still later in development, in the 15th week, shows none of the changes seen in the other four individuals. This person's brain, though small, appears to have normal architecture. These findings are discussed in terms of the embryological events transpiring at the time of the prenatal exposure of these individuals to ionizing radiation. (author)

  14. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

    Directory of Open Access Journals (Sweden)

    Olga Kapellou

    2006-08-01

    Full Text Available We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33, which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001 independent of intrauterine or postnatal somatic growth.Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

  15. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder

    NARCIS (Netherlands)

    Noordermeer, Siri D. S.; Luman, Marjolein; Greven, Corina U.; Veroude, Kim; Faraone, Stephen V.; Hartman, Catharina A.; Hoekstra, Pieter J.; Franke, Barbara; Buitelaar, Jan K.; Heslenfeld, Dirk J.; Oosterlaan, Jaap

    2017-01-01

    BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of

  16. High prevalence of abnormalities on CT and MR imaging in children with unilateral sensorineural hearing loss irrespective of age or degree of hearing loss.

    Science.gov (United States)

    van Beeck Calkoen, E A; Sanchez Aliaga, E; Merkus, P; Smit, C F; van de Kamp, J M; Mulder, M F; Goverts, S T; Hensen, E F

    2017-06-01

    Evaluation of causal abnormalities identified on CT and MR imaging in children with unilateral sensorineural hearing loss (USNHL), and the association with age and severity of hearing loss. Retrospective cohort study. Tertiary referral otology/audiology center. 102 children diagnosed with USNHL between 2006 and 2016 were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss. Radiologic abnormalities of the inner ear and brain associated with USNHL. Using CT and/or MR imaging, causal abnormalities were identified in 49%, which is higher than previously reported (25-40%). The most frequently affected site was the labyrinth (29%), followed by the cochlear nerve (9%) and brain (7%). No significant difference in the number or type of abnormalities was found for the degree of hearing loss or age categories. Imaging is essential in the etiologic analysis of USNHL because of the high prevalence of causative abnormalities that can be identified with radiology, irrespective of the patients' age or degree of hearing loss. CT and MR imaging are complementary imaging options. The ideal imaging algorithm is controversial. Based on our findings, we conclude that there is limited additional diagnostic value of simultaneous dual modality imaging over sequential diagnostics. We therefore perform a stepwise radiological workup in order to maximize the diagnostic yield while minimizing impact and costs. If the primary imaging modality does not identify a cause for USNHL, performing the alternative imaging modality should be considered. Retrospective cohort study 2b. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Disrupted Gamma Synchrony after Mild Traumatic Brain Injury and Its Correlation with White Matter Abnormality

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    Chao Wang

    2017-10-01

    Full Text Available Mild traumatic brain injury (mTBI has been firmly associated with disrupted white matter integrity due to induced white matter damage and degeneration. However, comparatively less is known about the changes of the intrinsic functional connectivity mediated via neural synchronization in the brain after mTBI. Moreover, despite the presumed link between structural and functional connectivity, no existing studies in mTBI have demonstrated clear association between the structural abnormality of white matter axons and the disruption of neural synchronization. To investigate these questions, we recorded resting state EEG and diffusion tensor imaging (DTI from a cohort of military service members. A newly developed synchronization measure, the weighted phase lag index was applied on the EEG data for estimating neural synchronization. Fractional anisotropy was computed from the DTI data for estimating white matter integrity. Fifteen service members with a history of mTBI within the past 3 years were compared to 22 demographically similar controls who reported no history of head injury. We observed that synchronization at low-gamma frequency band (25–40 Hz across scalp regions was significantly decreased in mTBI cases compared with controls. The synchronization in theta (4–7 Hz, alpha (8–13 Hz, and beta (15–23 Hz frequency bands were not significantly different between the two groups. In addition, we found that across mTBI cases, the disrupted synchronization at low-gamma frequency was significantly correlated with the white matter integrity of the inferior cerebellar peduncle, which was also significantly reduced in the mTBI group. These findings demonstrate an initial correlation between the impairment of white matter integrity and alterations in EEG synchronization in the brain after mTBI. The results also suggest that disruption of intrinsic neural synchronization at low-gamma frequency may be a characteristic functional pathology

  18. [The blood-brain barrier in ageing persons].

    Science.gov (United States)

    Haaning, Nina; Damsgaard, Else Marie; Moos, Torben

    2018-03-26

    Brain capillary endothelial cells (BECs) form the ultra-tight blood-brain barrier (BBB). The permeability of the BBB increases with increasing age and neurovascular and neurodegenerative diseases. Major defects of the BBB can be initiated by increased permeability to plasma proteins in small arteriosclerotic arteries and release of proteins from degenerating neurons into the brain extracellular space. These proteins deposit in perivascular spaces, and subsequently negatively influence the BECs leading to decreased expression of barrier proteins. Detection of BBB defects by the use of non-invasive techniques is relevant for clinical use in settings with advanced age and severe brain disorders.

  19. Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

    Science.gov (United States)

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

    2017-10-01

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

  20. Fixel-based analysis reveals alterations is brain microstructure and macrostructure of preterm-born infants at term equivalent age

    Directory of Open Access Journals (Sweden)

    Kerstin Pannek

    Full Text Available Preterm birth causes significant disruption in ongoing brain development, frequently resulting in adverse neurodevelopmental outcomes. Brain imaging using diffusion MRI may provide valuable insight into microstructural properties of the developing brain. The aim of this study was to establish whether the recently introduced fixel-based analysis method, with its associated measures of fibre density (FD, fibre bundle cross-section (FC, and fibre density and bundle cross-section (FDC, is suitable for the investigation of the preterm infant brain at term equivalent age. High-angular resolution diffusion weighted images (HARDI of 55 preterm-born infants and 20 term-born infants, scanned around term-equivalent age, were included in this study (3 T, 64 directions, b = 2000 s/mm2. Postmenstrual age at the time of MRI, and intracranial volume (FC and FDC only, were identified as confounding variables. Gestational age at birth was correlated with all fixel measures in the splenium of the corpus callosum. Compared to term-born infants, preterm infants showed reduced FD, FC, and FDC in a number of regions, including the corpus callosum, anterior commissure, cortico-spinal tract, optic radiations, and cingulum. Preterm infants with minimal macroscopic brain abnormality showed more extensive reductions than preterm infants without any macroscopic brain abnormality; however, little differences were observed between preterm infants with no and with minimal brain abnormality. FC showed significant reductions in preterm versus term infants outside regions identified with FD and FDC, highlighting the complementary role of these measures. Fixel-based analysis identified both microstructural and macrostructural abnormalities in preterm born infants, providing a more complete picture of early brain development than previous diffusion tensor imaging (DTI based approaches. Keywords: Fixel-based analysis, Diffusion, Prematurity, Neonate

  1. Preterm brain injury on term-equivalent age MRI in relation to perinatal factors and neurodevelopmental outcome at two years.

    Directory of Open Access Journals (Sweden)

    Margaretha J Brouwer

    Full Text Available First, to apply a recently extended scoring system for preterm brain injury at term-equivalent age (TEA-MRI in a regional extremely preterm cohort; second, to identify independent perinatal factors associated with this score; and third, to assess the prognostic value of this TEA-MRI score with respect to early neurodevelopmental outcome.239 extremely preterm infants (median gestational age [range] in weeks: 26.6 [24.3-27.9], admitted to the Wilhelmina Children's Hospital between 2006 and 2012 were included. Brain abnormalities in white matter, cortical and deep grey matter and cerebellum and brain growth were scored on T1- and T2-weighted TEA-MRI using the Kidokoro scoring system. Neurodevelopmental outcome was assessed at two years corrected age using the Bayley Scales of Infant and Toddler Development, third edition. The association between TEA-MRI and perinatal factors as well as neurodevelopmental outcome was evaluated using multivariable regression analysis.The distribution of brain abnormalities and brain metrics in the Utrecht cohort differed from the original St. Louis cohort (p 7 days (β [95% confidence interval, CI]: 1.3 [.5; 2.0] and parenteral nutrition >21 days (2.2 [1.2; 3.2] were independently associated with higher global brain abnormality scores (p < .001. Global brain abnormality scores were inversely associated with cognitive (β in composite scores [95% CI]: -.7 [-1.2; -.2], p = .004, fine motor (β in scaled scores [95% CI]: -.1 [-.3; -.0], p = .007 and gross motor outcome (β in scaled scores [95% CI]: -.2 [-.3; -.1], p < .001 at two years corrected age, although the explained variances were low (R2 ≤.219.Patterns of brain injury differed between cohorts. Prolonged mechanical ventilation and parenteral nutrition were identified as independent perinatal risk factors. The prognostic value of the TEA-MRI score was rather limited in this well-performing cohort.

  2. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently health non-encephalopathic patients with cirrhosis; A controlled Study

    Energy Technology Data Exchange (ETDEWEB)

    Moore, J.W.; De Lacey, G.; Dunk, A.A.; Sinclair, T.S.; Mowat, M.A.G.; Brunt, P.W. (Royal Infirmary, Aberdeen (United Kingdom)); Deans, H. (Aberdeen Univ. (UK). Dept. of Medical Physics (United Kingdom)); Crawford, J.R. (Aberdeen University Medical School (United Kingdom). Department of Psychology (United Kingdom)); Besson, J.A.O. (Aberdeen University Medical School (United Kingdom). Department of Mental Health (United Kingdom))

    1989-11-01

    By means of psychometric testing, we have determined the frequency of latent hepatic encephalopathy in a group of 19 cirrhotics with no clinical evidence of encephalopathy. Magnetic resonance imaging (MRI) of the brain was performed in order to determine whether morphological cerebral abnormalities were associated with latent encephalopathy. Nineteen age and educationally matched patient with normal liver function acted as controls. Significant differences (P < 0.05) between cirrhotics and controls were found in tests of short-term visual memory and speed of reaction to light (cirrhotics 326 ( 132 ms vs. controls 225 ) 36 ms), sound (cirrhotics 361 ( 152 ms vs. controls 236 ) 52 ms) and choice (cirrhotics 651 ( 190 ms vs. controls 406 ) 101 ms) stimuli (all values mean S.D.). Reitan trail test performance, however, was similar in both groups. ( Trail A: cirrhotics 43 ( 19 s vs. controls 35 ) 13 s; Trail B: cirrhotics 105 ( 66 s vs. controls 93 ) 36 s.) In patients with cirrhosis, MRI revealed statistically significant increases in the maximum fissure width of right frontal sulci, light and left parietal sulci, inter-hemispheric fissure width and in bicaudafe index. These changes, indicating cerebral atrophy, were largely confined to alcoholics. There was poor correlation between measurements of cerebral morphology and neuropsychological performance, only 10% of associations achieving statistical significance. (author). 2 refs.; 3 figs.; 5 tabs.

  4. Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently health non-encephalopathic patients with cirrhosis

    International Nuclear Information System (INIS)

    Moore, J.W.; De Lacey, G.; Dunk, A.A.; Sinclair, T.S.; Mowat, M.A.G.; Brunt, P.W.; Deans, H.; Crawford, J.R.; Besson, J.A.O.

    1989-01-01

    By means of psychometric testing, we have determined the frequency of latent hepatic encephalopathy in a group of 19 cirrhotics with no clinical evidence of encephalopathy. Magnetic resonance imaging (MRI) of the brain was performed in order to determine whether morphological cerebral abnormalities were associated with latent encephalopathy. Nineteen age and educationally matched patient with normal liver function acted as controls. Significant differences (P < 0.05) between cirrhotics and controls were found in tests of short-term visual memory and speed of reaction to light (cirrhotics 326 ] 132 ms vs. controls 225 ] 36 ms), sound (cirrhotics 361 ] 152 ms vs. controls 236 ] 52 ms) and choice (cirrhotics 651 ] 190 ms vs. controls 406 ] 101 ms) stimuli (all values mean ] S.D.). Reitan trail test performance, however, was similar in both groups. ( Trail A: cirrhotics 43 ] 19 s vs. controls 35 ] 13 s; Trail B: cirrhotics 105 ] 66 s vs. controls 93 ] 36 s.) In patients with cirrhosis, MRI revealed statistically significant increases in the maximum fissure width of right frontal sulci, light and left parietal sulci, inter-hemispheric fissure width and in bicaudafe index. These changes, indicating cerebral atrophy, were largely confined to alcoholics. There was poor correlation between measurements of cerebral morphology and neuropsychological performance, only 10% of associations achieving statistical significance. (author). 2 refs.; 3 figs.; 5 tabs

  5. Adaptation of brain functional and structural networks in aging.

    Directory of Open Access Journals (Sweden)

    Annie Lee

    Full Text Available The human brain, especially the prefrontal cortex (PFC, is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI, and high angular resolution diffusion imaging (HARDI, and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  6. Adaptation of brain functional and structural networks in aging.

    Science.gov (United States)

    Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2015-01-01

    The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  7. A longitudinal study of brain volume changes in normal aging

    Energy Technology Data Exchange (ETDEWEB)

    Takao, Hidemasa, E-mail: takaoh-tky@umin.ac.jp [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Hayashi, Naoto [Department of Computational Diagnostic Radiology and Preventive Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Ohtomo, Kuni [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)

    2012-10-15

    Purpose: To evaluate the effect of normal aging on brain volumes and examine the effects of age and sex on the rates of changes in global and regional brain volumes. Methods: A total of 199 normal subjects (65 females and 134 males, mean age = 56.4 ± 9.9 years, age range = 38.1–82.9 years) were included in this study. Each subject was scanned twice, at an interval of about 2 years (range = 1.5–2.3 years). Two-time-point percentage brain volume change (PBVC) was estimated with SIENA 2.6. Results: The mean annualized PBVC was −0.23%/y. Analysis of covariance (ANCOVA) for annual brain volume changes revealed a main effect of age. There was no main effect of sex, nor was there a sex-by-age interaction. Voxel-wise analysis revealed a negative correlation between age and edge displacement values mainly in the periventricular region. Conclusions: The results of our study indicate that brain atrophy accelerates with increasing age and that there is no gender difference in the rate of brain atrophy.

  8. A longitudinal study of brain volume changes in normal aging

    International Nuclear Information System (INIS)

    Takao, Hidemasa; Hayashi, Naoto; Ohtomo, Kuni

    2012-01-01

    Purpose: To evaluate the effect of normal aging on brain volumes and examine the effects of age and sex on the rates of changes in global and regional brain volumes. Methods: A total of 199 normal subjects (65 females and 134 males, mean age = 56.4 ± 9.9 years, age range = 38.1–82.9 years) were included in this study. Each subject was scanned twice, at an interval of about 2 years (range = 1.5–2.3 years). Two-time-point percentage brain volume change (PBVC) was estimated with SIENA 2.6. Results: The mean annualized PBVC was −0.23%/y. Analysis of covariance (ANCOVA) for annual brain volume changes revealed a main effect of age. There was no main effect of sex, nor was there a sex-by-age interaction. Voxel-wise analysis revealed a negative correlation between age and edge displacement values mainly in the periventricular region. Conclusions: The results of our study indicate that brain atrophy accelerates with increasing age and that there is no gender difference in the rate of brain atrophy

  9. Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

    Science.gov (United States)

    Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

    2017-07-01

    Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

  10. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

    2017-01-01

    The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

  11. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  12. Accelerated brain aging in schizophrenia : A longitudinal pattern recognition study

    NARCIS (Netherlands)

    Schnack, Hugo G.; Van Haren, Neeltje E M; Nieuwenhuis, Mireille; Pol, Hilleke E Hulshoff; Cahn, Wiepke; Kahn, René S.

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  13. Accelerated Brain Aging in Schizophrenia : A Longitudinal Pattern Recognition Study

    NARCIS (Netherlands)

    Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  14. Corpus callosum vasculature predicts white matter microstructure abnormalities following pediatric mild traumatic brain injury.

    Science.gov (United States)

    Wendel, Kara M; Lee, Jeong Bin; Affeldt, Bethann; Hamer, Mary; Harahap-Carrillo, Indira S; Pardo, Andrea C; Obenaus, Andre

    2018-05-09

    Emerging data suggest that pediatric traumatic brain injury (TBI) is associated with impaired developmental plasticity and poorer neuropsychological outcomes than adults with similar head injuries. Unlike adult mild TBI (mTBI), the effects of mTBI on white matter (WM) microstructure and vascular supply are not well-understood in the pediatric population. The cerebral vasculature plays an important role providing necessary nutrients and removing waste. To address this critical element, we examined the microstructure of the corpus callosum (CC) following pediatric mTBI using diffusion tensor imaging (DTI), and investigated myelin, oligodendrocytes, and vasculature of WM with immunohistochemistry. We hypothesized that pediatric mTBI leads to abnormal WM microstructure and impacts the vasculature within the CC, and that these alterations to WM vasculature contribute to the long-term altered microstructure. We induced a closed head injury mTBI at postnatal day 14, then at 4, 14, and 60 days post injury (DPI) mice were sacrificed for analysis. We observed persistent changes in apparent diffusion coefficient (ADC) within the ipsilateral CC following mTBI, indicating microstructural changes, but surprisingly changes in myelin and oligodendrocyte densities were minimal. However, vasculature features of the ipsilateral CC such as vessel density, length, and number of junctions were persistently altered following mTBI. Correlative analysis showed a strong inverse relationship between ADC and vessel density at 60 DPI, suggesting increased vessel density following mTBI may restrict WM diffusion characteristics. Our findings suggest that WM vasculature contributes to the long-term microstructural changes within the ipsilateral CC following mTBI.

  15. Magnetic resonance imaging of the brain in normal aging and dementia

    International Nuclear Information System (INIS)

    Alavi, A.; Fazekas, F.; Chawluk, J.; Zimmerman, R.

    1987-01-01

    The unusual sensitivity of magnetic resonance imaging in detecting white matter lesions has yielded striking results in studying the aging brain and in diagnosing a variety of central nervous system disorders. These lesions are most obvious in the periventricular white matter and appear as punctate or confluent hyperintense abnormalities on T2-weighted images. Their correlation with increasing age and the ensuing increase of cardiovascular risk factors suggests ischemic damage as their probable underlying pathologic cause. MRI thus may prove an early and very sensitive indicator of incipient cerebrovascular disease, adding information on the association of vascular damage with the development of dementing illness. This report is a preliminary communication of an ongoing study which is evaluating the importance of these findings in the 'normal' aging brain and different forms of dementia. 11 refs.; 1 table

  16. Brain arterial aging and its relationship to Alzheimer dementia.

    Science.gov (United States)

    Gutierrez, Jose; Honig, Lawrence; Elkind, Mitchell S V; Mohr, Jay P; Goldman, James; Dwork, Andrew J; Morgello, Susan; Marshall, Randolph S

    2016-04-19

    To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. © 2016 American Academy of Neurology.

  17. Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery

    International Nuclear Information System (INIS)

    Hughes, David G.; Jackson, Alan; Mason, Damon L.; Berry, Elizabeth; Hollis, Sally; Yates, David W.

    2004-01-01

    Mild traumatic brain injury (MTBI) is a common reason for hospital attendance and is associated with significant delayed morbidity. We studied a series of 80 persons with MTBI. Magnetic resonance imaging (MRI) and neuropsychological testing were used in the acute phase and a questionnaire for post-concussion syndrome (PCS) and return to work status at 6 months. In 26 subjects abnormalities were seen on MRI, of which 5 were definitely traumatic. There was weak correlation with abnormal neuropsychological tests for attention in the acute period. There was no significant correlation with a questionnaire for PCS and return to work status. Although non-specific abnormalities are frequently seen, standard MRI techniques are not helpful in identifying patients with MTBI who are likely to have delayed recovery. (orig.)

  18. Abnormal brain function in neuromyelitis optica: A fMRI investigation of mPASAT.

    Science.gov (United States)

    Wang, Fei; Liu, Yaou; Li, Jianjun; Sondag, Matthew; Law, Meng; Zee, Chi-Shing; Dong, Huiqing; Li, Kuncheng

    2017-10-01

    Cognitive impairment with the Neuromyelitis Optica (NMO) patients is debated. The present study is to study patterns of brain activation in NMO patients during a pair of task-related fMRI. We studied 20 patients with NMO and 20 control subjects matched for age, gender, education and handedness. All patients with NMO met the 2006 Wingerchuk diagnostic criteria. The fMRI paradigm included an auditory attention monitoring task and a modified version of the Paced Auditory Serial Addition Task (mPASAT). Both tasks were temporally and spatially balanced, with the exception of task difficulty. In mPASAT, Activation regions in control subjects included bilateral superior temporal gyri (BA22), left inferior frontal gyrus (BA45), bilateral inferior parietal lobule (BA7), left cingulate gyrus (BA32), left insula (BA13), and cerebellum. Activation regions in NMO patients included bilateral superior temporal gyri (BA22), left inferior frontal gyrus (BA9), right cingulate gyrus (BA32), right inferior parietal gyrus (BA40), left insula (BA13) and cerebellum. Some dispersed cognition related regions are greater in the patients. The present study showed altered cerebral activation during mPASAT in patients with NMO relative to healthy controls. These results are speculated to provide further evidence for brain plasticity in patients with NMO. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Brain aging and neurodegeneration: from a mitochondrial point of view.

    Science.gov (United States)

    Grimm, Amandine; Eckert, Anne

    2017-11-01

    Aging is defined as a progressive time-related accumulation of changes responsible for or at least involved in the increased susceptibility to disease and death. The brain seems to be particularly sensitive to the aging process since the appearance of neurodegenerative diseases, including Alzheimer's disease, is exponential with the increasing age. Mitochondria were placed at the center of the 'free-radical theory of aging', because these paramount organelles are not only the main producers of energy in the cells, but also to main source of reactive oxygen species. Thus, in this review, we aim to look at brain aging processes from a mitochondrial point of view by asking: (i) What happens to brain mitochondrial bioenergetics and dynamics during aging? (ii) Why is the brain so sensitive to the age-related mitochondrial impairments? (iii) Is there a sex difference in the age-induced mitochondrial dysfunction? Understanding mitochondrial physiology in the context of brain aging may help identify therapeutic targets against neurodegeneration. This article is part of a series "Beyond Amyloid". © 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  20. Nutritional strategies to optimise cognitive function in the aging brain.

    Science.gov (United States)

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

    2016-11-01

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

  1. Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging: implications for functional defects in aged eggs

    Science.gov (United States)

    Mackenzie, Amelia C.L.; Kyle, Diane D.; McGinnis, Lauren A.; Lee, Hyo J.; Aldana, Nathalia; Robinson, Douglas N.; Evans, Janice P.

    2016-01-01

    STUDY HYPOTHESIS Cellular aging of the egg following ovulation, also known as post-ovulatory aging, is associated with aberrant cortical mechanics and actomyosin cytoskeleton functions. STUDY FINDING Post-ovulatory aging is associated with dysfunction of non-muscle myosin-II, and pharmacologically induced myosin-II dysfunction produces some of the same deficiencies observed in aged eggs. WHAT IS KNOWN ALREADY Reproductive success is reduced with delayed fertilization and when copulation or insemination occurs at increased times after ovulation. Post-ovulatory aged eggs have several abnormalities in the plasma membrane and cortex, including reduced egg membrane receptivity to sperm, aberrant sperm-induced cortical remodeling and formation of fertilization cones at the site of sperm entry, and reduced ability to establish a membrane block to prevent polyspermic fertilization. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Ovulated mouse eggs were collected at 21–22 h post-human chorionic gonadotrophin (hCG) (aged eggs) or at 13–14 h post-hCG (young eggs), or young eggs were treated with the myosin light chain kinase (MLCK) inhibitor ML-7, to test the hypothesis that disruption of myosin-II function could mimic some of the effects of post-ovulatory aging. Eggs were subjected to various analyses. Cytoskeletal proteins in eggs and parthenogenesis were assessed using fluorescence microscopy, with further analysis of cytoskeletal proteins in immunoblotting experiments. Cortical tension was measured through micropipette aspiration assays. Egg membrane receptivity to sperm was assessed in in vitro fertilization (IVF) assays. Membrane topography was examined by low-vacuum scanning electron microscopy (SEM). MAIN RESULTS AND THE ROLE OF CHANCE Aged eggs have decreased levels and abnormal localizations of phosphorylated myosin-II regulatory light chain (pMRLC; P = 0.0062). Cortical tension, which is mediated in part by myosin-II, is reduced in aged mouse eggs when compared with

  2. Relationship Between Advanced Maternal Age, Hiesho (Sensitivity to Cold) and Abnormal Delivery in Japan

    Science.gov (United States)

    Nakamura, Sachiyo; Horiuchi, Shigeko

    2013-01-01

    Background: In Japan, the proportion of women aged 35 and older giving birth has greatly increased in recent years, and maternal age is continuing to increase. Advanced maternal age is a risk factor for abnormal delivery, as is hiesho (sensitivity to cold). Research Question: This study aimed to assess whether advanced maternal age and hiesho precipitate premature delivery, premature rupture of membranes, weak labor pains, prolonged labor and atonic bleeding. Method: The study design was a descriptive comparative study with a retrospective cohort group design. Subjects in this study were 2,810 Japanese women in hospital after childbirth. The research methods employed were a paper questionnaire and extraction of data from medical records. Results: Comparing the rate of occurrence of abnormal delivery among women aged 35 to 39 according to whether or not they had hiesho, results were premature delivery OR: 3.51 (95% CI: 1.66-7.43), premature rupture of membranes OR: 1.25 (95% CI: 0.90-1.74), weak labor pains OR: 2.94 (95% CI: 1.65-5.24), prolonged labor OR: 2.56 (95% CI: 1.23-5.26), and atonic bleeding, OR: 1.65 (95% CI: 0.14-2.40) when hiesho was present. Among women aged 40 and over, results were premature delivery OR: 5.09 (95% CI: 1.16-22.20), premature rupture of membranes OR: 1.60 (95% CI: 0.73-3.46), weak labor pains OR: 7.02 (95% CI: 1.56-31.55), prolonged labor OR:7.19 (95% CI: 1.49-34.60) and atonic bleeding OR: 2.00 (95% CI: 0.64-6.23). Conclusions: Regardless of maternal age, the presence of hiesho is a risk factor that can precipitate premature delivery, premature rupture of membranes, weak labor pains, prolonged labor and atonic bleeding. Furthermore, hiesho coupled with advanced maternal age increases the incidence of premature delivery, weak labor pains and prolonged labor. PMID:24062862

  3. Insulin, Aging, and the Brain: Mechanisms and Implications

    OpenAIRE

    Akintola, Abimbola A.; van Heemst, Diana

    2015-01-01

    There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into t...

  4. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    Science.gov (United States)

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Omega-3 polyunsaturated fatty acids and brain aging.

    Science.gov (United States)

    Denis, Isabelle; Potier, Brigitte; Heberden, Christine; Vancassel, Sylvie

    2015-03-01

    The literature on the influence of dietary omega-3 polyunsaturated fatty acid (ω-3 PUFA) on brain aging has grown exponentially during the last decade. Many avenues have been explored but no global picture or clear evidence has emerged. Experimental studies have shown that ω-3 PUFA is involved in many neurobiological processes that are involved in neurotransmission and neuroprotection, indicating that these PUFAs may prevent age-related brain damage. Human studies have revealed only a weak link between ω-3 PUFA status and cognitive aging, whereas interventional studies have yet to confirm it. The purpose of this review is to analyze the developments in the area during the last 2 years. Human brain MRI studies have confirmed previous findings that ω-3 PUFA can protect the brain during aging; two intervention studies obtained clear evidence. We also analyzed the experimental data clarifying the involvement of ω-3 PUFA in neurotransmission, neuroprotection (including prevention of peroxidation, inflammation, and excitotoxicity), and neurogenesis, thereby helping the brain cope with aging. These recent human and experimental studies provide support for and clarification of how ω-3 PUFA protect against brain aging and highlight the main lines for future research.

  6. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  7. Abnormal functional integration across core brain networks in migraine without aura.

    Science.gov (United States)

    Yu, Dahua; Yuan, Kai; Luo, Lin; Zhai, Jinquan; Bi, Yanzhi; Xue, Ting; Ren, Xiaoying; Zhang, Ming; Ren, Guoyin; Lu, Xiaoqi

    2017-01-01

    As a complex subjective experience, pain processing may be related to functional integration among intrinsic connectivity networks of migraine patients without aura. However, few study focused on the pattern alterations in the intrinsic connectivity networks of migraine patients without aura. Thirty-one migraine patients without aura and 31 age- and education-matched healthy controls participated in this study. After identifying the default mode network, central executive network and salience network as core intrinsic connectivity networks by using independent component analysis, functional connectivity, and effective connectivity during the resting state were used to investigate the abnormalities in intrinsic connectivity network interactions. Migraine patients without aura showed decreased functional connectivity among intrinsic connectivity networks compared with healthy controls. The strength of causal influences from the right frontoinsular cortex to the right anterior cingulate cortex became weaker, and the right frontoinsular cortex to the right medial prefrontal cortex became stronger in migraine patients without aura. These changes suggested that the salience network may play a major role in the pathophysiological features of migraine patients without aura and helped us to synthesize previous findings into an aberrant network dynamical framework.

  8. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    Directory of Open Access Journals (Sweden)

    Marta Karolina Zamroziewicz

    2016-06-01

    Full Text Available Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition’s impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition – from entire diets to specific nutrients – affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns, along with (ii modern indices of brain health derived from high-resolution magnetic resonance imaging. By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  9. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    International Nuclear Information System (INIS)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M.; Poole, Ian; Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D.

    2012-01-01

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged ≥60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged ≥60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  10. Brain Natriuretic Peptide, Atrial Natriuretic Peptide and Endothelin-1 response to peak exercise in patients with coronary artery disease and correlation with myocardial perfusion scintigraphy abnormalities

    International Nuclear Information System (INIS)

    Erbas, B.; Ergun, E.; Koray, Z.; Kabakci, G.; Yildirir, A.; Kes, S.

    2002-01-01

    Aim: Plasma Brain Natriuretic Peptide (BNP) has been known as a promising marker of ventricular dysfunction in cardiac patients. There are conflicting reports about its response to exercise testing. Therefore, this study was performed to investigate the exercise induced changes in BNP, Atrial Natriuretic Peptide (ANP) and Endothelin-1 (E) levels and their correlation with perfusion abnormalities on myocardial perfusion scintigraphy (MPS). Materials and Methods: Study group consisted of 35 patients (mean age=53.9+11.8) who underwent MPS with suspicion or diagnosis of coronary artery disease. Plasma levels of BNP, ANP, and E were measured at rest and after symptom-limited ergometry. Patients were divided into two groups according to the presence of perfusion abnormality (i.e. ischemia or infarction) on MPS. Results: BNP, ANP and E levels did not change significantly with exercise, however baseline levels of BNP, ANP levels and peak-exercise level of BNP in patients with perfusion abnormalities were significantly higher. Hypertensive patients with or without perfusion abnormalities had higher baseline BNP, ANP levels, and peak-exercise BNP levels compared to normotensives. BNP levels at rest and after exercise had a significant correlation with age (r=0.57, p=0.04; r=0.58, p=0.04), as well as baseline ANP values (r=0.37, p=0.033). Highest baseline BNP, ANP and exercise BNP levels were observed in patients with infarction. Conclusion: Exercise-testing did not induce significant changes in plasma levels of BNP, ANP and E. Higher BNP levels had correlation with the presence of ischemia, infarction and hypertension, as well as, increasing age

  11. Problems in CT diagnosis of the aging brain

    International Nuclear Information System (INIS)

    Kohlmeyer, K.

    1989-01-01

    The different methods of measuring the intracranial CSF spaces on CT images are described. The values obtained are demonstrated to separate the normal aging brain from the brain in senile dementia of Alzheimer's type. The CT criteria for the diagnosis of multiinfarctdementia are shown. The significance of CT studies in senile depression is discussed. The problem of vascular encephalopathy (leukoaraiosis) in normal aging of the brain and in dementia is considered in particular, and even the occurrence of intracranial space-occupying lesions and normal pressure hydrocephalus, as treatable causes of dementia and depression, are mentioned. The data and results of my own CT research on normal brain aging, dementia and depression are presented with reference to the literature. (orig.) [de

  12. Emotion and Aging: Evidence from Brain and Behavior

    Directory of Open Access Journals (Sweden)

    Natalie eEbner

    2014-09-01

    Full Text Available Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the thirteen papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take.

  13. The genetic and environmental determinants of the association between brain abnormalities and schizophrenia: the schizophrenia twins and relatives consortium.

    Science.gov (United States)

    van Haren, Neeltje E M; Rijsdijk, Fruhling; Schnack, Hugo G; Picchioni, Marco M; Toulopoulou, Timothea; Weisbrod, Matthias; Sauer, Heinrich; van Erp, Theo G; Cannon, Tyrone D; Huttunen, Matti O; Boomsma, Dorret I; Hulshoff Pol, Hilleke E; Murray, Robin M; Kahn, Rene S

    2012-05-15

    Structural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium). An international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling. The heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (-.22 [-.30/-.14]) and white matter (-.17 [-.25/-.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively). Some of the genes that transmit the risk for Sz also influence cerebral (white matter) volume. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. MRI assessment of whole-brain structural changes in aging.

    Science.gov (United States)

    Guo, Hui; Siu, William; D'Arcy, Ryan Cn; Black, Sandra E; Grajauskas, Lukas A; Singh, Sonia; Zhang, Yunting; Rockwood, Kenneth; Song, Xiaowei

    2017-01-01

    One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r 2 >0.69; P age ( r 2 >0.29; P 26.48, P aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Influences of brain development and ageing on cortical interactive networks.

    Science.gov (United States)

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

    2011-02-01

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

  17. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    Science.gov (United States)

    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

  18. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Charles W. Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  20. Structural MRI markers of brain aging early after ischemic stroke.

    Science.gov (United States)

    Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

    2017-07-11

    To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  1. Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

    Science.gov (United States)

    Cole, James H

    2018-07-01

    The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

  2. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

  3. Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury.

    Science.gov (United States)

    Robinson, Shenandoah; Corbett, Christopher J; Winer, Jesse L; Chan, Lindsay A S; Maxwell, Jessie R; Anstine, Christopher V; Yellowhair, Tracylyn R; Andrews, Nicholas A; Yang, Yirong; Sillerud, Laurel O; Jantzie, Lauren L

    2018-04-01

    Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60min via laparotomy. Shams underwent anesthesia and laparotomy for 60min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25-35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities

  4. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality

    NARCIS (Netherlands)

    van Tol, Marie-José; Veer, Ilya M.; van der Wee, Nic J. A.; Aleman, André; van Buchem, Mark A.; Rombouts, Serge A. R. B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether

  5. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder : Abnormal salience circuitry and relations to positive emotionality

    NARCIS (Netherlands)

    van Tol, Marie-Jose; Veer, Ilya M.; van der Wee, Nic J. A.; Aleman, Andre; van Buchem, Mark A.; Rombouts, Serge A. R. B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether

  6. Steroid abnormalities and the developing brain: Declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia

    OpenAIRE

    Maheu, Françoise S.; Merke, Deborah P.; Schroth, Elizabeth A.; Keil, Margaret F.; Hardin, Julie; Poeth, Kaitlin; Pine, Daniel S.; Ernst, Monique

    2007-01-01

    Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effect of these hormones on the neural networks underlying memory. Using Congenital Adrenal Hyperplasia (CAH) as a naturalistic model of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12 to 14 years...

  7. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

    2006-06-15

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  8. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N.; MacManus, D.G.; Collinge, J.

    2006-01-01

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  9. Association between maternal vascular murmur and the small-for-gestational-age fetus with abnormal umbilical artery Doppler flow

    DEFF Research Database (Denmark)

    Riknagel, Diana; Farlie, Richard; Hedegaard, Morten

    2017-01-01

    OBJECTIVE: To investigate the association between maternal vascular murmurs (MVMs) and fetal growth restriction (defined as small-for-gestational-age [SGA] fetus) and abnormal Doppler pulsatility index (PI) of the uterine and/or umbilical arteries. METHODS: A cross-sectional study of women aged 1...

  10. Age-related functional brain changes in young children.

    Science.gov (United States)

    Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

    2017-07-15

    Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Revisiting nicotine's role in the ageing brain and cognitive impairment

    DEFF Research Database (Denmark)

    Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

    2017-01-01

    Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

  12. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ming-Xiong Huang

    2014-01-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz that can be measured and localized by resting-state magnetoencephalography (MEG. In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes, our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes, blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

  13. Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

    Science.gov (United States)

    Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

    2014-01-01

    Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

  14. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between...

  15. In vivo calcium imaging of the aging and diseased brain

    International Nuclear Information System (INIS)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga

    2008-01-01

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  16. The role of mitochondrial ROS in the aging brain.

    Science.gov (United States)

    Stefanatos, Rhoda; Sanz, Alberto

    2018-03-01

    The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mtROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mtROS are produced at the molecular level, how different brain cells and regions produce different amounts of mtROS, and how mtROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age-associated increases in mtROS are a cause or a consequence of aging. © 2017 Federation of European Biochemical Societies.

  17. The dopaminergic system in the aging brain of Drosophila

    Directory of Open Access Journals (Sweden)

    Katherine E White

    2010-12-01

    Full Text Available Drosophila models of Parkinson’s disease are characterised by two principal phenotypes: the specific loss of dopaminergic neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analysed the dopaminergic system and motor behavior in aging Drosophila. Dopaminergic neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH>mCD8::GFP and cell type-specific MARCM clones revealed that dopaminergic neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, dopaminergic neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH>Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct dopaminergic behaviors in Drosophila. Moreover, dopaminergic neurons were maintained between early- and late life, as quantified by TH>mCD8::GFP and anti-TH labelling, indicating that adult onset, age-related degeneration of dopaminergic neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson’s disease as well as other disorders affecting dopaminergic neurons

  18. Sex differences in normal age trajectories of functional brain networks.

    Science.gov (United States)

    Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

    2015-04-01

    Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

  19. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yan, E-mail: clare1475@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Qin Lingdi, E-mail: flyfool318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Chen Jun, E-mail: doctor_cj@msn.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Qian Lijun, E-mail: dearqlj@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Tao Jing, E-mail: jing318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Fang Yiru, E-mail: fangyr@sina.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Xu Jianrong, E-mail: xujianr@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China)

    2011-11-15

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p < 0.001 [FDR corrected], t > 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  20. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

    International Nuclear Information System (INIS)

    Zhou Yan; Qin Lingdi; Chen Jun; Qian Lijun; Tao Jing; Fang Yiru; Xu Jianrong

    2011-01-01

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  1. Role of 99mTc-ECD brain SPECT in the detection of cerebral perfusion abnormality in cases of Attention Deficit Hyperactivity Disorder

    International Nuclear Information System (INIS)

    Kumar, A.; Phom, H.; Thomas, E.J.; Tripathi, M.; Chandrashekar, N.; Bal, C.S.; Zamir, H.; Gulati, S.; Kalra, V.

    2002-01-01

    Aim: A randomized placebo controlled drug trial with Mentat, a herbal pharmacological agent, was initiated in January 2000 in the department of pediatrics at AIIMS, New Delhi, to compare the efficacy of Mentat with a placebo in school children with Attention Deficit Hyperactivity Disorder (ADHD). Materials and Methods: Contact was established with 12 Public schools in Delhi, to identify poor performers in classes I-V (age 6-12 yrs.). About 195 children with poor school performance were recruited in the study. They were screened for causes of poor performance, which included attention problems, hyperactivity, behavior problems, emotional problems, mental sub-normality and learning disability. ADHD suspected children were identified using the Malin's WISC, Connor's rating scale, Problem Behavior checklist, Bender Gestalt test and some sub tests of the Kaufman's Assessment Battery for Children (K-ABC). Sixty children diagnosed as ADHD (using DSM-IV criteria), with an IQ between 90-110, were enrolled into the study. Of the 60 children randomized in the study, 30 received Mentat and 30 received an identical looking placebo. The drug/Placebo was given for a six-month period. 99mTC-ECD brain SPECT was performed in a subset of 34 children with ADHD. Results: Abnormal cerebral perfusion was seen in 23/34; thalamic hypoperfusion in 11, basal ganglia hypoperfusion in 9, thalamus and basal ganglia hypoperfusion in 2 and basifrontal hypoperfusion in 1. So far, in ten children with abnormal pretreatment scans, post treatment scans have also been done. In mentat group, 2/5 children showed normalization of perfusion abnormality after treatment whereas in placebo group, 1/5. Conclusion: This study suggests that there is selective focal cerebral hypoperfusion in cases of ADHD and 99mTc-ECD brain SPECT can be used for evaluation and further monitoring of therapeutic outcome in such cases

  2. Aging exacerbates intracerebral hemorrhage-induced brain injury.

    Science.gov (United States)

    Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

    2009-09-01

    Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

  3. Clinical manifestations that predict abnormal brain computed tomography (CT in children with minor head injury

    Directory of Open Access Journals (Sweden)

    Nesrin Alharthy

    2015-01-01

    Full Text Available Background: Computed tomography (CT used in pediatric pediatrics brain injury (TBI to ascertain neurological manifestations. Nevertheless, this practice is associated with adverse effects. Reports in the literature suggest incidents of morbidity and mortality in children due to exposure to radiation. Hence, it is found imperative to search for a reliable alternative. Objectives: The aim of this study is to find a reliable clinical alternative to detect an intracranial injury without resorting to the CT. Materials and Methods: Retrospective cross-sectional study was undertaken in patients (1-14 years with blunt head injury and having a Glasgow Coma Scale (GCS of 13-15 who had CT performed on them. Using statistical analysis, the correlation between clinical examination and positive CT manifestation is analyzed for different age-groups and various mechanisms of injury. Results: No statistically significant association between parameteres such as Loss of Consciousness, ′fall′ as mechanism of injury, motor vehicle accidents (MVA, more than two discrete episodes of vomiting and the CT finding of intracranial injury could be noted. Analyzed data have led to believe that GCS of 13 at presentation is the only important clinical predictor of intracranial injury. Conclusion: Retrospective data, small sample size and limited number of factors for assessing clinical manifestation might present constraints on the predictive rule that was derived from this review. Such limitations notwithstanding, the decision to determine which patients should undergo neuroimaging is encouraged to be based on clinical judgments. Further analysis with higher sample sizes may be required to authenticate and validate findings.

  4. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Science.gov (United States)

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  5. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Directory of Open Access Journals (Sweden)

    Julie Nemecek

    Full Text Available Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA to amplify abnormal prion protein (PrP(TSE from highly diluted variant Creutzfeldt-Jakob disease (vCJD-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE in tissues and blood. Macaque vCJD PrP(TSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA. Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV, a close relative of the bank vole, seeded with macaque vCJD PrP(TSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N. We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE. Meadow vole brain (170N/N PrP genotype was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE was more permissive than human PrP(TSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE from brains of humans and macaques with vCJD. PrP(TSE signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

  6. Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

    Science.gov (United States)

    Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Farfel, José Marcelo; Leite, Renata; Pasqualucci, Carlos Augusto; Rosemberg, Sérgio; Nitrini, Ricardo; Saldiva, Paulo Hilário Nascimento; Filho, Wilson Jacob

    2007-01-01

    Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

  7. Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

    Science.gov (United States)

    Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang

    2018-01-01

    Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    Science.gov (United States)

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  9. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Science.gov (United States)

    Krauer, Fabienne; Riesen, Maurane; Reveiz, Ludovic; Oladapo, Olufemi T; Martínez-Vega, Ruth; Porgo, Teegwendé V; Haefliger, Anina; Broutet, Nathalie J; Low, Nicola

    2017-01-01

    The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal

  10. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Directory of Open Access Journals (Sweden)

    Fabienne Krauer

    2017-01-01

    Full Text Available The World Health Organization (WHO stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality.The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693. We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity, we found that more than half the relevant studies supported

  11. Magnetic resonance imaging in classification of congenital muscular dystrophies with brain abnormalities

    NARCIS (Netherlands)

    vanderKnaap, MS; Smit, LME; Barth, PG; CatsmanBerrevoets, CE; Brouwer, OF; Begeer, JH; deCoo, IFM; Valk, J.

    A survey was performed of magnetic resonance imaging (MRI) findings in 21 patients with congenital muscular dystrophy (QID) with cerebral abnormalities to evaluate the contribution of MRI to the classification of CMD patients. In 5 patients with Walker-Warburg syndrome (WWS), MRI showed

  12. Comparison of automated brain volumetry methods with stereology in children aged 2 to 3 years

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, Kristina N. [University Children' s Hospital of Zurich, Center for MR Research, Zurich (Switzerland); University Children' s Hospital, Pediatric Cardiology, Zurich (Switzerland); Latal, Beatrice [University Children' s Hospital, Child Development Center, Zurich (Switzerland); University Children' s Hospital, Children' s Research Center, Zurich (Switzerland); Knirsch, Walter [University Children' s Hospital, Pediatric Cardiology, Zurich (Switzerland); University Children' s Hospital, Children' s Research Center, Zurich (Switzerland); Scheer, Ianina [University Children' s Hospital, Department for Diagnostic Neuroradiology, Zurich (Switzerland); Rhein, Michael von [University Children' s Hospital, Child Development Center, Zurich (Switzerland); Reich, Bettina; Bauer, Juergen; Gummel, Kerstin [Justus-Liebig University, Pediatric Heart Center, University Hospital Giessen, Giessen (Germany); Roberts, Neil [University of Edinburgh, Clinical Research and Imaging Centre (CRIC), The Queens Medical Research Institute (QMRI), Edinburgh (United Kingdom); O' Gorman Tuura, Ruth [University Children' s Hospital of Zurich, Center for MR Research, Zurich (Switzerland); University Children' s Hospital, Children' s Research Center, Zurich (Switzerland)

    2016-09-15

    The accurate and precise measurement of brain volumes in young children is important for early identification of children with reduced brain volumes and an increased risk for neurodevelopmental impairment. Brain volumes can be measured from cerebral MRI (cMRI), but most neuroimaging tools used for cerebral segmentation and volumetry were developed for use in adults and have not been validated in infants or young children. Here, we investigate the feasibility and accuracy of three automated software methods (i.e., SPM, FSL, and FreeSurfer) for brain volumetry in young children and compare the measures with corresponding volumes obtained using the Cavalieri method of modern design stereology. Cerebral MRI data were collected from 21 children with a complex congenital heart disease (CHD) before Fontan procedure, at a median age of 27 months (range 20.9-42.4 months). Data were segmented with SPM, FSL, and FreeSurfer, and total intracranial volume (ICV) and total brain volume (TBV) were compared with corresponding measures obtained using the Cavalieri method. Agreement between the estimated brain volumes (ICV and TBV) relative to the gold standard stereological volumes was strongest for FreeSurfer (p < 0.001) and moderate for SPM segment (ICV p = 0.05; TBV p = 0.006). No significant association was evident between ICV and TBV obtained using SPM NewSegment and FSL FAST and the corresponding stereological volumes. FreeSurfer provides an accurate method for measuring brain volumes in young children, even in the presence of structural brain abnormalities. (orig.)

  13. Comparison of automated brain volumetry methods with stereology in children aged 2 to 3 years

    International Nuclear Information System (INIS)

    Mayer, Kristina N.; Latal, Beatrice; Knirsch, Walter; Scheer, Ianina; Rhein, Michael von; Reich, Bettina; Bauer, Juergen; Gummel, Kerstin; Roberts, Neil; O'Gorman Tuura, Ruth

    2016-01-01

    The accurate and precise measurement of brain volumes in young children is important for early identification of children with reduced brain volumes and an increased risk for neurodevelopmental impairment. Brain volumes can be measured from cerebral MRI (cMRI), but most neuroimaging tools used for cerebral segmentation and volumetry were developed for use in adults and have not been validated in infants or young children. Here, we investigate the feasibility and accuracy of three automated software methods (i.e., SPM, FSL, and FreeSurfer) for brain volumetry in young children and compare the measures with corresponding volumes obtained using the Cavalieri method of modern design stereology. Cerebral MRI data were collected from 21 children with a complex congenital heart disease (CHD) before Fontan procedure, at a median age of 27 months (range 20.9-42.4 months). Data were segmented with SPM, FSL, and FreeSurfer, and total intracranial volume (ICV) and total brain volume (TBV) were compared with corresponding measures obtained using the Cavalieri method. Agreement between the estimated brain volumes (ICV and TBV) relative to the gold standard stereological volumes was strongest for FreeSurfer (p < 0.001) and moderate for SPM segment (ICV p = 0.05; TBV p = 0.006). No significant association was evident between ICV and TBV obtained using SPM NewSegment and FSL FAST and the corresponding stereological volumes. FreeSurfer provides an accurate method for measuring brain volumes in young children, even in the presence of structural brain abnormalities. (orig.)

  14. Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

    Science.gov (United States)

    McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

    2017-11-01

    Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings

  15. Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

    Science.gov (United States)

    Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

    2016-07-01

    Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A brain network processing the age of faces.

    Directory of Open Access Journals (Sweden)

    György A Homola

    Full Text Available Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.

  17. Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

    Science.gov (United States)

    Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

    2016-11-01

    Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

  18. Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

    OpenAIRE

    Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

    2013-01-01

    Background Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical foc...

  19. Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

    Science.gov (United States)

    Ishii, Keisuke; Wada, Seiji; Takano, Mayumi; Nakata, Masahiko; Murakoshi, Takeshi; Sago, Haruhiko

    2018-02-20

    We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option. © 2018 S. Karger AG, Basel.

  20. Riboflavin-Responsive Multiple Acyl-CoA Dehydrogenase Deficiency Associated with Hepatoencephalomyopathy and White Matter Signal Abnormalities on Brain MRI.

    Science.gov (United States)

    Vieira, Päivi; Myllynen, Päivi; Perhomaa, Marja; Tuominen, Hannu; Keski-Filppula, Riikka; Rytky, Seppo; Risteli, Leila; Uusimaa, Johanna

    2017-06-01

    Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting both fatty acid and amino acid oxidation. It can manifest at any age, but riboflavin-responsiveness has mainly been described in less severely affected patients. We describe an infant with severe MADD presenting with profound hypotonia and hepatomegaly. Treatment with riboflavin improved his muscle strength, liver size, and biochemical markers. A homozygous mutation of electron transfer flavoprotein dehydrogenase ( ETFDH ) was found. His motor skills continued to progress until a fatal infection-triggered deterioration at the age of 34 months. We show changes in brain magnetic resonance imaging over the course of the disease, with profound white matter abnormalities during the deterioration phase. Aggregates of mitochondria with abnormal cristae in muscle electron microscopy were noticed already in infancy. An unusual lactate dehydrogenase (LDH) isoenzyme pattern with LDH-1 predominance was additionally observed. This case demonstrates riboflavin-responsiveness in a severely affected infant with both muscular and extramuscular involvement and further underlines the variable nature of this disease. Georg Thieme Verlag KG Stuttgart · New York.

  1. Association of a Guardian's Report of a Child Acting Abnormally With Traumatic Brain Injury After Minor Blunt Head Trauma.

    Science.gov (United States)

    Nishijima, Daniel K; Holmes, James F; Dayan, Peter S; Kuppermann, Nathan

    2015-12-01

    Increased use of computed tomography (CT) in children is concerning owing to the cancer risk from ionizing radiation, particularly in children younger than 2 years. A guardian report that a child is acting abnormally is a risk factor for clinically important traumatic brain injury (ciTBI) and may be a driving factor for CT use in the emergency department. To determine the prevalence of ciTBIs and TBIs in children younger than 2 years with minor blunt head trauma and a guardian report of acting abnormally with (1) no other findings or (2) other concerning findings for TBI. Secondary analysis of a large, prospective, multicenter cohort study that included 43 399 children younger than 18 years with minor blunt head trauma evaluated in 25 emergency departments. The study was conducted on data obtained between June 2004 and September 2006. Data analysis was performed between August 21, 2014, and March 9, 2015. A guardian report that the child was acting abnormally after minor blunt head trauma. The prevalence of ciTBI (defined as death, neurosurgery, intubation for >24 hours, or hospitalization for ≥2 nights in association with TBI on CT imaging) and TBI on CT imaging in children with a guardian report of acting abnormally with (1) no other findings and (2) other concerning findings for TBI. Of 43 399 children in the cohort study, a total of 1297 children had reports of acting abnormally, of whom 411 (31.7%) had this report as their only finding. Reported as percentage (95% CI), 1 of 411 (0.2% [0-1.3%]) had a ciTBI, and 4 TBIs were noted on the CT scans in 185 children who underwent imaging (2.2% [0.6%-5.4%]). In children with reports of acting abnormally and other concerning findings for TBI, 29 of 886 (3.3% [2.2%-4.7%]) had ciTBIs and 66 of 674 (9.8% [7.7%-12.3%]) had TBIs on CT. Clinically important TBIs are very uncommon, and TBIs noted on CT are uncommon in children younger than 2 years with minor blunt head trauma and guardian reports of the child acting

  2. Brain network characterization of high-risk preterm-born school-age children

    Directory of Open Access Journals (Sweden)

    Elda Fischi-Gomez

    2016-01-01

    Full Text Available Higher risk for long-term cognitive and behavioral impairments is one of the hallmarks of extreme prematurity (EP and pregnancy-associated fetal adverse conditions such as intrauterine growth restriction (IUGR. While neurodevelopmental delay and abnormal brain function occur in the absence of overt brain lesions, these conditions have been recently associated with changes in microstructural brain development. Recent imaging studies indicate changes in brain connectivity, in particular involving the white matter fibers belonging to the cortico-basal ganglia-thalamic loop. Furthermore, EP and IUGR have been related to altered brain network architecture in childhood, with reduced network global capacity, global efficiency and average nodal strength. In this study, we used a connectome analysis to characterize the structural brain networks of these children, with a special focus on their topological organization. On one hand, we confirm the reduced averaged network node degree and strength due to EP and IUGR. On the other, the decomposition of the brain networks in an optimal set of clusters remained substantially different among groups, talking in favor of a different network community structure. However, and despite the different community structure, the brain networks of these high-risk school-age children maintained the typical small-world, rich-club and modularity characteristics in all cases. Thus, our results suggest that brain reorganizes after EP and IUGR, prioritizing a tight modular structure, to maintain the small-world, rich-club and modularity characteristics. By themselves, both extreme prematurity and IUGR bear a similar risk for neurocognitive and behavioral impairment, and the here defined modular network alterations confirm similar structural changes both by IUGR and EP at school age compared to control. Interestingly, the combination of both conditions (IUGR + EP does not result in a worse outcome. In such cases, the alteration

  3. Acetyl-L-carnitine improves aged brain function.

    Science.gov (United States)

    Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

    2010-07-01

    The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

  4. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Brain surgery breathes new life into aging plants

    Energy Technology Data Exchange (ETDEWEB)

    Makansi, J. [Pearl Street Inc. (United States)

    2006-04-15

    Unlike managing the human aging process, extending the life of a power plant often includes brain surgery, modernizing its control and automation system. Lately, such retrofits range from wholesale replacing of existing controls to the addition of specific control elements that help optimize performance. Pending revisions to safety codes and cybersecurity issues also need to be considered. 4 figs.

  6. Effects of Age on Brain Development in Autism

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-09-01

    Full Text Available Total brain volumes were measured by MRI in 67 non-mentally retarded children with autism and 83 healthy controls, aged 8 to 46 years, in a study at University of Washington, Seattle: Johns Hopkins University Hospital, Baltimore: and University of Pittsburgh School of Medicine, PA.

  7. Obesity, dyslipidemia and brain age in first-episode psychosis

    Czech Academy of Sciences Publication Activity Database

    Kolenic, M.; Franke, K.; Hlinka, Jaroslav; Matějka, M.; Čapková, J.; Pausova, Z.; Uher, R.; Alda, M.; Španiel, F.; Hájek, T.

    2018-01-01

    Roč. 99, April (2018), s. 151-158 ISSN 0022-3956 Grant - others:GA MZd(CZ) NV16-32791A; GA MŠk(CZ) LO1611 Institutional support: RVO:67985807 Keywords : BrainAGE score * Dyslipidemia * First-episode psychosis * Obesity * Overweight * Schizophrenia Impact factor: 4.183, year: 2016

  8. Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

    Science.gov (United States)

    Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

    2017-01-01

    Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

  9. Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

    Science.gov (United States)

    Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

    2017-01-24

    Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

  10. Intrinsic brain connectivity related to age in young and middle aged adults.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    Full Text Available Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

  11. Life and death of neurons in the aging brain

    Science.gov (United States)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  12. Cranial computed tomography in aging of the brain

    International Nuclear Information System (INIS)

    Okudera, Hiroshi; Hara, Hideaki; Kobayashi, Shigeaki

    1988-01-01

    Computed tomography (CT) scans of 450 healthy persons were reviewed to examine aging of the brain. The subjects were divided according to age groups. Calcification of the choroid plexus and falx cerebri was associated with aging. The number of fissures, observed as an index of atrophy in the cerebral cortex, tended to increase with aging. There was no correlation between cella media index, which represents calcification in the cerebral artery and the size of the cerebral ventricle, and aging. Cella media index increased up to the age of 70; however, this was inverse in the 80 years or older age group. Cerebral arteriosclerosis and atrophied basilar nucleus of the cerebrum were supposed to be negative factors for living longer. Considering the two factors, persons in their seventies and eighties were divided into two groups. (Namekawa, K.)

  13. Structural and functional brain abnormalities place phenocopy frontotemporal dementia (FTD in the FTD spectrum

    Directory of Open Access Journals (Sweden)

    Rebecca M.E. Steketee

    2016-01-01

    Conclusion: PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum.

  14. Evolution of the aging brain transcriptome and synaptic regulation.

    Directory of Open Access Journals (Sweden)

    Patrick M Loerch

    Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

  15. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

    2008-11-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.

  16. Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available BACKGROUND: The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. METHODS AND FINDINGS: Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17 is characterised by a marked reduction in alpha (8-12 Hz power together with an enhancement in delta (1.5-4 Hz as compared to a normal hearing control group (n = 16. This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. CONCLUSIONS: Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus.

  17. Abnormal brain white matter network in young smokers: a graph theory analysis study.

    Science.gov (United States)

    Zhang, Yajuan; Li, Min; Wang, Ruonan; Bi, Yanzhi; Li, Yangding; Yi, Zhang; Liu, Jixin; Yu, Dahua; Yuan, Kai

    2018-04-01

    Previous diffusion tensor imaging (DTI) studies had investigated the white matter (WM) integrity abnormalities in some specific fiber bundles in smokers. However, little is known about the changes in topological organization of WM structural network in young smokers. In current study, we acquired DTI datasets from 58 male young smokers and 51 matched nonsmokers and constructed the WM networks by the deterministic fiber tracking approach. Graph theoretical analysis was used to compare the topological parameters of WM network (global and nodal) and the inter-regional fractional anisotropy (FA) weighted WM connections between groups. The results demonstrated that both young smokers and nonsmokers had small-world topology in WM network. Further analysis revealed that the young smokers exhibited the abnormal topological organization, i.e., increased network strength, global efficiency, and decreased shortest path length. In addition, the increased nodal efficiency predominately was located in frontal cortex, striatum and anterior cingulate gyrus (ACG) in smokers. Moreover, based on network-based statistic (NBS) approach, the significant increased FA-weighted WM connections were mainly found in the PFC, ACG and supplementary motor area (SMA) regions. Meanwhile, the network parameters were correlated with the nicotine dependence severity (FTND) scores, and the nodal efficiency of orbitofrontal cortex was positive correlation with the cigarette per day (CPD) in young smokers. We revealed the abnormal topological organization of WM network in young smokers, which may improve our understanding of the neural mechanism of young smokers form WM topological organization level.

  18. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  19. Comparative proteomic analysis of brains of naturally aging mice.

    Science.gov (United States)

    Yang, S; Liu, T; Li, S; Zhang, X; Ding, Q; Que, H; Yan, X; Wei, K; Liu, S

    2008-06-26

    We used comparative proteomic techniques to identify aging-related brain proteins in normal mice from neonate to old age. By 2-dimensional electrophoresis (2-DE), matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and peptide mass fingerprint (PMF) analysis, 39 proteins were identified, among which 6 stayed unchanged since 3 months, 6 increased and 27 decreased in various manners during aging. They are mainly involved in processes usually with destructive changes during aging, such as metabolism, transport, signaling, stress response and apoptosis. The 27 proteins' decrease may be responsible for brain aging. In particular, decrease of proteasome alpha subunits 3/6, ubiquitin carboxyl-terminal esterase L3, valosin-containing protein and calreticulin may be responsible for the declination of protein quality control; glutamate dehydrogenase 1, isocitrate dehydrogenase 1 and ubiquinol cytochrome c reductase core protein 2 for the shortage of energy and reducing agent; ubiquitin-conjugating enzyme E2N and heterogeneous nuclear ribonucleoprotein A2/B1 for the increase of DNA damage and transcription detuning; calbindin 1 and amphiphysin for the disturbance of synaptic transport and ion signals. The six proteins' increase may be involved in anti-aging processes. In particular, transketolase, mitochondrial creatine kinase 1 and ribosomal protein L37 may help to enhance energy metabolism; triosephosphate isomerase 1 may help to resist oxidative stress. Moreover, most of these proteins were found for the first time to be involved in the natural senescence of brain, which would provide new clues about the mechanism of brain aging.

  20. Neuron-astrocyte signaling is preserved in the aging brain.

    Science.gov (United States)

    Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

    2017-04-01

    Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley

  1. Abnormalities of Microcirculation and Intracranial and Cerebral Perfusion Pressures in Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2008-01-01

    Full Text Available Objective: to evaluate the states of microcirculation, cerebral perfusion intracranial pressures in patients with isolated severe brain injury (SBI and to determine their possible relationships. Subjects and methods. 148 studies were performed in 16 victims with SBI. According to the outcome of brain traumatic disease, the patients were divided into two groups: 1 those who had a good outcome (n=8 and 2 those who had a fatal outcome (n=8. Microcirculation was examined by skin laser Doppler flowmetry using a LAKK-01 capillary blood flow laser analyzer (LAZMA Research-and-Production Association, Russian Federation. All the victims underwent surgical interventions to remove epi-, subdural, and intracerebral hematomas. A Codman subdural/intraparenchymatous intracranial pressure (ICD sensor (Johnson & Johnson, United Kingdom was intraoperatively inserted in the victims. Cerebral perfusion pressure (CPP was calculated using the generally accepted formula: CPP = MBP (mean blood pressure — ICD. ICD, CPP, and microcirculation were studied on postoperative days 1, 3, 5, and 7. Their values were recorded simultaneously. Ninety and 58 studies were conducted in the group of patients with good and fatal outcomes, respectively. Results. No correlation between the changes in MBP, ICD, and microcirculatory parameters suggested that the value of ICD was determined by the nature of brain damage and it was the leading and determining indicator in the diagnosis and treatment of secondary cerebral lesions. The amplitude of low-frequency fluctuations directly correlated with ICD, which indicated that they might be used to evaluate cerebral perfusion and impaired cerebral circulation indirectly in victims with severe brain injury. Conclusion. The laser Doppler flowmetric technique makes it possible not only to qualitatively, but also quantitatively determine changes in the tissue blood flow system in severe brain injury. With this technique, both the local and central

  2. Open-access transvaginal sonography in women of reproductive age with abnormal vaginal bleeding: a descriptive study in general practice

    NARCIS (Netherlands)

    de Vries, Corlien J. H.; Wieringa-de Waard, Margreet; Bindels, Patrick J. E.; Ankum, Willem M.

    2011-01-01

    Diagnostic ultrasonography is used by GPs in approximately 10% of patients of reproductive age with abnormal vaginal bleeding. Transvaginal sonography is recommended as a first-line diagnostic instrument for assessing uterine pathology. To assess if findings resulting from open-access sonography

  3. Abnormal vaginal bleeding in women of reproductive age: a descriptive study of initial management in general practice

    NARCIS (Netherlands)

    de Vries, Corlien J. H.; Wieringa-de Waard, Margreet; Vervoort, Cléo-Lotte A. G.; Ankum, Willem M.; Bindels, Patrick J. E.

    2008-01-01

    BACKGROUND: Abnormal vaginal bleeding (AVB) in women of reproductive age is a common reason for consulting a general practitioner. Nevertheless, how general practitioners (GPs) choose to initially manage AVB is largely unknown, as is the prevalence of underlying pathology of AVB in primary care.

  4. Aging and gene expression in the primate brain.

    Directory of Open Access Journals (Sweden)

    Hunter B Fraser

    2005-09-01

    Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  5. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  6. Clinical study on brain tumors in the aged

    International Nuclear Information System (INIS)

    Teramoto, Akira; Manaka, Shinya; Takakura, Kintomo

    1981-01-01

    In order to investigate the clinical features and the prognosis of brain tumors in the aged, 132 cases over 60 years of age were studied from the consecutive series of 1,793 brain tumors in the University of Tokyo Hospital (1963 - 1979). The incidence of brain tumors in the aged was 7.4% on the whole, while it showed a significant increase from 4.8% (1960's) to 11.5% (the later half of 1970's). Histologically, meningiomas were the most common tumors (26%), followed by neurinomas (17%), pituitary adenomas (16%) and metastatic tumors (15%). Malignant gliomas were found more frequently than benign ones. There were more meningiomas as age advanced. The proportion and the number of meningioma cases has obviously increased in recent years when CT scanners became available. Symptoms of intracranial hypertention were found less frequently in aged patients although they were still common in cases of glioblastomas. The duration from onset to surgery was relatively long, especially in cases of neurinomas and pituitary adenomas. Two cases of astrocytomas belonged to the category of silent gliomas. Overall operative mortality rate was 10.6%, while it showed a marked decrease to 4.7% in the 1970's. Five-year survival rates were as follows: meningiomas (58%), pituitary adenomas (70%), neurinomas (80%), glioblastomas (20%) and astrocytomas (25%). As for functional prognoses, 30% of the patients showed poor states on ADL, mostly because of residual psychic disorders. (author)

  7. Age-dependent complex noise fluctuations in the brain

    International Nuclear Information System (INIS)

    Mareš, Jan; Vyšata, Oldřich; Procházka, Aleš; Vališ, Martin

    2013-01-01

    We investigated the parameters of colored noise in EEG data of 17 722 professional drivers aged 18–70. The whole study is based upon experiments showing that biological neural networks may operate in the vicinity of the critical point and that the balance between excitation and inhibition in the human brain is important for the transfer of information. This paper is devoted to the study of EEG power spectrum which can be described best by a power function with 1/f λ distribution and colored noise corresponding to the critical point in the EEG signal has the value of λ = 1 (purple noise). The slow accumulation of energy and its quick release is a universal property of the 1/f distribution. The physiological mechanism causing energy dissipation in the brain seems to depend on the number and strength of the connections between clusters of neurons. With ageing, the number of connections between the neurons decreases. Learning ability and intellectual performance also decrease. Therefore, age-related changes in the λ coefficient can be anticipated. We found that absolute values of λ coefficients decrease significantly with increasing age. Deviations from this rule are related to age-dependent slowing of the dominant frequency in the alpha band. Age-dependent change in the parameter and colored noise may be indicative of age-related changes in the self-organization of brain activity. Results obtained include (i) the age-dependent decrease of the absolute values of the average λ coefficient with the regression coefficient 0.005 1/year, (ii) distribution of λ value changes related to EEG frequency bands and to localization of electrodes on the scalp, and (iii) relation of age-dependent changes of colored noise and EEG energy in separate frequency bands. (paper)

  8. Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging.

    Science.gov (United States)

    Hayakawa, Yayoi K; Sasaki, Hiroki; Takao, Hidemasa; Mori, Harushi; Hayashi, Naoto; Kunimatsu, Akira; Aoki, Shigeki; Ohtomo, Kuni

    2013-01-25

    Brain structural changes accompany major depressive disorder, but whether subclinical depression is accompanied by similar changes in brain volume and white matter integrity is unknown. By using voxel-based morphometry (VBM) of the gray matter and tract-specific analysis based on diffusion tensor imaging (DTI) of the white matter, we explored the extent to which abnormalities could be identified in specific brain structures of healthy adults with subclinical depression. The subjects were 21 community-dwelling adults with subclinical depression, as measured by their Center for Epidemiologic Studies Depression Scale (CES-D) scores. They were not demented and had no neurological or psychiatric history. We collected brain magnetic resonance images of the patients and of 21 matched control subjects, and we used VBM to analyze the differences in regional gray matter volume between the two groups. Moreover, we examined the white matter integrity by using tract-specific analysis based on the gray matter volume changes revealed by VBM. VBM revealed that the volumes of both anterior cingulate gyri and the right rectal gyrus were smaller in subclinically depressed women than in control women. Calculation of DTI measures in the anterior cingulum bundle revealed a positive correlation between CES-D scale score and radial diffusivity in the right anterior cingulum in subclinically depressed women. The small sample size limits the stability of the reported findings. Gray matter volume reduction and white matter integrity change in specific frontal brain regions may be associated with depressive symptoms in women, even at a subclinical level. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Tobacco Smoking and MRI/MRS Brain Abnormalities Compared to Nonsmokers

    OpenAIRE

    Domino, E.F.

    2008-01-01

    This mini review emphasizes the fact that tobacco smoking causes small but real biologic brain changes that need to be studied in depth. A crucial question is whether these anatomical/chemical changes reverse toward normal when smokers quit. This review is presented to stimulate further research to answer this question.

  10. Running in the family? : structural brain abnormalities in first-degree relatives of patients with schizophrenia

    NARCIS (Netherlands)

    Boos, H.B.M.

    2011-01-01

    The studies conducted in this thesis explored brain structures in first-degree relatives of patients with schizophrenia. The meta-analysis that Boos and colleagues performed showed that relatives of patients with schizophrenia had smaller hippocampal volumes, smaller gray matter volumes and larger

  11. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    Science.gov (United States)

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  12. Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

    OpenAIRE

    Hughes, J R; Bowes, S G; Leeman, A L; O'Neill, C J; Deshmukh, A A; Nicholson, P W; Dobbs, S M; Dobbs, R J

    1990-01-01

    1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes w...

  13. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    Science.gov (United States)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  14. Abnormal findings of magnetic resonance imaging (MRI) in patients with systemic lupus erythematosus involving the brain

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Akira; Okada, Jun; Kondo, Hirobumi (Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine); Kashiwazaki, Sadao

    1992-06-01

    To elucidate the clinical significance of MRI on central nervous system systemic lupus erythematosus (CNS-SLE), MRI and CT scans were performed in 35 patients with SLE, of 18 patients who had CNS manifestations at the time of MRI examinations. The investigations were also carried out in 17 patients without CNS-SLE. The rate of detection of abnormal findings on MRI in patients with CNS-SLE was 77.2% (14/18), which was high, as compared with the rate of those on CT scans (50%: 9/18). Especially, all of 4 patients with seizure and 3 patients with encephalopathy showed abnormal MRI findings, although respectively 50% and 33.3% of them had abnormal CT scan findings. MRI findings were classified into 4 groups below: (1) Large focal are as increased signal intensity at T2 weighted image. These were observed in 2 of 4 patients with seizure and 1 of 3 patients with encephalopathy, which were completely resolved after treatment. (2) Patchy subcortical foci of increased signal intensity at T2 weighted image. These were observed in 11 of 18 CNS-SLE and 7 of 17 without CNS-SLE, which were not detected by CT scan. (3) All of six patients with cerebral infarctions showed high signal intensity areas at T2 weighted image and low signal intensity areas at T1 weighted image. (4) Normal findings were observed in 4 of 18 CNS-SLE (22.2%). We concluded that MRI is useful for the evaluation of CNS-SLE and provides more information than CT scan. (author).

  15. Abnormal findings of magnetic resonance imaging (MRI) in patients with systemic lupus erythematosus involving the brain

    International Nuclear Information System (INIS)

    Ishikawa, Akira; Okada, Jun; Kondo, Hirobumi; Kashiwazaki, Sadao.

    1992-01-01

    To elucidate the clinical significance of MRI on central nervous system systemic lupus erythematosus (CNS-SLE), MRI and CT scans were performed in 35 patients with SLE, of 18 patients who had CNS manifestations at the time of MRI examinations. The investigations were also carried out in 17 patients without CNS-SLE. The rate of detection of abnormal findings on MRI in patients with CNS-SLE was 77.2% (14/18), which was high, as compared with the rate of those on CT scans (50%: 9/18). Especially, all of 4 patients with seizure and 3 patients with encephalopathy showed abnormal MRI findings, although respectively 50% and 33.3% of them had abnormal CT scan findings. MRI findings were classified into 4 groups below: 1) Large focal are as increased signal intensity at T2 weighted image. These were observed in 2 of 4 patients with seizure and 1 of 3 patients with encephalopathy, which were completely resolved after treatment. 2) Patchy subcortical foci of increased signal intensity at T2 weighted image. These were observed in 11 of 18 CNS-SLE and 7 of 17 without CNS-SLE, which were not detected by CT scan. 3) All of six patients with cerebral infarctions showed high signal intensity areas at T2 weighted image and low signal intensity areas at T1 weighted image. 4) Normal findings were observed in 4 of 18 CNS-SLE (22.2%). We concluded that MRI is useful for the evaluation of CNS-SLE and provides more information than CT scan. (author)

  16. Whole brain approaches for identification of microstructural abnormalities in individual patients: comparison of techniques applied to mild traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Namhee Kim

    Full Text Available Group-wise analyses of DTI in mTBI have demonstrated evidence of traumatic axonal injury (TAI, associated with adverse clinical outcomes. Although mTBI is likely to have a unique spatial pattern in each patient, group analyses implicitly assume that location of injury will be the same across patients. The purpose of this study was to optimize and validate a procedure for analysis of DTI images acquired in individual patients, which could detect inter-individual differences and be applied in the clinical setting, where patients must be assessed as individuals.After informed consent and in compliance with HIPAA, 34 mTBI patients and 42 normal subjects underwent 3.0 Tesla DTI. Four voxelwise assessment methods (standard Z-score, "one vs. many" t-test, Family-Wise Error Rate control using pseudo t-distribution, EZ-MAP for use in individual patients, were applied to each patient's fractional anisotropy (FA maps and tested for its ability to discriminate patients from controls. Receiver Operating Characteristic (ROC analyses were used to define optimal thresholds (voxel-level significance and spatial extent for reliable and robust detection of mTBI pathology.ROC analyses showed EZ-MAP (specificity 71%, sensitivity 71%, "one vs. many" t-test and standard Z-score (sensitivity 65%, specificity 76% for both methods resulted in a significant area under the curve (AUC score for discriminating mTBI patients from controls in terms of the total number of abnormal white matter voxels detected while the FWER test was not significant. EZ-MAP is demonstrated to be robust to assumptions of Gaussian behavior and may serve as an alternative to methods that require strict Gaussian assumptions.EZ-MAP provides a robust approach for delineation of regional abnormal anisotropy in individual mTBI patients.

  17. Inconsistency in Abnormal Brain Activity across Cohorts of ADHD-200 in Children with Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Wang, Jian-Bao; Zheng, Li-Jun; Cao, Qing-Jiu; Wang, Yu-Feng; Sun, Li; Zang, Yu-Feng; Zhang, Hang

    2017-01-01

    Many papers have shown results from the multi-site dataset of resting-state fMRI (rs-fMRI) in attention deficit hyperactivity disorder (ADHD), a data-sharing project named ADHD-200. However, few studies have illustrated that to what extent the pooled findings were consistent across cohorts. The present study analyzed three voxel-wise whole-brain metrics, i.e., amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) based on the pooled dataset as well as individual cohort of ADHD-200. In addition to the conventional frequency band of 0.01-0.08 Hz, sub-frequency bands of 0-0.01, 0.01-0.027, 0.027-0.073, 0.073-0.198, and 0.198-0.25 Hz, were assessed. While the pooled dataset showed abnormal activity in some brain regions, e.g., the bilateral sensorimotor cortices, bilateral cerebellum, and the bilateral lingual gyrus, these results were highly inconsistent across cohorts, even across the three cohorts from the same research center. The standardized effect size was rather small. These findings suggested a high heterogeneity of spontaneous brain activity in ADHD. Future studies based on multi-site large-sample dataset should be performed on pooled data and single cohort data, respectively and the effect size must be shown.

  18. Effect of contrast leakage on the detection of abnormal brain tumor vasculature in high-grade glioma.

    Science.gov (United States)

    LaViolette, Peter S; Daun, Mitchell K; Paulson, Eric S; Schmainda, Kathleen M

    2014-02-01

    Abnormal brain tumor vasculature has recently been highlighted by a dynamic susceptibility contrast (DSC) MRI processing technique. The technique uses independent component analysis (ICA) to separate arterial and venous perfusion. The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially occurs in brain tumors and predicts response to anti-angiogenic therapy. The effects of contrast agent leakage on the AVOL biomarker have yet to be established. DSC was acquired during two separate contrast boluses in ten patients undergoing clinical imaging for brain tumor diagnosis. Three components were modeled with ICA, which included the arterial and venous components. The percentage of each component as well as a third component were determined within contrast enhancing tumor and compared. AVOL within enhancing tumor was also compared between doses. The percentage of enhancing tumor classified as not arterial or venous and instead into a third component with contrast agent leakage apparent in the time-series was significantly greater for the first contrast dose compared to the second. The amount of AVOL detected within enhancing tumor was also significantly greater with the second dose compared to the first. Contrast leakage results in large signal variance classified as a separate component by the ICA algorithm. The use of a second dose mitigates the effect and allows measurement of AVOL within enhancement.

  19. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    Directory of Open Access Journals (Sweden)

    Kimberly B Zumbrennen-Bullough

    Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  20. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.

    Science.gov (United States)

    Bourre, J M

    2004-01-01

    results have shown that dietary alpha-linolenic acid deficiency induces more marked abnormalities in certain cerebral structures than in others, as the frontal cortex and pituitary gland are more severely affected. These selective lesions are accompanied by behavioural disorders more particularly affecting certain tests (habituation, adaptation to new situations). Biochemical and behavioural abnormalities are partially reversed by a dietary phospholipid supplement, especially omega-3-rich egg yolk extracts or pig brain. A dose-effect study showed that animal phospholipids are more effective than plant phospholipids to reverse the consequences of alpha-linolenic acid deficiency, partly because they provide very long preformed chains. Alpha-linolenic acid deficiency decreases the perception of pleasure, by slightly altering the efficacy of sensory organs and by affecting certain cerebral structures. Age-related impairment of hearing, vision and smell is due to both decreased efficacy of the parts of the brain concerned and disorders of sensory receptors, particularly of the inner ear or retina. For example, a given level of perception of a sweet taste requires a larger quantity of sugar in subjects with alpha-linolenic acid deficiency. In view of occidental eating habits, as omega-6 fatty acid deficiency has never been observed, its impact on the brain has not been studied. In contrast, omega-9 fatty acid deficiency, specifically oleic acid deficiency, induces a reduction of this fatty acid in many tissues, except the brain (but the sciatic nerve is affected). This fatty acid is therefore not synthesized in sufficient quantities, at least during pregnancy-lactation, implying a need for dietary intake. It must be remembered that organization of the neurons is almost complete several weeks before birth, and that these neurons remain for the subject's life time. Consequently, any disturbance of these neurons, an alteration of their connections, and impaired turnover of their

  1. Demonstration of cerebral abnormalities in cocaine abusers with SPECT perfusion brain scans

    International Nuclear Information System (INIS)

    Nagel, J.S.; Tumeh, S.S.; English, R.J.; Moore, M.; Lee, V.W.; Holman, L.B.

    1989-01-01

    This paper reports I-123 isopropyl iodoamphetamine (IMP) single-photon emission CT (SPECT) brain scans performed on cocaine users to investigate the effects of cocaine on the cerebral perfusion in a manner similar to previous CT, angiographic and positron-emission tomographic (PET) studies. Ten asymptomatic or mildly symptomatic cocaine users, two users with major neurovascular complications, and five normal subjects were studied with IMP SPECT. Rotating-brain images of the cerebral IMP uptake were displayed by using a distance-weighted surface-projection technique and were visually analyzed for focal cortical perfusion deficits. Eleven cocaine users had multiple scattered cortical IMP defects. Frontal lobe defects were most prominent. One user had confluent defects resembling swiss cheese. Concurrent CT scans available in nine patients were negative in seven and showed infarcts in two. No similar focal findings were visible in normals

  2. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    OpenAIRE

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2007-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images.

  3. Brain metabolism in health, aging, and neurodegeneration.

    Science.gov (United States)

    Camandola, Simonetta; Mattson, Mark P

    2017-06-01

    Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  4. MRI study of the brain in aged volunteers

    International Nuclear Information System (INIS)

    Kasahara, Hiroo; Tanno, Munehiko; Yamada, Hideo; Endoh, Kazuo; Kobayashi, Mitsuru; Karasawa, Akihide.

    1993-01-01

    In order to characterize age-related and chronological changes of the brain, longitudinal studies of aged volunteers were conducted using computed tomography since 1982. The present paper discusses correlations between brain function and findings of MR images which were obtained using a 1.5 T superconductive MR instrument since 1989. A total of 118 volunteers aged 60 to 88 years old with a mean age of 75.0±6.7 participated in the study, which consisted of MRI, EEG recording, the Benton Visual Retention Test and a medical interview. Subjects with a past history or clinical evidence of CVD, head trauma or dementia were excluded from the study. Incidence of T 2 high signal intensity lesions increased with age. Some showing T 1 low signal intensity in the same lesion were considered to be lacunar infarction, over all incidence of which was 24.6%. Numbers of correct responses on the BVRT showed a negative correlation with numbers of T 2 high signal intensity lesions. Although the aged volunteers in the present study could achieve all activity of daily living without any trouble, high cortical function evaluated by visuoperceptual performance of BVRT was somewhat disturbed in participants with multiple T 2 high signal intensity lesions. Brain atrophy seems to be more advanced in groups with T 2 hyper intensity lesions than in the group without them. These findings may support the notion that T 2 high signal intensity lesions are not merely an index of aging but pathologic lesions accompanied with senescence, although further studies including clinico-pathological correlation are necessary to establish this concept. (author)

  5. The medical management of abnormal uterine bleeding in reproductive-aged women.

    Science.gov (United States)

    Bradley, Linda D; Gueye, Ndeye-Aicha

    2016-01-01

    In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

    Science.gov (United States)

    Chow, Maggie L; Pramparo, Tiziano; Winn, Mary E; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J; Courchesne, Eric

    2012-01-01

    Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons

  7. Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

    Directory of Open Access Journals (Sweden)

    Maggie L Chow

    Full Text Available Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess

  8. Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages

    Science.gov (United States)

    Winn, Mary E.; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J.; Courchesne, Eric

    2012-01-01

    Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons

  9. A small number of abnormal brain connections predicts adult autism spectrum disorder.

    Science.gov (United States)

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez, José E; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-04-14

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.

  10. Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome.

    Science.gov (United States)

    Gu, Li-Na; Zhang, Min; Zhu, Hui; Liu, Jing-Yao

    2016-10-01

    Neuromyelitis optica spectrum disorder often co-exists with primary Sjögren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with ( n = 6) or without primary Sjögren's syndrome ( n = 10). All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sjögren's-syndrome-related antigen A antibodies, anti-Sjögren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjögren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% (4/6) of patients with primary Sjögren's syndrome and in 60% (6/10) of patients without primary Sjögren's syndrome. More brain abnormalities were observed in patients without primary Sjögren's syndrome than in those with primary Sjögren's syndrome. Segments lesions (> 3 centrum) were noted in 50% (5/10) of patients without primary Sjögren's syndrome and in 67% (4/6) of patients with primary Sjögren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome have a high frequency of brain abnormalities.

  11. Late-life depression: structural brain abnormalities, treatment and risk factors

    NARCIS (Netherlands)

    Janssen, Joost

    2006-01-01

    Major depression is a prevalent disease among the elderly, significantly decreasing the quality of life. The age of first onset of depression can be early in life, so called early-onset depression (EOD), as well as first occur in old age, i.e. late-onset depression (LOD). Some previous studies have

  12. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

    Science.gov (United States)

    Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P; Strosznajder, Joanna B

    2017-03-01

    Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD + levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD + -dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

  13. Brain Plasticity and Motor Practice in Cognitive Aging

    Directory of Open Access Journals (Sweden)

    Liuyang eCai

    2014-03-01

    Full Text Available For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

  14. Abnormalities of brain response during encoding into verbal working memory among euthymic patients with bipolar disorder.

    Science.gov (United States)

    McKenna, Benjamin S; Sutherland, Ashley N; Legenkaya, Anna P; Eyler, Lisa T

    2014-05-01

    Individuals with bipolar disorder (BD) have trait-like deficits in attention and working memory (WM). A fundamental dissociation for most verbal WM theories involves the separation of sensory-perceptual encoding, reliant upon attention, from the maintenance of this information in WM proper. The present study examined if patients with BD demonstrate differential neural changes in encoding and maintenance WM processes that underlie cognitive impairment. Event-related functional magnetic resonance imaging during a delayed match-to-sample WM paradigm was employed in 23 inter-episode medicated patients with BD and 23 demographically similar healthy comparison participants. We examined brain regions during encoding and maintenance task intervals to identify regions that demonstrated differential effects between groups. Medication effects and functional connectivity between prefrontal cortex and basal ganglia/thalamus were examined during the encoding interval due to the importance of these regions and the connection among them for encoding into WM. Patients with BD exhibited deficits in task accuracy and attenuated brain response during the encoding interval in areas of the prefrontal cortex, caudate, thalamus, and posterior visual regions. In contrast, patients with BD exhibited hyperactivation in posterior sensory regions during the maintenance interval. Among the BD group, those with greater medication load exhibited the greatest brain response within the prefrontal cortex. Reduction in activation during the encoding interval suggests that attentional deficits underlie WM deficits in patients with BD. These deficits appear to be trait-like in so far as they were observed during periods of euthymia in patients with BD. Medication effects remain to be further explored as there was evidence of prefrontal changes dependent on medication load. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Neurovascular abnormalities in brain disorders: highlights with angiogenesis and magnetic resonance imaging studies.

    Science.gov (United States)

    Chen, Chiao-Chi V; Chen, Yu-Chen; Hsiao, Han-Yun; Chang, Chen; Chern, Yijuang

    2013-07-05

    The coupling between neuronal activity and vascular responses is controlled by the neurovascular unit (NVU), which comprises multiple cell types. Many different types of dysfunction in these cells may impair the proper control of vascular responses by the NVU. Magnetic resonance imaging, which is the most powerful tool available to investigate neurovascular structures or functions, will be discussed in the present article in relation to its applications and discoveries. Because aberrant angiogenesis and vascular remodeling have been increasingly reported as being implicated in brain pathogenesis, this review article will refer to this hallmark event when suitable.

  16. Increased self-diffusion of brain water in normal aging

    DEFF Research Database (Denmark)

    Gideon, P; Thomsen, C; Henriksen, O

    1994-01-01

    With magnetic resonance (MR) imaging, brain water self-diffusion was measured in 17 healthy volunteers 22-76 (mean, 44.6) years old. The calculated values for the apparent diffusion coefficients (ADCs) ranged from 0.58 x 10(-9) to 1.23 x 10(-9) m2/sec in cerebral white matter. A significant...... by an increase in the extracellular volume due to age-dependent neuronal degeneration or to changes in myelination. These findings have implications for future clinical investigations with diffusion MR imaging techniques in patients with neurologic diseases, and stress the importance of having an age...

  17. Abnormal baseline brain activity in Parkinson's disease with and without REM sleep behavior disorder: A resting-state functional MRI study.

    Science.gov (United States)

    Li, Dan; Huang, Peiyu; Zang, Yufeng; Lou, Yuting; Cen, Zhidong; Gu, Quanquan; Xuan, Min; Xie, Fei; Ouyang, Zhiyuan; Wang, Bo; Zhang, Minming; Luo, Wei

    2017-09-01

    To investigate the differences in spontaneous brain activity between Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD), PD patients without RBD, and normal controls, which may shed new light on the neural mechanism of RBD. Eighteen PD patients with RBD, 16 patients without RBD, and 19 age- and gender-matched normal controls underwent clinical assessment and functional magnetic resonance imaging (fMRI) with a 3.0T scanner. Resting-state fMRI scans were collected using an echo planar imaging sequence. Amplitude of low-frequency fluctuations (ALFF) were calculated to measure spontaneous brain activity in each subject. Compared with PD patients without RBD, patients with RBD exhibited significantly decreased ALFF values (P abnormalities. Our findings provide additional insight into the neural mechanism of RBD and may drive future research to develop better treatment. 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:697-703. © 2016 International Society for Magnetic Resonance in Medicine.

  18. Age and Gender Effects On Auditory Brain Stem Response (ABR

    Directory of Open Access Journals (Sweden)

    Yones Lotfi

    2012-10-01

    Full Text Available Objectives: Auditory Brain Stem Response (ABR is a result of eight nerve and brain stem nuclei stimulation. Several factors may affect the latencies, interpeak latencies and amplitudes in ABR especially sex and age. In this study, age and sex influence on ABR were studied. Methods: This study was performed on 120 cases (60 males and 60 females at Akhavan rehabilitation center of university of welfare and rehabilitation sciences, Tehran, Iran. Cases were divided in three age groups: 18-30, 31-50 and 51-70 years old. Each age group consists of 20 males and 20 females. Age and sex influences on absolute latency of wave I and V, and IPL of I-V were examined. Results: Independent t test showed that females have significantly shorter latency of wave I, V, and IPL I-V latency (P<0.001 than males. Two way ANOVA showed that latency of wave I, V and IPL I-V in 51-70 years old group was significantly higher than 18-30 and 31-50 years old groups (P<0.001 Discussion: According to the results of present study and similar studies, in clinical practice, different norms for older adults and both genders should be established.

  19. The neuro-radiological anatomy of the normal and abnormal rat brain

    International Nuclear Information System (INIS)

    Schumacher, M.; Doller, P.; Voigt, K.

    1979-01-01

    In vivo and post mortem techniques for the radiological examination of normal brains have been developed, using 66 white adult rats. Aortic arch injections for survey angiograms (10 animals), selective catheterisation of the internal carotid artery (16 animals) and ventriculography by percutaneous needle puncture (20 animals) were performed in vivo; the animals survived and the examinations could be repeated. The techniques proved useful and accurate methods for the radiological demonstration of the topography and morphology of cerebral vessels and chambers; they also provided information on the function of the cerebral circulation and C.S.F. dynamics. The findings were checked and correlated by post mortem studies (20 animals) using contact radiography, micro-angiography and casts of the ventricles. As a result, extensive topographic and anatomic information concerning the cerebral vessels in the rat was obtained, including some microscopic-radiological findings. The combined use of these methods provided a basis for studying the growth of experimentally induced brain tumours and the effect of various types of treatment. (orig.) [de

  20. Age-dependent effects of brain stimulation on network centrality

    DEFF Research Database (Denmark)

    Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus

    2018-01-01

    Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task......-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age associated differential neural tDCS effects. Three “online” tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30...... characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing...

  1. Development and aging of a brain neural stem cell niche.

    Science.gov (United States)

    Conover, Joanne C; Todd, Krysti L

    2017-08-01

    In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Challenges of multimorbidity of the aging brain: a critical update.

    Science.gov (United States)

    Jellinger, Kurt A; Attems, Johannes

    2015-04-01

    A major problem in elderly patients is the high incidence of multiple pathologies, referred to as multimorbidity, in the aging brain. It has been increasingly recognized that co-occurrence of neurodegenerative proteinopathies and other pathologies including cerebrovascular disorders is a frequent event in the brains of both cognitively intact and impaired aged subjects. Although clinical and neuropathological diagnostic criteria of the major neurodegenerative diseases have been improved, major challenges arise from cerebral multimorbidity, and the thresholds to cause clinical overt dementia are ill defined. More than 80% of aged human brains show neurodegenerative non-Alzheimer type proteinopathies and other pathologies which, however, frequently have been missed clinically and are even difficult to identify at neuropathological examination. Autopsy studies differ in selection criteria and the applied evaluation methods. Therefore, irrespective of the clinical symptoms, the frequency of cerebral pathologies vary considerably: Alzheimer-related pathology is seen in 19-100%, with "pure" Alzheimer's disease (AD) in 17-72%, Lewy pathology in 6-39% (AD + Lewy disease 9-28%), vascular pathologies in 28-93% (10.7-78% "pure" vascular dementia), TDP-43 proteinopathy in 6-39%, hippocampal sclerosis in 8-1%, and mixed pathologies in 10-93%. These data clearly suggest that pathologically deposited proteins in neurodegenerating diseases mutually interact and are influenced by other factors, in particular cardiovascular and cerebrovascular ones, to promote cognitive decline and other clinical symptoms. It is obvious that cognitive and other neuropsychiatric impairment in the aged result from a multimorbid condition in the CNS rather than from a single disease and that the number of complex pathologies progresses with increasing age. These facts have implications for improvement of the clinical diagnosis and prognosis, the development of specific biomarkers, preventive strategies

  3. Brain structural abnormalities in behavior therapy-resistant obsessive-compulsive disorder revealed by voxel-based morphometry

    Directory of Open Access Journals (Sweden)

    Hashimoto N

    2014-10-01

    Full Text Available Nobuhiko Hashimoto,1 Shutaro Nakaaki,2 Akiko Kawaguchi,1 Junko Sato,1 Harumasa Kasai,3 Takashi Nakamae,4 Jin Narumoto,4 Jun Miyata,5 Toshi A Furukawa,6,7 Masaru Mimura2 1Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 3Department of Central Radiology, Nagoya City University Hospital, Nagoya, Japan; 4Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 5Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 6Department of Health Promotion and Human Behavior, 7Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan Background: Although several functional imaging studies have demonstrated that behavior therapy (BT modifies the neural circuits involved in the pathogenesis of obsessive-compulsive disorder (OCD, the structural abnormalities underlying BT-resistant OCD remain unknown. Methods: In this study, we examined the existence of regional structural abnormalities in both the gray matter and the white matter of patients with OCD at baseline using voxel-based morphometry in responders (n=24 and nonresponders (n=15 to subsequent BT. Three-dimensional T1-weighted magnetic resonance imaging was performed before the completion of 12 weeks of BT. Results: Relative to the responders, the nonresponders exhibited significantly smaller gray matter volumes in the right ventromedial prefrontal cortex, the right orbitofrontal cortex, the right precentral gyrus, and the left anterior cingulate cortex. In addition, relative to the responders, the nonresponders exhibited significantly smaller white matter volumes in the left cingulate bundle and the left superior frontal white matter. Conclusion: These results suggest that the brain

  4. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    Science.gov (United States)

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Facial Emotion Recognition Impairments are Associated with Brain Volume Abnormalities in Individuals with HIV

    Science.gov (United States)

    Clark, Uraina S.; Walker, Keenan A.; Cohen, Ronald A.; Devlin, Kathryn N.; Folkers, Anna M.; Pina, Mathew M.; Tashima, Karen T.

    2015-01-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV− associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities. PMID:25744868

  6. Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin.

    Science.gov (United States)

    Eisenblätter, Anneka; Lewis, Richard; Dörfler, Arnd; Forster, Clemens; Zimmermann, Katharina

    2017-01-01

    Cold allodynia occurs as a major symptom of neuropathic pain states. It remains poorly treated with current analgesics. Ciguatoxins (CTXs), ichthyosarcotoxins that cause ciguatera, produce a large peripheral sensitization to dynamic cold stimuli in Aδ-fibers by activating sodium channels without producing heat or mechanical allodynia. We used CTXs as a surrogate model of cold allodynia to dissect the framework of cold allodynia-activated central pain pathways. Reversible cold allodynia was induced in healthy male volunteers by shallow intracutaneous injection of low millimolar concentrations of CTX into the dorsal skin of the forefoot. Cold and warm stimuli were delivered to the treated and the control site using a Peltier-driven thermotest device. Functional magnetic resonance imaging (fMRI) scans were acquired with a 3T MRI scanner using a blood oxygen level-dependent (BOLD) protocol. The CTX-induced substantial peripheral sensitization to cooling stimuli in Aδ-fibers is particularly retrieved in BOLD changes due to dynamic temperature changes and less during constant cooling. Brain areas that responded during cold allodynia were almost always located bilaterally and appeared in the medial insula, medial cingulate cortex, secondary somatosensory cortex, frontal areas, and cerebellum. Whereas these areas also produced changes in BOLD signal during the dynamic warming stimulus on the control site, they remained silent during the warming stimuli on the injected site. We describe the defining feature of the cold allodynia pain percept in the human brain and illustrate why ciguatera sufferers often report a perceptual temperature reversal. ANN NEUROL 2017;81:104-116. © 2016 American Neurological Association.

  7. Protective Effects of Flax Seed (Linum Usitatissimum) Hydroalcoholic Extract on Fetus Brain in Aged and Young Mice.

    Science.gov (United States)

    Kamali, Mahsa; Bahmanpour, Soghra

    2016-05-01

    One of the major problems of the aged women or older than 35 is getting pregnant in the late fertility life. Fertility rates begin to decline gradually at the age of 30, more so at 35, and markedly at 40. Even with fertility treatments such as in vitro fertilization, women have more difficulty in getting pregnant or may deliver abnormal fetus. The purpose of this study was to assess the effects of flax seed hydroalcoholic extract on the fetal brain of aged mice and its comparison with young mice. In this experimental study, 32 aged and 32 young mice were divided into 4 groups. Controls received no special treatment. The experimental mice groups, 3 weeks before mating, were fed with flax seed hydroalcoholic extract by oral gavages. After giving birth, the brains of the fetus were removed. Data analysis was performed by statistical test ANOVA using SPSS version 18 (P<0.05). The mean fetus brain weight of aged mother groups compared to the control group was increased significantly (P<0.05). This study showed that flax seed hydroalcoholic extract could improve fetal brain weights in the aged groups.

  8. Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain Injury Are Partially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189.

    Science.gov (United States)

    Liu, Yu; McAfee, Samuel S; Guley, Natalie M; Del Mar, Nobel; Bu, Wei; Heldt, Scott A; Honig, Marcia G; Moore, Bob M; Reiner, Anton; Heck, Detlef H

    2017-01-01

    Mild traumatic brain injury (mTBI) can cause severe long-term cognitive and emotional deficits, including impaired memory, depression, and persevering fear, but the neuropathological basis of these deficits is uncertain. As medial prefrontal cortex (mPFC) and hippocampus play important roles in memory and emotion, we used multi-site, multi-electrode recordings of oscillatory neuronal activity in local field potentials (LFPs) in awake, head-fixed mice to determine if the functioning of these regions was abnormal after mTBI, using a closed-skull focal cranial blast model. We evaluated mPFC, hippocampus CA1, and primary somatosensory/visual cortical areas (S1/V1). Although mTBI did not alter the power of oscillations, it did cause increased coherence of θ (4-10 Hz) and β (10-30 Hz) oscillations within mPFC and S1/V1, reduced CA1 sharp-wave ripple (SWR)-evoked LFP activity in mPFC, downshifted SWR frequencies in CA1, and enhanced θ-γ phase-amplitude coupling (PAC) within mPFC. These abnormalities might be linked to the impaired memory, depression, and persevering fear seen after mTBI. Treatment with the cannabinoid type-2 (CB2) receptor inverse agonist SMM-189 has been shown to mitigate functional deficits and neuronal injury after mTBI in mice. We found that SMM-189 also reversed most of the observed neurophysiological abnormalities. This neurophysiological rescue is likely to stem from the previously reported reduction in neuron loss and/or the preservation of neuronal function and connectivity resulting from SMM-189 treatment, which appears to stem from the biasing of microglia from the proinflammatory M1 state to the prohealing M2 state by SMM-189.

  9. Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage

    International Nuclear Information System (INIS)

    Shiga, Tohru; Matsuyama, Tetsuaki; Kageyama, Hiroyuki; Kohno, Tomoya; Tamaki, Nagara; Ikoma, Katsunori; Isoyama, Hirotaka; Katoh, Chietsugu; Kuge, Yuji; Terae, Satoshi

    2006-01-01

    Traumatic brain injury (TBI) causes brain dysfunction in many patients. However, some patients have severe brain dysfunction but display no abnormalities on magnetic resonance imaging (MRI). There have been some reports of hypometabolism even in such patients. The purpose of this study was to investigate the relationship between metabolic abnormality and loss of neuronal integrity in TBI patients with some symptoms but without MRI abnormalities. The study population comprised ten patients with TBI and ten normal volunteers. All of the patients were examined at least 1 year after the injury. 15 O-labelled gas PET and [ 11 C]flumazenil (FMZ) positron emission tomography (PET) were carried out. The cerebral metabolic rate of oxygen (CMRO 2 ) and binding potential (BP) images of FMZ were calculated. Axial T2WI, T2*WI and FLAIR images were obtained. Coronal images were added in some cases. All of the patients had normal MRI findings, and all showed areas with abnormally low CMRO 2 . Low uptake on BP images was observed in six patients (60%). No lesions that showed low uptake on BP images were without low CMRO 2 . On the other hand, there were 14 lesions with low CMRO 2 but without BP abnormalities. These results indicate that there are metabolic abnormalities in TBI patients with some symptoms after brain injury but without abnormalities on MRI. Some of the hypometabolic lesions showed low BP, indicating a loss of neuronal integrity. Thus, FMZ PET may have potential to distinguish hypometabolism caused by neuronal loss from that caused by other factors. (orig.)

  10. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    Science.gov (United States)

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  11. Schizophrenia and Category-Selectivity in the Brain: Normal for Faces but Abnormal for Houses

    Directory of Open Access Journals (Sweden)

    Lisa Kronbichler

    2018-02-01

    Full Text Available Face processing is regularly found to be impaired in schizophrenia (SZ, thus suggesting that social malfunctioning might be caused by dysfunctional face processing. Most studies focused on emotional face processes, whereas non-emotional face processing received less attention. While current reports on abnormal face processing in SZ are mixed, examinations of non-emotional face processing compared to adequate control stimuli may clarify whether SZ is characterized by a face-processing deficit. Patients with SZ (n = 28 and healthy controls (n = 30 engaged in an fMRI scan where images of non-emotional faces and houses were presented. A simple inverted-picture detection task warranted the participants’ attention. Region of interest (ROI analyses were conducted on face-sensitive regions including the fusiform face area, the occipital face area, and the superior temporal sulcus. Scene-sensitivity was assessed in the parahippocampal place area (PPA and served as control condition. Patients did not show aberrant face-related neural processes in face-sensitive regions. This finding was also evident when analyses were done on individually defined ROIs or on in-house-localizer ROIs. Patients revealed a decreased specificity toward house stimuli as reflected in decreased neural response toward houses in the PPA. Again, this result was supported by supplementary analyses. Neural activation toward neutral faces was not found to be impaired in SZ, therefore speaking against an overall face-processing deficit. Aberrant activation in scene-sensitive PPA is also found in assessments of memory processes in SZ. It is up to future studies to show how impairments in PPA relate to functional outcome in SZ.

  12. Functional brain imaging of episodic memory decline in ageing.

    Science.gov (United States)

    Nyberg, L

    2017-01-01

    The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  13. Impairment of paravascular clearance pathways in the aging brain.

    Science.gov (United States)

    Kress, Benjamin T; Iliff, Jeffrey J; Xia, Maosheng; Wang, Minghuan; Wei, Helen S; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason A; Plog, Benjamin A; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

    2014-12-01

    In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. © 2014 American Neurological Association.

  14. NREM sleep oscillations and brain plasticity in aging

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    Stuart eFogel

    2012-12-01

    Full Text Available The human electroencephalogram (EEG during non-rapid eye movement sleep (NREM is characterized mainly by high-amplitude (> 75 µV, slow-frequency (< 4 Hz waves (slow waves; SW and sleep spindles (~11-15 Hz; > 0.25 s. These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional impact of age-related changes on NREM sleep oscillations. We propose that age-related reduction in sleep-dependent memory consolidation may be due in part to changes in NREM sleep oscillations.

  15. Cyclin A2 promotes DNA repair in the brain during both development and aging.

    Science.gov (United States)

    Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

    2016-07-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.

  16. The role of abnormalities in the corpus callosum in social cognition deficits after Traumatic Brain Injury.

    Science.gov (United States)

    McDonald, Skye; Rushby, Jacqueline A; Dalton, Katie I; Allen, Samantha K; Parks, Nicklas

    2018-08-01

    The corpus callosum (CC) is vulnerable to severe traumatic brain injury (TBI). Social cognition requires integration of non-verbal and verbal information in order to understand social behaviour and may be compromised if the CC is damaged. 17 adults with severe, chronic TBI and 17 control participants underwent structural MRI and Diffusion Tensor Imaging. A region of interest analysis examined fractional anisotropy (FA) and mean diffusivity (MD) across regions of the CC. Performance on The Awareness of Social Inference Test (TASIT): part 1 (emotion recognition) and parts 2 and 3 (social inference), was examined in relation to FA and MD. Across participants, higher genu FA values were related to higher TASIT part 3 scores. Increased splenium FA was associated with better performance for TASIT parts 1-3. There was no association between DTI values and TASIT in the controls alone. In the TBI group, FA of the genu and splenium was correlated with TASIT part 3. The pattern of performance was similar when controlling for non-social cognitive ability. In conclusion, social information is complex and multi-modal requiring inter-hemispheric connection. People with TBI, regardless of focal grey matter injury, may lose social cognitive ability due to trauma related changes to the corpus callosum.

  17. Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

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    Kaidanovich-Beilin Oksana

    2009-11-01

    Full Text Available Abstract Background Glycogen synthase kinase-3 (GSK-3 is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Results Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells. Conclusion Taken together, these data support a role for the GSK-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders.

  18. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    Science.gov (United States)

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  19. Structural brain abnormalities in a single gene disorder associated with epilepsy, language impairment and intellectual disability

    Directory of Open Access Journals (Sweden)

    Joe Bathelt

    2016-01-01

    Full Text Available Childhood speech and language deficits are highly prevalent and are a common feature of neurodevelopmental disorders. However, it is difficult to investigate the underlying causal pathways because many diagnostic groups have a heterogeneous aetiology. Studying disorders with a shared genetic cause and shared cognitive deficits can provide crucial insight into the cellular mechanisms and neural systems that give rise to those impairments. The current study investigated structural brain differences of individuals with mutations in ZDHHC9, which is associated with a specific neurodevelopmental phenotype including prominent speech and language impairments and intellectual disability. We used multiple structural neuroimaging methods to characterise neuroanatomy in this group, and observed bilateral reductions in cortical thickness in areas surrounding the temporo-parietal junction, parietal lobule, and inferior frontal lobe, and decreased microstructural integrity of cortical, subcortical-cortical, and interhemispheric white matter projections. These findings are compared to reports for other genetic groups and genetically heterogeneous disorders with a similar presentation. Overlap in the neuroanatomical phenotype suggests a common pathway that particularly affects the development of temporo-parietal and inferior frontal areas, and their connections.

  20. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). Copyright © 2013 by the Research Society on Alcoholism.

  1. Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

    Science.gov (United States)

    Bischof, Gérard N; Park, Denise C

    2015-01-01

    This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

  2. Neural Plastic Effects of Cognitive Training on Aging Brain

    Directory of Open Access Journals (Sweden)

    Natalie T. Y. Leung

    2015-01-01

    Full Text Available Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n=109 and the Active Control Group (n=100. Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  3. Neural Plastic Effects of Cognitive Training on Aging Brain.

    Science.gov (United States)

    Leung, Natalie T Y; Tam, Helena M K; Chu, Leung W; Kwok, Timothy C Y; Chan, Felix; Lam, Linda C W; Woo, Jean; Lee, Tatia M C

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  4. Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.

    Science.gov (United States)

    Foscarin, Simona; Raha-Chowdhury, Ruma; Fawcett, James W; Kwok, Jessica C F

    2017-06-28

    Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.

  5. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

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    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  6. Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

    Science.gov (United States)

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-09-01

    Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. Abnormal pain processing in chronic tension-type headache: a high-density EEG brain mapping study

    DEFF Research Database (Denmark)

    Buchgreitz, L.; Egsgaard, L.L.; Jensen, R.

    2008-01-01

    Central sensitization caused by prolonged nociceptive input from muscles is considered to play an important role for chronification of tension-type headache. In the present study we used a new high-density EEG brain mapping technique to investigate spatiotemporal aspects of brain activity...... in response to muscle pain in 19 patients with chronic tension-type headache (CTTH) and 19 healthy, age- and sex-matched controls. Intramuscular electrical stimuli (single and train of five pulses delivered at 2 Hz) were applied to the trapezius muscle and somatosensory evoked potentials were recorded...... with 128-channel EEG both in- and outside a condition with induced tonic neck/shoulder muscle pain (glutamate injection into the trapezius muscle). Significant reduction in magnitude during and after induced tonic muscle pain was found in controls at the P200 dipole in response to both the first (baseline...

  8. Nutrition in brain development and aging: role of essential fatty acids.

    Science.gov (United States)

    Uauy, Ricardo; Dangour, Alan D

    2006-05-01

    The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

  9. Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample

    Energy Technology Data Exchange (ETDEWEB)

    Tomse, Petra; Jensterle, Luka; Grmek, Marko; Zaletel, Katja [University Medical Centre Ljubljana, Department of Nuclear Medicine, Ljubljana (Slovenia); Pirtosek, Zvezdan; Trost, Maja [University Medical Centre Ljubljana, Department of Neurology, 1000 Ljubljana (Slovenia); Dhawan, Vijay; Peng, Shichun; Eidelberg, David; Ma, Yilong [The Feinstein Institute for Medical Research, Center for Neurosciences, Manhasset, NY (United States)

    2017-05-15

    The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p < 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p < 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression. (orig.)

  10. Extratemporal abnormalities of brain parenchyma in young adults with temporal lobe epilepsy: A diffusion tensor imaging study

    International Nuclear Information System (INIS)

    Yin, X.-Y.; Qiu, S.-J.; Liu, Z.-Y.; Wang, H.-Z.; Xiong, W.-F.; Li, S.-S.; Wang, Y.

    2014-01-01

    Aim: To examine extratemporal abnormalities of the cerebral parenchyma in young adult temporal lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI). Materials and methods: The study comprised 20 adults with unilateral TLE and 20 controls. The fractional anisotropy (FA), apparent diffusion coefficient (ADC), parallel eigenvalue (λ ∥ ), and perpendicular eigenvalue (λ ⊥ ) were calculated in the regions of interest (ROIs) using a 3 T MRI system. ROIs included the anterior/posterior limb of the internal capsule (AIC/PIC), external capsule (EC), head of caudate nucleus (HCN), lenticular nucleus (LN), thalamus (TL), and genu/body/splenium of the corpus callosum (GCC/BCC/SCC). Results: Compared to controls, TLE patients showed lower FA in all ROIs; higher ADC in bilateral ECs, HCNs, TLs, and BCC; lower λ ∥ in the ipsilateral LN and bilateral AICs, TL, and GCC; and higher λ ⊥ in all ROIs except the bilateral PICs. In TLE patients, the ipsilateral TL had decreased FA compared with the contralateral TL. Pearson correlation analysis revealed a negative correlation between the ADC of the GCC and the age at onset of epilepsy; the λ ∥ of the ipsilateral PIC and age at onset of epilepsy; the λ ⊥ of the contralateral AIC and duration of epilepsy, respectively; and a positive correlation between the ADC of the GCC and the duration of epilepsy and the λ ⊥ of the GCC and the duration of epilepsy, respectively. Conclusion: The study revealed bilateral extratemporal abnormalities in young adult TLE patients compared with controls. In addition, TLE patients with younger age at onset or longer duration of epilepsy may have more serious extratemporal changes

  11. Autosomal dominant inheritance of brain cardiolipin fatty acid abnormality in VM/DK mice: association with hypoxic-induced cognitive insensitivity.

    Science.gov (United States)

    Ta, Nathan L; Jia, Xibei; Kiebish, Michael; Seyfried, Thomas N

    2014-01-01

    Cardiolipin is a complex polyglycerol phospholipid found almost exclusively in the inner mitochondrial membrane and regulates numerous enzyme activities especially those related to oxidative phosphorylation and coupled respiration. Abnormalities in cardiolipin can impair mitochondrial function and bioenergetics. We recently demonstrated that the ratio of shorter chain saturated and monounsaturated fatty acids (C16:0; C18:0; C18:1) to longer chain polyunsaturated fatty acids (C18:2; C20:4; C22:6) was significantly greater in the brains of adult VM/DK (VM) inbred mice than in the brains of C57BL/6 J (B6) mice. The cardiolipin fatty acid abnormalities in VM mice are also associated with alterations in the activity of mitochondrial respiratory complexes. In this study we found that the abnormal brain fatty acid ratio in the VM strain was inherited as an autosomal dominant trait in reciprocal B6 × VM F1 hybrids. To evaluate the potential influence of brain cardiolipin fatty acid composition on cognitive sensitivity, we placed the parental B6 and VM mice and their reciprocal male and female B6VMF1 hybrid mice (3-month-old) in a hypoxic chamber (5 % O2). Cognitive awareness (conscientiousness) under hypoxia was significantly lower in the VM parental mice and F1 hybrid mice (11.4 ± 0.4  and 11.0 ± 0.4 min, respectively) than in the parental B6 mice (15.3 ± 1.4 min), indicating an autosomal dominant inheritance like that of the brain cardiolipin abnormalities. These findings suggest that impaired cognitive awareness under hypoxia is associated with abnormalities in neural lipid composition.

  12. Microglial cell dysregulation in Brain Aging and Neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Rommy eVon Bernhardi

    2015-07-01

    Full Text Available Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergo phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD. We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide secretion in microglia from young mice, induction of reactive oxygen species (ROS predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in a reduction of protective activation and a facilitation of cytotoxic activation of microglia, resulting in the

  13. Revisiting nicotine's role in the ageing brain and cognitive impairment

    DEFF Research Database (Denmark)

    Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

    2017-01-01

    stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening...... in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

  14. Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

    Science.gov (United States)

    Hughes, J R; Bowes, S G; Leeman, A L; O'Neill, C J; Deshmukh, A A; Nicholson, P W; Dobbs, S M; Dobbs, R J

    1990-01-01

    1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes were made simultaneously by heel and forefoot, there were no instances of the forefoot preceding the heel. No significant effect of age on an index of normality of foot strikes was detected (P greater than 0.3). 3. The effect on foot strike of substituting placebo for a morning dose of a levodopa/carbidopa combination was studied in a double-blind, cross-over trial in 14 patients, aged 64 to 88 years, with no overt fluctuations in control of their idiopathic Parkinson's disease in relation to dosing. On placebo treatment there was a highly significant (P = 0.004) reduction in the number of more normal strikes, i.e. heel strikes plus simultaneous heel and forefoot strikes. The effect appeared unrelated to the corresponding difference between active and placebo treatments in plasma concentration of levodopa or a metabolite of long half-time, 3-O-methyldopa (3OMD). However, it correlated negatively (P less than 0.05) with the mean of the 3OMD concentrations. 4. It appears that some abnormalities of foot strike due to Parkinson's disease are reversible. Employing test conditions, designed to provoke abnormalities of foot strike, might be useful in screening for pre-clinical Parkinson's disease. PMID:2306409

  15. Does age matter? Age and rehabilitation of visual field disorders after brain injury.

    Science.gov (United States)

    Schuett, Susanne; Zihl, Josef

    2013-04-01

    Homonymous visual field disorders (HVFD) are frequent and disabling consequences of acquired brain injury, particularly in older age. Their rehabilitation is therefore of great importance. Compensatory oculomotor therapy has been found to be effective in improving the associated functional impairments in reading and visual exploration. But older age is commonly considered to adversely affect practice-dependent functional plasticity and, thus, functional and rehabilitation outcome after acquired brain injury. The effect of age in the compensatory treatment of HVFD, however, has never been investigated hitherto. It remains unknown whether age determines not only patients' functional impairments but also the rehabilitation outcome and the required amount of treatment. We therefore present the first study to determine the effect of age in 38 patients with HVFD receiving compensatory oculomotor treatment for their reading and visual exploration impairments. We investigated whether older patients with HVFD (1) show more pronounced impairments and less spontaneous adaptation, (2) show lesser compensatory treatment-related improvement in reading and visual exploration, and (3) require a higher amount of treatment than younger patients. Our main finding is that older patients achieve the same treatment-induced improvements in reading and visual exploration with the same amount of treatment as younger patients; severity of functional impairment also did not differ between older and younger patients, at least in reading. Age does not seem to be a critical