Sample records for abnormal brain enlargement

  1. High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

    PubMed Central

    Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

    2010-01-01

    Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

  2. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders

    PubMed Central

    Nordahl, Christine Wu; Lange, Nicholas; Li, Deana D.; Barnett, Lou Ann; Lee, Aaron; Buonocore, Michael H.; Simon, Tony J.; Rogers, Sally; Ozonoff, Sally; Amaral, David G.

    2011-01-01

    Autism is a heterogeneous disorder with multiple behavioral and biological phenotypes. Accelerated brain growth during early childhood is a well-established biological feature of autism. Onset pattern, i.e., early onset or regressive, is an intensely studied behavioral phenotype of autism. There is currently little known, however, about whether, or how, onset status maps onto the abnormal brain growth. We examined the relationship between total brain volume and onset status in a large sample of 2- to 4-y-old boys and girls with autism spectrum disorder (ASD) [n = 53, no regression (nREG); n = 61, regression (REG)] and a comparison group of age-matched typically developing controls (n = 66). We also examined retrospective head circumference measurements from birth through 18 mo of age. We found that abnormal brain enlargement was most commonly found in boys with regressive autism. Brain size in boys without regression did not differ from controls. Retrospective head circumference measurements indicate that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4–6 mo of age. There were no differences in brain size in girls with autism (n = 22, ASD; n = 24, controls). These results suggest that there may be distinct neural phenotypes associated with different onsets of autism. For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported. Thus, rapid head growth may be a risk factor for regressive autism. PMID:22123952

  3. Disappearance of enlarged nuchal translucency before 14 weeks' gestation: relationship with chromosomal abnormalities and pregnancy outcome.

    PubMed

    Müller, M A; Pajkrt, E; Bleker, O P; Bonsel, G J; Bilardo, C M

    2004-08-01

    The aim of this study was to investigate the natural course of enlarged nuchal translucency (NT) and to determine if its disappearance before 14 weeks' gestation is a favorable prognostic sign in relation to fetal karyotype and pregnancy outcome. A total of 147 women with increased NT (> 95th centile) at first measurement were included in this study. A second measurement was performed in all cases, at an interval of at least 2 days. Both measurements were taken between 10 + 3 and 14 + 0 weeks. All women underwent chorionic villus sampling or amniocentesis for subsequent karyotyping. In those women with a normal karyotype, a fetal anomaly scan was performed at 20 weeks' gestation. Pregnancy outcome was recorded in all cases. The finding of persistent or disappearing NT enlargement was analyzed in relation to fetal karyotype and pregnancy outcome. Of the 147 paired measurements, NT remained enlarged at the second measurement in 121 (82%) cases. An abnormal karyotype was found in 35% of these cases. In 26 (18%) fetuses the NT measurement was found to be below the 95th percentile at the second measurement and in only two of them an abnormal karyotype was found (8%). In the 103 chromosomally normal fetuses an adverse outcome (i.e. fetal loss or structural defects) was recorded in 22 fetuses with persistent enlargement (28%) and in four fetuses with disappearing enlargement (17%). Disappearance of an enlarged NT before 14 weeks' gestation is not a rare phenomenon and seems to be a favorable prognostic sign with respect to fetal karyotype. Overall, no significant difference in pregnancy outcome was found between chromosomally normal fetuses with persisting or disappearing NT enlargement. Copyright 2004 ISUOG

  4. Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum.

    PubMed

    Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

    2017-03-01

    Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates ( N =124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked.

  5. Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum

    PubMed Central

    Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S.; Kiehl, Kent A.; Koenigs, Michael

    2016-01-01

    Background Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. Methods We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates (N=124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Results Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. Conclusion These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked. PMID:28367514

  6. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

    PubMed

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2014-01-01

    Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation

  7. Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities.

    PubMed

    Gauthier, Sébastien A; Pérez-González, Rocío; Sharma, Ajay; Huang, Fang-Ke; Alldred, Melissa J; Pawlik, Monika; Kaur, Gurjinder; Ginsberg, Stephen D; Neubert, Thomas A; Levy, Efrat

    2017-08-29

    A dysfunctional endosomal pathway and abnormally enlarged early endosomes in neurons are an early characteristic of Down syndrome (DS) and Alzheimer's disease (AD). We have hypothesized that endosomal material can be released by endosomal multivesicular bodies (MVBs) into the extracellular space via exosomes to relieve neurons of accumulated endosomal contents when endosomal pathway function is compromised. Supporting this, we found that exosome secretion is enhanced in the brains of DS patients and a mouse model of the disease, and by DS fibroblasts. Furthermore, increased levels of the tetraspanin CD63, a regulator of exosome biogenesis, were observed in DS brains. Importantly, CD63 knockdown diminished exosome release and worsened endosomal pathology in DS fibroblasts. Taken together, these data suggest that increased CD63 expression enhances exosome release as an endogenous mechanism mitigating endosomal abnormalities in DS. Thus, the upregulation of exosome release represents a potential therapeutic goal for neurodegenerative disorders with endosomal pathology.

  8. Brain and bone abnormalities of thanatophoric dwarfism.

    PubMed

    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.

  9. Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

    PubMed Central

    Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

    2016-01-01

    Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo. PMID:27626081

  10. Neuroimaging evidence of brain abnormalities in mastocytosis.

    PubMed

    Boddaert, N; Salvador, A; Chandesris, M O; Lemaître, H; Grévent, D; Gauthier, C; Naggara, O; Georgin-Lavialle, S; Moura, D S; Munsch, F; Jaafari, N; Zilbovicius, M; Lortholary, O; Gaillard, R; Hermine, O

    2017-08-08

    Mastocytosis is a rare disease in which chronic symptoms are related to mast cell accumulation and activation. Patients can display depression-anxiety-like symptoms and cognitive impairment. The pathophysiology of these symptoms may be associated with tissular mast cell infiltration, mast cell mediator release or both. The objective of this study is to perform morphological or functional brain analyses in mastocytosis to identify brain changes associated with this mast cell disorder. We performed a prospective and monocentric comparative study to evaluate the link between subjective psycho-cognitive complaints, psychiatric evaluation and objective medical data using magnetic resonance imaging with morphological and perfusion sequences (arterial spin-labeled perfusion) in 39 patients with mastocytosis compared with 33 healthy controls. In the test cohort of 39 mastocytosis patients with psycho-cognitive complaints, we found that 49% of them had morphological brain abnormalities, mainly abnormal punctuated white matter abnormalities (WMA). WMA were equally frequent in cutaneous mastocytosis patients and indolent forms of systemic mastocytosis patients (42% and 41% of patients with WMA, respectively). Patients with WMA showed increased perfusion in the putamen compared with patients without WMA and with healthy controls. Putamen perfusion was also negatively correlated with depression subscores. This study demonstrates, for we believe the first time, a high prevalence of morphological and functional abnormalities in the brains of mastocytosis patients with neuropsychiatric complaints. Further studies are required to determine the mechanism underpinning this association and to ascertain its specificity.

  11. Brain enlargement and dental reduction were not linked in hominin evolution

    PubMed Central

    Smaers, Jeroen B.; Holloway, Ralph L.

    2017-01-01

    The large brain and small postcanine teeth of modern humans are among our most distinctive features, and trends in their evolution are well studied within the hominin clade. Classic accounts hypothesize that larger brains and smaller teeth coevolved because behavioral changes associated with increased brain size allowed a subsequent dental reduction. However, recent studies have found mismatches between trends in brain enlargement and posterior tooth size reduction in some hominin species. We use a multiple-variance Brownian motion approach in association with evolutionary simulations to measure the tempo and mode of the evolution of endocranial and dental size and shape within the hominin clade. We show that hominin postcanine teeth have evolved at a relatively consistent neutral rate, whereas brain size evolved at comparatively more heterogeneous rates that cannot be explained by a neutral model, with rapid pulses in the branches leading to later Homo species. Brain reorganization shows evidence of elevated rates only much later in hominin evolution, suggesting that fast-evolving traits such as the acquisition of a globular shape may be the result of direct or indirect selection for functional or structural traits typical of modern humans. PMID:28049819

  12. Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users

    PubMed Central

    Kaufman, Marc J.; Janes, Amy C.; Hudson, James I.; Brennan, Brian P.; Kanayama, Gen; Kerrigan, Andrew R.; Jensen, J. Eric; Pope, Harrison G.

    2015-01-01

    Background Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. Methods This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). Results AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Conclusions Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction. PMID:25986964

  13. Prenatal isolated mild ventriculomegaly is associated with persistent ventricle enlargement at ages 1 and 2.

    PubMed

    Lyall, Amanda E; Woolson, Sandra; Wolfe, Honor M; Goldman, Barbara Davis; Reznick, J Steven; Hamer, Robert M; Lin, Weili; Styner, Martin; Gerig, Guido; Gilmore, John H

    2012-08-01

    Enlargement of the lateral ventricles is thought to originate from abnormal prenatal brain development and is associated with neurodevelopmental disorders. Fetal isolated mild ventriculomegaly (MVM) is associated with the enlargement of lateral ventricle volumes in the neonatal period and developmental delays in early childhood. However, little is known about postnatal brain development in these children. Twenty-eight children with fetal isolated MVM and 56 matched controls were followed at ages 1 and 2 years with structural imaging on a 3T Siemens scanner and assessment of cognitive development with the Mullen Scales of Early Learning. Lateral ventricle, total gray and white matter volumes, and Mullen cognitive composite scores and subscale scores were compared between groups. Compared to controls, children with prenatal isolated MVM had significantly larger lateral ventricle volumes at ages 1 and 2 years. Lateral ventricle volume at 1 and 2 years of age was significantly correlated with prenatal ventricle size. Enlargement of the lateral ventricles was associated with increased intracranial volumes and increased gray and white matter volumes. Children with MVM had Mullen composite scores similar to controls, although there was evidence of delay in fine motor and expressive language skills. Children with prenatal MVM have persistent enlargement of the lateral ventricles through the age of 2 years; this enlargement is associated with increased gray and white matter volumes and some evidence of delay in fine motor and expressive language development. Further study is needed to determine if enlarged lateral ventricles are associated with increased risk for neurodevelopmental disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Morphometric brain abnormalities in boys with conduct disorder.

    PubMed

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

    2008-05-01

    Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

  15. Prevalence of prenatal brain abnormalities in fetuses with congenital heart disease: a systematic review.

    PubMed

    Khalil, A; Bennet, S; Thilaganathan, B; Paladini, D; Griffiths, P; Carvalho, J S

    2016-09-01

    Studies have shown an association between congenital heart defects (CHDs) and postnatal brain abnormalities and neurodevelopmental delay. Recent evidence suggests that some of these brain abnormalities are present before birth. The primary aim of this study was to perform a systematic review to quantify the prevalence of prenatal brain abnormalities in fetuses with CHDs. MEDLINE, EMBASE and The Cochrane Library were searched electronically. Reference lists within each article were hand-searched for additional reports. The outcomes observed included structural brain abnormalities (on magnetic resonance imaging (MRI)) and changes in brain volume (on MRI, three-dimensional (3D) volumetric MRI, 3D ultrasound and phase-contrast MRI), brain metabolism or maturation (on magnetic resonance spectroscopy and phase-contrast MRI) and brain blood flow (on Doppler ultrasound, phase-contrast MRI and 3D power Doppler ultrasound) in fetuses with CHDs. Cohort and case-control studies were included and cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Proportion meta-analysis was used for analysis. Between-study heterogeneity was assessed using the I(2) test. The search yielded 1943 citations, and 20 studies (n = 1175 cases) were included in the review. Three studies reported data on structural brain abnormalities, while data on altered brain volume, metabolism and blood flow were reported in seven, three and 14 studies, respectively. The three studies (221 cases) reporting on structural brain abnormalities were suitable for inclusion in a meta-analysis. The prevalence of prenatal structural brain abnormalities in fetuses with CHD was 28% (95% CI, 18-40%), with a similar prevalence (25% (95% CI, 14-39%)) when tetralogy of Fallot was considered alone. These abnormalities included ventriculomegaly (most common), agenesis of the corpus callosum, ventricular bleeding, increased extra-axial space, vermian hypoplasia, white

  16. Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

    PubMed

    Jiang, Ze Dong

    2013-08-01

    Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

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

    PubMed

    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.

  18. Bilateral parotid gland enlargement and palpable nephromegaly in infant acute lymphoblastic leukemia: case report and review of the literature.

    PubMed

    Saha, Aniket; Dandekar, Smita; Milla, Sarah; Roman, Elizabeth; Bhatla, Teena

    2014-04-01

    Acute lymphoblastic leukemia (ALL) in infants below 1 year of age accounts for 2.5% to 5% of childhood ALL. Most children with ALL present with fever, bruising, mucosal bleeding, bone pain, pallor, hepatosplenomegaly, and lymphadenopathy. Common sites of extramedullary involvement at diagnosis include liver, spleen, lymph nodes, brain, and testes. Nephromegaly has also been reported. We present a novel case of bilateral parotid enlargement along with bilateral palpable nephromegaly in a patient with newly diagnosed infant ALL. This unique presentation highlights the importance of considering ALL in the differential diagnosis of parotid enlargement especially when associated with abnormal blood counts.

  19. Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

    PubMed Central

    Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

    2014-01-01

    Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

  20. Brain growth rate abnormalities visualized in adolescents with autism.

    PubMed

    Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

    2013-02-01

    Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

  1. Abnormal electroretinogram associated with developmental brain anomalies.

    PubMed Central

    Cibis, G W; Fitzgerald, K M

    1995-01-01

    PURPOSE: We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain anomalies include cortical dysgenesis, lissencephaly, porencephaly, cerebellar and corpus callosum hypoplasia. We describe six exemplar cases. METHODS: Scotopic and photopic ERGs adherent to international standards were performed as well as photopic ERGs to long-duration stimuli. CT or MRI studies were also done. The ERGs were compared to age-matched normal control subjects. RESULTS: ERG changes include reduced amplitude b-waves to blue and red stimuli under scotopic testing conditions. Implicit times were often delayed. The photopic responses also showed reduced amplitude a- and b-waves with implicit time delays. The long-duration photopic ERG done in one case shows attenuation of both ON- and OFF-responses. CONCLUSIONS: Common underlying developmental genetic or environmental unifying casualties are speculated to be at fault in causing these cases of associated retinal and brain abnormalities. No single etiology is expected. Multiple potential causes acting early in embryogenesis effecting neuronal induction, migration and differentiation are theorized. These occur at a time when brain and retinal cells are sufficiently undifferentiated to be similarly effected. We call these cases examples of Brain Retina Neuroembryodysgenesis (BRNED). Homeobox and PAX genes with global neuronal developmental influences are gene candidates to unify the observed disruption of brain and retinal cell development. The ERG can provide a valuable clinical addition in understanding and ultimately classifying these disorders. Images FIGURE 1 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 PMID:8719676

  2. Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

    PubMed

    Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

    2013-02-22

    Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

  3. Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain

    PubMed Central

    Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

    2013-01-01

    Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement. PMID:23256194

  4. Computer-Aided Diagnosis of Splenic Enlargement Using Wave Pattern of Spleen in Abdominal CT Images: Initial Observations

    NASA Astrophysics Data System (ADS)

    Seong, Won; Cho, June-Sik; Noh, Seung-Moo; Park, Jong-Won

    In general, the spleen accompanied by abnormal abdomen is hypertrophied. However, if the spleen size is originally small, it is hard to detect the splenic enlargement due to abnormal abdomen by simply measure the size. On the contrary, the spleen size of a person having a normal abdomen may be large by nature. Therefore, measuring the size of spleen is not a reliable diagnostic measure of its enlargement or the abdomen abnormality. This paper proposes an automatic method to diagnose the splenic enlargement due to abnormality, by examining the boundary pattern of spleen in abdominal CT images.

  5. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

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

    PubMed

    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) versus those imaged delayed (>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

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

    PubMed

    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.

  8. Postural abnormalities and contraversive pushing following right hemisphere brain damage.

    PubMed

    Lafosse, C; Kerckhofs, E; Vereeck, L; Troch, M; Van Hoydonck, G; Moeremans, M; Sneyers, C; Broeckx, J; Dereymaeker, L

    2007-06-01

    We investigated the presence of postural abnormalities in a consecutive sample of stroke patients, with either left or right brain damage, in relation to their perceived body position in space. The presence or absence of posture-related symptoms was judged by two trained therapists and subsequently analysed by hierarchical classes analysis (HICLAS). The subject classes resulting from the HICLAS model were further validated with respect to posture-related measurements, such as centre of gravity position and head position, as well as measurements related to the postural body scheme, such as the perception of postural and visual verticality. The results of the classification analysis clearly demonstrated a relation between the presence of right brain damage and abnormalities in body geometry. The HICLAS model revealed three classes of subjects: The first class contained almost all the patients without neglect and without any signs of contraversive pushing. They were mainly characterised by a normal body axis in any position. The second class were all neglect patients but predominantly without any contraversive pushing. The third class contained right brain damaged patients, all showing neglect and mostly exhibiting contraversive pushing. The patients in the third class showed a clear resistance to bringing the weight over to the ipsilesional side when the therapist attempted to make the subject achieve a vertical posture across the midline. The clear correspondence between abnormalities of the observed body geometry and the tilt of the subjective postural and visual vertical suggests that a patient's postural body geometry is characterised by leaning towards the side of space where he/she feels aligned with an altered postural body scheme. The presence of contraversive pushing after right brain damage points in to a spatial higher-order processing deficit underlying the higher frequency and severity of the axial postural abnormalities found after right brain lesions.

  9. Sodium valproate induced gingival enlargement with pre-existing chronic periodontitis.

    PubMed

    Joshipura, Vaibhavi

    2012-04-01

    Gingival enlargement is a common clinical feature of gingival and periodontal diseases. Currently, more than 20 prescription medications are associated with gingival enlargement. Although the mechanisms of action may be different, the clinical and microscopic appearance of drug-induced gingival enlargement is similar with any drug. Gingival enlargement produces esthetic changes, and clinical symptoms including pain, tenderness, bleeding, speech disturbances, abnormal tooth movement, dental occlusion problems, enhancement of caries development and periodontal disorders. Sodium valproate is considered to produce gingival enlargement, but very rarely. This case report features sodium valproate induced gingival enlargement in a patient with pre-existing chronic periodontitis, who came to the Dental Department, Chinmaya Mission Hospital, Bangalore. The case is special as the patient did not develop the enlargement in spite of taking phenytoin for 1 year and developed enlargement with sodium valproate within 6 months.

  10. Mid-gestation brain Doppler and head biometry in fetuses with congenital heart disease predict abnormal brain development at birth.

    PubMed

    Masoller, N; Sanz-CortéS, M; Crispi, F; Gómez, O; Bennasar, M; Egaña-Ugrinovic, G; Bargalló, N; Martínez, J M; Gratacós, E

    2016-01-01

    Fetuses with congenital heart disease (CHD) show evidence of abnormal brain development before birth, which is thought to contribute to adverse neurodevelopment during childhood. Our aim was to evaluate whether brain development in late pregnancy can be predicted by fetal brain Doppler, head biometry and the clinical form of CHD at the time of diagnosis. This was a prospective cohort study including 58 fetuses with CHD, diagnosed at 20-24 weeks' gestation, and 58 normal control fetuses. At the time of diagnosis, we recorded fetal head circumference (HC), biparietal diameter, middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and brain perfusion by fractional moving blood volume. We classified cases into one of two clinical types defined by the expected levels (high or low) of placental (well-oxygenated) blood perfusion, according to the anatomical defect. All fetuses underwent subsequent 3T-magnetic resonance imaging (MRI) at 36-38 weeks' gestation. Abnormal prenatal brain development was defined by a composite score including any of the following findings on MRI: total brain volume <  10(th) centile, parietoccipital or cingulate fissure depth <  10(th) centile or abnormal metabolic profile in the frontal lobe. Logistic regression analysis demonstrated that MCA-PI (odds ratio (OR), 12.7; P = 0.01), CPR (OR, 8.7; P = 0.02) and HC (OR, 6.2; P = 0.02) were independent predictors of abnormal neurodevelopment; however, the clinical type of CHD was not. Fetal brain Doppler and head biometry at the time of CHD diagnosis are independent predictors of abnormal brain development at birth, and could be used in future algorithms to improve counseling and targeted interventions. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

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

    PubMed

    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%.

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

    PubMed

    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 < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were 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.

  13. Volume estimation of brain abnormalities in MRI data

    NASA Astrophysics Data System (ADS)

    Suprijadi, Pratama, S. H.; Haryanto, F.

    2014-02-01

    The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

  14. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    ERIC Educational Resources Information Center

    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…

  15. An unusual case of generalized severe gingival enlargement during pregnancy.

    PubMed

    McIntosh, Crystal L; Kolhatkar, Shilpa; Winkler, James R; Ojha, Junu; Bhola, Monish

    2010-01-01

    Increased hormone levels that are present during puberty and pregnancy are associated with localized or generalized gingival enlargement. This article reviews the gingival alterations that can occur during pregnancy and describes a case of generalized severe gingival enlargement associated with pregnancy and its management. A 36-year-old woman had severe bilateral gingival enlargement of short duration. The patient denied taking any medications. The laboratory report revealed no systemic abnormalities; however, the report disclosed that she was pregnant. Surgical therapy for the gingival enlargement included gingivectomy and gingivoplasty of all quadrants, which reduced the size of the enlarged gingiva. Postoperative visits demonstrated uneventful healing, with no recurrence seen at the one-year follow-up appointment. It appears that the English literature includes only one other case report that discusses generalized gingival enlargement during pregnancy. Pregnancy-related gingival enlargement should be included as a differential diagnosis in women who have non-drug-induced generalized gingival enlargement.

  16. Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

    PubMed

    Brossard-Racine, M; du Plessis, A J; Vezina, G; Robertson, R; Bulas, D; Evangelou, I E; Donofrio, M; Freeman, D; Limperopoulos, C

    2014-08-01

    Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study. © 2014 by American Journal of Neuroradiology.

  17. 42 CFR 37.53 - Notification of abnormal roentgenographic findings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer... findings suggesting, abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other...

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

    PubMed

    Moran, Marcel E; Hulshoff Pol, Hilleke; Gogtay, Nitin

    2013-11-01

    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.

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

    PubMed Central

    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

  20. Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

    PubMed

    Horga, Guillermo; Bernacer, Javier; Dusi, Nicola; Entis, Jonathan; Chu, Kingwai; Hazlett, Erin A; Haznedar, M Mehmet; Kemether, Eileen; Byne, William; Buchsbaum, Monte S

    2011-10-01

    Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed

    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.

  4. Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients.

    PubMed

    Guo, Wenbin; Song, Yan; Liu, Feng; Zhang, Zhikun; Zhang, Jian; Yu, Miaoyu; Liu, Jianrong; Xiao, Changqing; Liu, Guiying; Zhao, Jingping

    2015-05-01

    Schizophrenia patients and their unaffected siblings share similar brain functional and structural abnormalities. However, no study is engaged to investigate whether and how functional abnormalities are related to structural abnormalities in unaffected siblings. This study was undertaken to examine the association between functional and anatomical abnormalities in unaffected siblings. Forty-six unaffected siblings of schizophrenia patients and 46 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. Voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were utilized to analyze imaging data. The VBM analysis showed gray matter volume decreases in the fronto-temporal regions (the left middle temporal gyrus and right inferior frontal gyrus, orbital part) and increases in basal ganglia system (the left putamen). Functional abnormalities measured by ALFF and fALFF mainly involved in the fronto-limbic-sensorimotor circuit (decreased ALFF in bilateral middle frontal gyrus and the right middle cingulate gyrus, and decreased fALFF in the right inferior frontal gyrus, orbital part; and increased ALFF in the left fusiform gyrus and left lingual gyrus, and increased fALFF in bilateral calcarine cortex). No significant correlation was found between functional and anatomical abnormalities in the sibling group. A dissociation pattern of brain regions with functional and anatomical abnormalities is observed in unaffected siblings. Our findings suggest that brain functional and anatomical abnormalities might be present independently in unaffected siblings of schizophrenia patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

    A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

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

    PubMed

    Morgan, K D; Dazzan, P; Morgan, C; Lappin, J; Hutchinson, G; Chitnis, X; Suckling, J; Fearon, P; Jones, P B; Leff, J; Murray, R M

    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. We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls. White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus. We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.

  7. Abnormal brain development in newborns with congenital heart disease.

    PubMed

    Miller, Steven P; McQuillen, Patrick S; Hamrick, Shannon; Xu, Duan; Glidden, David V; Charlton, Natalie; Karl, Tom; Azakie, Anthony; Ferriero, Donna M; Barkovich, A James; Vigneron, Daniel B

    2007-11-08

    Congenital heart disease in newborns is associated with global impairment in development. We characterized brain metabolism and microstructure, as measures of brain maturation, in newborns with congenital heart disease before they underwent heart surgery. We studied 41 term newborns with congenital heart disease--29 who had transposition of the great arteries and 12 who had single-ventricle physiology--with the use of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before cardiac surgery. We calculated the ratio of N-acetylaspartate to choline (which increases with brain maturation), the ratio of lactate to choline (which decreases with maturation), average diffusivity (which decreases with maturation), and fractional anisotropy of white-matter tracts (which increases with maturation). We compared these findings with those in 16 control newborns of a similar gestational age. As compared with control newborns, those with congenital heart disease had a decrease of 10% in the ratio of N-acetylaspartate to choline (P=0.003), an increase of 28% in the ratio of lactate to choline (P=0.08), an increase of 4% in average diffusivity (P<0.001), and a decrease of 12% in white-matter fractional anisotropy (P<0.001). Preoperative brain injury, as seen on MRI, was not significantly associated with findings on MRS or DTI. White-matter injury was observed in 13 newborns with congenital heart disease (32%) and in no control newborns. Term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery. The imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero. Copyright 2007 Massachusetts Medical Society.

  8. Infantile Autism and Computerized Tomography Brain-Scan Findings: Specific versus Nonspecific Abnormalities.

    ERIC Educational Resources Information Center

    Balottin, Umberto; And Others

    1989-01-01

    The study of computerized tomography brain-scan findings with 45 autistic and 19 control subjects concluded that autism is nonspecifically associated with brain-scan abnormalities, and that other nonorganic, as well as organic, factors should be taken into account. (Author/DB)

  9. Asymmetric Meckel Cave Enlargement: A Potential Marker of PHACES Syndrome.

    PubMed

    Wright, J N; Wycoco, V

    2017-06-01

    PHACES syndrome is a complex of morphologic abnormalities of unknown cause and includes posterior fossa abnormalities; head and neck infantile hemangiomas; arterial, cardiac, and eye anomalies; and sternal or abdominal wall defects. Accurate identification of the syndrome is important for optimal treatment. The purpose of this study was to investigate the incidence of asymmetric Meckel cave enlargement, a potential novel imaging marker, in a population of patients referred for evaluation of possible PHACES syndrome. Eighty-five patients referred for neuroimaging evaluation of possible PHACES syndrome were identified and stratified on the basis of their ultimate clinical PHACES diagnosis categorization into PHACES, possible PHACES, or not PHACES. MR imaging studies were subsequently reviewed for the presence or absence of unilateral Meckel cave enlargement, with the reviewer blinded to the ultimate PHACES syndrome categorization. Twenty-five of 85 patients (29%) were ultimately categorized as having PHACES or possible PHACES according to consensus guidelines. Asymmetric Meckel cave enlargement was present in 76% (19/25) of these patients and in 82% (19/23) of only those patients with definite PHACES. This finding was present in none of the 60 patients determined not to have PHACES syndrome. In 7/19 patients (37%) with this finding, subtle MR imaging abnormalities consistent with PHACES were missed on the initial MR imaging interpretation. Asymmetric Meckel cave enlargement was a common feature of patients with PHACES in our cohort and may serve as a novel imaging marker. Increased awareness of this imaging feature has the potential to increase the diagnostic accuracy of PHACES. © 2017 by American Journal of Neuroradiology.

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

    PubMed Central

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

    2015-01-01

    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 multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

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

    PubMed

    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.

  12. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  13. Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder.

    PubMed

    Barkataki, Ian; Kumari, Veena; Das, Mrigendra; Taylor, Pamela; Sharma, Tonmoy

    2006-05-15

    Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.

  14. N-terminal pro–brain natriuretic peptide and abnormal brain aging

    PubMed Central

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

    2015-01-01

    Objective: 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. Methods: 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. Results: In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) 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 < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Conclusions: 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. PMID:26231259

  15. Microstructural Abnormalities Were Found in Brain Gray Matter from Patients with Chronic Myofascial Pain

    PubMed Central

    Xie, Peng; Qin, Bangyong; Song, Ganjun; Zhang, Yi; Cao, Song; Yu, Jin; Wu, Jianjiang; Wang, Jiang; Zhang, Tijiang; Zhang, Xiaoming; Yu, Tian; Zheng, Hong

    2016-01-01

    Myofascial pain, presented as myofascial trigger points (MTrPs)-related pain, is a common, chronic disease involving skeletal muscle, but its underlying mechanisms have been poorly understood. Previous studies have revealed that chronic pain can induce microstructural abnormalities in the cerebral gray matter. However, it remains unclear whether the brain gray matters of patients with chronic MTrPs-related pain undergo alteration. In this study, we employed the Diffusion Kurtosis Imaging (DKI) technique, which is particularly sensitive to brain microstructural perturbation, to monitor the MTrPs-related microstructural alterations in brain gray matter of patients with chronic pain. Our results revealed that, in comparison with the healthy controls, patients with chronic myofascial pain exhibited microstructural abnormalities in the cerebral gray matter and these lesions were mainly distributed in the limbic system and the brain areas involved in the pain matrix. In addition, we showed that microstructural abnormalities in the right anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) had a significant negative correlation with the course of disease and pain intensity. The results of this study demonstrated for the first time that there are microstructural abnormalities in the brain gray matter of patients with MTrPs-related chronic pain. Our findings may provide new insights into the future development of appropriate therapeutic strategies to this disease. PMID:28066193

  16. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism.

    PubMed

    Purcell, A E; Jeon, O H; Zimmerman, A W; Blue, M E; Pevsner, J

    2001-11-13

    Studies examining the brains of individuals with autism have identified anatomic and pathologic changes in regions such as the cerebellum and hippocampus. Little, if anything, is known, however, about the molecules that are involved in the pathogenesis of this disorder. To identify genes with abnormal expression levels in the cerebella of subjects with autism. Brain samples from a total of 10 individuals with autism and 23 matched controls were collected, mainly from the cerebellum. Two cDNA microarray technologies were used to identify genes that were significantly up- or downregulated in autism. The abnormal mRNA or protein levels of several genes identified by microarray analysis were investigated using PCR with reverse transcription and Western blotting. alpha-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)- and NMDA-type glutamate receptor densities were examined with receptor autoradiography in the cerebellum, caudate-putamen, and prefrontal cortex. The mRNA levels of several genes were significantly increased in autism, including excitatory amino acid transporter 1 and glutamate receptor AMPA 1, two members of the glutamate system. Abnormalities in the protein or mRNA levels of several additional molecules in the glutamate system were identified on further analysis, including glutamate receptor binding proteins. AMPA-type glutamate receptor density was decreased in the cerebellum of individuals with autism (p < 0.05). Subjects with autism may have specific abnormalities in the AMPA-type glutamate receptors and glutamate transporters in the cerebellum. These abnormalities may be directly involved in the pathogenesis of the disorder.

  17. Prenatal diagnosis of brain abnormalities in Wolf-Hirschhorn (4p-) syndrome.

    PubMed

    De Keersmaecker, B; Albert, M; Hillion, Y; Ville, Y

    2002-05-01

    Although there have been occasional reports of prenatal diagnosis of this syndrome, most cases are diagnosed postnatally. The objective was to evaluate the presence of brain abnormalities in the prenatal diagnosis of Wolf-Hirschhorn syndrome. Prenatal ultrasound and MRI examination of the fetal brain were performed in a case of Wolf-Hirschhorn syndrome. A comprehensive review of Wolf-Hirschhorn syndrome reported between 1960 and 2000 in the literature was carried out. The late diagnosis of a growth-retarded fetus with normal amniotic fluid volume, normal Doppler and negative infection screen calls for a detailed examination of the fetal brain and heart. Multifocal white matter lesions and periventricular cystic changes, which are often attributed to perinatal distress, are possible prenatal features causing suspicion of 4p- syndrome in an IUGR fetus. Subtle abnormalities on ultrasound may suggest a chromosomal problem. Standard cytogenetics cannot always demonstrate a microdeletion. High-resolution banding and molecular analysis can help to confirm the diagnosis. Copyright 2002 John Wiley & Sons, Ltd.

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

    PubMed

    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 (P<0.05). Correlation analysis between feature importance and the statistical significance of metrics was investigated, and the results revealed a strong positive correlation between them. Overall, the current study demonstrated that major depressive disorder is associated with abnormal functional brain network topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms.

  19. Isolated cortical visual loss with subtle brain MRI abnormalities in a case of hypoxic-ischemic encephalopathy.

    PubMed

    Margolin, Edward; Gujar, Sachin K; Trobe, Jonathan D

    2007-12-01

    A 16-year-old boy who was briefly asystolic and hypotensive after a motor vehicle accident complained of abnormal vision after recovering consciousness. Visual acuity was normal, but visual fields were severely constricted without clear hemianopic features. The ophthalmic examination was otherwise normal. Brain MRI performed 11 days after the accident showed no pertinent abnormalities. At 6 months after the event, brain MRI demonstrated brain volume loss in the primary visual cortex and no other abnormalities. One year later, visual fields remained severely constricted; neurologic examination, including formal neuropsychometric testing, was normal. This case emphasizes the fact that hypoxic-ischemic encephalopathy (HIE) may cause enduring damage limited to primary visual cortex and that the MRI abnormalities may be subtle. These phenomena should be recognized in the management of patients with HIE.

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

    PubMed

    Janusonis, Skirmantas

    2005-07-19

    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. 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. 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 experimental studies.

  1. 42 CFR 37.53 - Notification of abnormal roentgenographic findings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer...

  2. 42 CFR 37.53 - Notification of abnormal roentgenographic findings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer...

  3. Solitary tuberculous brain lesions: 24 new cases and a review of the literature.

    PubMed

    Psimaras, D; Bonnet, C; Heinzmann, A; Cárdenas, G; Hernández José Luis, S; Tungaria, A; Behari, S; Lacrois, D; Mokhtari, K; Karantoni, E; Sokrab Tag, E; Idris Mohamed, N; Sönmez, G; Caumes, E; Roze, E

    2014-01-01

    A solitary tuberculous brain lesion (STBL) can be difficult to distinguish from a glioma, metastasis or other infectious disease, especially from a pyogenic brain abscess. We analyzed the clinical characteristics, diagnostic procedures and outcomes of 24 patients with STBL diagnosed in three centers from France, India and Mexico. We also reviewed 92 STBL cases previously reported in the literature. General symptoms were found in 54% of our patients, including enlarged lymph nodes in 20%. Cerebrospinal fluid was typically abnormal, with lymphocytic pleocytosis and a high protein level. The lung CT scan was abnormal in 56% of patients, showing lymphadenopathy or pachipleuritis. Brain MRI or CT was always abnormal, showing contrast-enhanced lesions. Typically, MRI abnormalities were hypointense on T1-weighted sequences, while T2-weighted sequences showed both a peripheral hypersignal and a central hyposignal. The diagnosis was documented microbiologically or supported histologically in 71% of cases. Clinical outcome was good in 83% of cases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis.

    PubMed

    Khalil, A; Suff, N; Thilaganathan, B; Hurrell, A; Cooper, D; Carvalho, J S

    2014-01-01

    Studies have demonstrated an association between congenital heart disease (CHD) and neurodevelopmental delay. Neuroimaging studies have also demonstrated a high incidence of preoperative brain abnormalities. The aim of this study was to perform a systematic review to quantify the non-surgical risk of brain abnormalities and of neurodevelopmental delay in infants with CHD. MEDLINE, EMBASE and The Cochrane Library were searched electronically without language restrictions, utilizing combinations of the terms congenital heart, cardiac, neurologic, neurodevelopment, magnetic resonance imaging, ultrasound, neuroimaging, autopsy, preoperative and outcome. Reference lists of relevant articles and reviews were hand-searched for additional reports. Cohort and case-control studies were included. Studies reporting neurodevelopmental outcomes and/or brain lesions on neuroimaging in infants with CHD before heart surgery were included. Cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Between-study heterogeneity was assessed using the I(2) test. The search yielded 9129 citations. Full text was retrieved for 119 and the following were included in the review: 13 studies (n = 425 cases) reporting on brain abnormalities either preoperatively or in those who did not undergo congenital cardiac surgery and nine (n = 512 cases) reporting preoperative data on neurodevelopmental assessment. The prevalence of brain lesions on neuroimaging was 34% (95% CI, 24-46; I(2) = 0%) in transposition of the great arteries, 49% (95% CI, 25-72; I(2) = 65%) in left-sided heart lesions and 46% (95% CI, 40-52; I(2) =18.1%) in mixed/unspecified cardiac lesions, while the prevalence of neurodevelopmental delay was 42% (95% CI, 34-51; I(2) = 68.9). In the absence of chromosomal or genetic abnormalities, infants with CHD are at increased risk of brain lesions as revealed by neuroimaging and of neurodevelopmental delay. These findings are independent of the surgical risk

  5. Developmental basis for telencephalon expansion in waterfowl: enlargement prior to neurogenesis

    PubMed Central

    Charvet, Christine J.; Striedter, Georg F.

    2009-01-01

    Some altricial and some precocial species of birds have evolved enlarged telencephalons compared with other birds. Previous work has shown that finches and parakeets, two species that hatch in an immature (i.e. altricial) state, enlarged their telencephalon by delaying telencephalic neurogenesis. To determine whether species that hatch in a relatively mature (i.e. precocial) state also enlarged their telencephalon by delaying telencephalic neurogenesis, we examined brain development in geese, ducks, turkeys and chickens, which are all precocial. Whereas the telencephalon occupies less than 55 per cent of the brain in chickens and turkeys, it occupies more than 65 per cent in ducks and geese. To determine how these species differences in adult brain region proportions arise during development, we examined brain maturation (i.e. neurogenesis timing) and estimated telencephalon, tectum and medulla volumes from serial Nissl-stained sections in the four species. We found that incubation time predicts the timing of neurogenesis in all major brain regions and that the telencephalon is proportionally larger in ducks and geese before telencephalic neurogenesis begins. These findings demonstrate that the expansion of the telencephalon in ducks and geese is achieved by altering development prior to neurogenesis onset. Thus, precocial and altricial species evolved different developmental strategies to expand their telencephalon. PMID:19605398

  6. Developmental basis for telencephalon expansion in waterfowl: enlargement prior to neurogenesis.

    PubMed

    Charvet, Christine J; Striedter, Georg F

    2009-10-07

    Some altricial and some precocial species of birds have evolved enlarged telencephalons compared with other birds. Previous work has shown that finches and parakeets, two species that hatch in an immature (i.e. altricial) state, enlarged their telencephalon by delaying telencephalic neurogenesis. To determine whether species that hatch in a relatively mature (i.e. precocial) state also enlarged their telencephalon by delaying telencephalic neurogenesis, we examined brain development in geese, ducks, turkeys and chickens, which are all precocial. Whereas the telencephalon occupies less than 55 per cent of the brain in chickens and turkeys, it occupies more than 65 per cent in ducks and geese. To determine how these species differences in adult brain region proportions arise during development, we examined brain maturation (i.e. neurogenesis timing) and estimated telencephalon, tectum and medulla volumes from serial Nissl-stained sections in the four species. We found that incubation time predicts the timing of neurogenesis in all major brain regions and that the telencephalon is proportionally larger in ducks and geese before telencephalic neurogenesis begins. These findings demonstrate that the expansion of the telencephalon in ducks and geese is achieved by altering development prior to neurogenesis onset. Thus, precocial and altricial species evolved different developmental strategies to expand their telencephalon.

  7. Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

    PubMed

    Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

    2014-08-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.

  8. Hearing loss and enlarged internal auditory canal in children.

    PubMed

    Santos, Saturnino; Domínguez, M Jesús; Cervera, Javier; Suárez, Alicia; Bueno, Antonio; Bartolomé, Margarita; López, Rafael

    2014-01-01

    Among the temporal bone abnormalities that can be found in the etiological study of paediatric sensorineural hearing loss (SNHL) by imaging techniques, those related to the internal auditory canal (IAC) are the least frequent. The most prevalent of these abnormalities that is associated with SNHL is stenotic IAC due to its association with cochlear nerve deficiencies. Less frequent and less concomitant with SNHL is the finding of an enlarged IAC (>8mm). Retrospective and descriptive review of clinical associations, imaging, audiological patterns and treatment of 9 children with hearing loss and enlarged IAC in the period 1999 to 2012. Two groups of patients are described. The first, without association with vestibulocochlear dysplasias, consisted of: 2 patients with SNHL without other temporal bone or systemic abnormalities, one with bilateral mixed HL from chromosome 18q deletion, one with a genetic X-linked DFN3 hearing loss, one with unilateral hearing loss in neurofibromatosis type 2 with bilateral acoustic neuroma, and one with unilateral hearing loss with cochlear nerve deficiency. The second group, with association with vestibulocochlear dysplasias, was comprised of: one patient with moderate bilateral mixed hearing loss in branchio-oto-renal syndrome, one with profound unilateral SNHL with recurrent meningitis, and another with profound bilateral SNHL with congenital hypothyroidism. The presence of an enlarged IAC in children can be found in different clinical and audiological settings with relevancies that can range from life-threatening situations, such as recurrent meningitis, to isolated hearing loss with no other associations. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  9. Brain abnormality segmentation based on l1-norm minimization

    NASA Astrophysics Data System (ADS)

    Zeng, Ke; Erus, Guray; Tanwar, Manoj; Davatzikos, Christos

    2014-03-01

    We present a method that uses sparse representations to model the inter-individual variability of healthy anatomy from a limited number of normal medical images. Abnormalities in MR images are then defined as deviations from the normal variation. More precisely, we model an abnormal (pathological) signal y as the superposition of a normal part ~y that can be sparsely represented under an example-based dictionary, and an abnormal part r. Motivated by a dense error correction scheme recently proposed for sparse signal recovery, we use l1- norm minimization to separate ~y and r. We extend the existing framework, which was mainly used on robust face recognition in a discriminative setting, to address challenges of brain image analysis, particularly the high dimensionality and low sample size problem. The dictionary is constructed from local image patches extracted from training images aligned using smooth transformations, together with minor perturbations of those patches. A multi-scale sliding-window scheme is applied to capture anatomical variations ranging from fine and localized to coarser and more global. The statistical significance of the abnormality term r is obtained by comparison to its empirical distribution through cross-validation, and is used to assign an abnormality score to each voxel. In our validation experiments the method is applied for segmenting abnormalities on 2-D slices of FLAIR images, and we obtain segmentation results consistent with the expert-defined masks.

  10. Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities.

    PubMed

    Lee, Jin Sook; Byun, Christine K; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Ji Eun; Hwang, Yong Seung; Seong, Moon-Woo; Park, Sung Sup; Kim, Ki Joong; Chae, Jong-Hee

    2015-04-01

    Rubinstein-Taybi syndrome (RSTS) is one of the neurodevelopmental disorders caused by mutations of epigenetic genes. The CREBBP gene is the most common causative gene, encoding the CREB-binding protein with histone acetyltransferase (HAT) activity, an epigenetic modulator. To date, there have been few reports on the structural abnormalities of the brain in RSTS patients. In addition, there are no reports on the analysis of CREBBP mutations in Korean RSTS patients. We performed mutational analyses on 16 unrelated patients with RSTS, with diagnosis based on the typical clinical features. Their medical records and brain MRI images were reviewed retrospectively. Ten of 16 patients (62.5%) had mutations in the CREBBP gene. The mutations included five frameshift mutations (31.2%), two nonsense mutations (12.5%), and three multiexon deletions (18.8%). There were no remarkable significant differences in the clinical features between those with and without a CREBBP mutation, although brain MRI abnormalities were more frequently observed in those with a CREBBP mutation. Seven of 10 patients in whom brain imaging was performed had structural abnormalities, including Chiari malformation type 1, thinning of the corpus callosum, and delayed myelination. There were no differences in delayed development or cognitive impairment between those with and without abnormal brain images, while epilepsy was involved in two patients who had abnormalities on brain MRI images. We investigated the spectrum of CREBBP mutations in Korean patients with RSTS for the first time. Eight novel mutations extended the genetic spectrum of CREBBP mutations in RSTS patients. This is also the first study showing the prevalence and spectrum of abnormalities on brain MRI in RSTS patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Back to the future: estimating pre-injury brain volume in patients with traumatic brain injury.

    PubMed

    Ross, David E; Ochs, Alfred L; D Zannoni, Megan; Seabaugh, Jan M

    2014-11-15

    A recent meta-analysis by Hedman et al. allows for accurate estimation of brain volume changes throughout the life span. Additionally, Tate et al. showed that intracranial volume at a later point in life can be used to estimate reliably brain volume at an earlier point in life. These advancements were combined to create a model which allowed the estimation of brain volume just prior to injury in a group of patients with mild or moderate traumatic brain injury (TBI). This volume estimation model was used in combination with actual measurements of brain volume to test hypotheses about progressive brain volume changes in the patients. Twenty six patients with mild or moderate TBI were compared to 20 normal control subjects. NeuroQuant® was used to measure brain MRI volume. Brain volume after the injury (from MRI scans performed at t1 and t2) was compared to brain volume just before the injury (volume estimation at t0) using longitudinal designs. Groups were compared with respect to volume changes in whole brain parenchyma (WBP) and its 3 major subdivisions: cortical gray matter (GM), cerebral white matter (CWM) and subcortical nuclei+infratentorial regions (SCN+IFT). Using the normal control data, the volume estimation model was tested by comparing measured brain volume to estimated brain volume; reliability ranged from good to excellent. During the initial phase after injury (t0-t1), the TBI patients had abnormally rapid atrophy of WBP and CWM, and abnormally rapid enlargement of SCN+IFT. Rates of volume change during t0-t1 correlated with cross-sectional measures of volume change at t1, supporting the internal reliability of the volume estimation model. A logistic regression analysis using the volume change data produced a function which perfectly predicted group membership (TBI patients vs. normal control subjects). During the first few months after injury, patients with mild or moderate TBI have rapid atrophy of WBP and CWM, and rapid enlargement of SCN+IFT. The

  12. Structural brain abnormalities in Cushing's syndrome.

    PubMed

    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.

  13. Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence.

    PubMed

    Tolomeo, S; Gray, S; Matthews, K; Steele, J D; Baldacchino, A

    2016-10-01

    Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

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

    PubMed Central

    Janušonis, Skirmantas

    2005-01-01

    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 experimental studies. PMID

  15. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study.

    PubMed

    Grachev, I D; Fredrickson, B E; Apkarian, A V

    2000-12-15

    The neurobiology of chronic pain, including chronic back pain, is unknown. Structural imaging studies of the spine cannot explain all cases of chronic back pain. Functional brain imaging studies indicate that the brain activation patterns are different between chronic pain patients and normal subjects, and the thalamus, and prefrontal and cingulate cortices are involved in some types of chronic pain. Animal models of chronic pain suggest abnormal spinal cord chemistry. Does chronic pain cause brain chemistry changes? We examined brain chemistry changes in patients with chronic back pain using in vivo single- voxel proton magnetic resonance spectroscopy ((1)H-MRS). In vivo (1)H-MRS was used to measure relative concentrations of N-acetyl aspartate, creatine, choline, glutamate, glutamine, gamma-aminobutyric acid, inositol, glucose and lactate in relation to the concentration of creatine. These measurements were performed in six brain regions of nine chronic low back pain patients and 11 normal volunteers. All chronic back pain subjects underwent clinical evaluation and perceptual measures of pain and anxiety. We show that chronic back pain alters the human brain chemistry. Reductions of N-acetyl aspartate and glucose were demonstrated in the dorsolateral prefrontal cortex. Cingulate, sensorimotor, and other brain regions showed no chemical concentration differences. In chronic back pain, the interrelationship between chemicals within and across brain regions was abnormal, and there was a specific relationship between regional chemicals and perceptual measures of pain and anxiety. These findings provide direct evidence of abnormal brain chemistry in chronic back pain, which may be useful in diagnosis and future development of more effective pharmacological treatments.

  16. Abnormal brain structure implicated in stimulant drug addiction.

    PubMed

    Ersche, Karen D; Jones, P Simon; Williams, Guy B; Turton, Abigail J; Robbins, Trevor W; Bullmore, Edward T

    2012-02-03

    Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.

  17. Enlarging the scope: grasping brain complexity

    PubMed Central

    Tognoli, Emmanuelle; Kelso, J. A. Scott

    2014-01-01

    To further advance our understanding of the brain, new concepts and theories are needed. In particular, the ability of the brain to create information flows must be reconciled with its propensity for synchronization and mass action. The theoretical and empirical framework of Coordination Dynamics, a key aspect of which is metastability, are presented as a starting point to study the interplay of integrative and segregative tendencies that are expressed in space and time during the normal course of brain and behavioral function. Some recent shifts in perspective are emphasized, that may ultimately lead to a better understanding of brain complexity. PMID:25009476

  18. Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex.

    PubMed

    Gaser, Christian; Nenadic, Igor; Buchsbaum, Bradley R; Hazlett, Erin A; Buchsbaum, Monte S

    2004-01-01

    Enlargement of the lateral ventricles is among the most frequently reported macroscopic brain structural changes in schizophrenia, although variable in extent and localization. The authors investigated whether ventricular enlargement is related to regionally specific volume loss. High-resolution magnetic resonance imaging scans from 39 patients with schizophrenia were analyzed with deformation-based morphometry, a voxel-wise whole brain morphometric technique. Significant negative correlations with the ventricle-brain ratio were found for voxels in the left and right thalamus and posterior putamen and in the left superior temporal gyrus and insula. Thalamic shrinkage, especially of medial nuclei and the adjacent striatum and insular cortex, appear to be important contributors to ventricular enlargement in schizophrenia.

  19. Enlarged thalamostriate vein causing unilateral Monro foramen obstruction. Case report.

    PubMed

    Leonardo, Jody; Grand, Walter

    2009-06-01

    Causes of unilateral hydrocephalus resulting from an obstruction at the Monro foramen include foraminal atresia, tumors, gliosis, contralateral shunting, and infectious and inflammatory conditions. However, few reports in the literature cite vascular lesions as the cause of the obstruction. To their knowledge, the authors present the first report of unilateral hydrocephalus occurring due to an abnormally enlarged thalamostriate vein independent of an arteriovenous malformation or developmental venous angioma. The condition was treated successfully by endoscopic septum pellucidum fenestration. A 28-year-old man was referred for evaluation due to a 10-year history of chronic headaches that worsened in severity over the past year. A CT scan of the head revealed unilateral right ventricular dilation. Cranial MR imaging with and without contrast administration showed a dilated right thalamostriate-internal vein complex without any evidence of associated arteriovenous malformation or venous angioma. Endoscopic exploration of the right lateral ventricle showed an enlarged subependymal thalamostriate vein obstructing the Monro foramen. An endoscopic fenestration of the septum pellucidum was performed, resulting in alleviation of the patient's symptoms. Abnormally enlarged venous structures may cause obstructive unilateral hydrocephalus and can be a rare cause of chronic, intermittent headaches in adults. Endoscopic fenestration of the septum pellucidum is an effective treatment.

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

    PubMed

    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.

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

    PubMed Central

    Silva, Mauro S.B.; Prescott, Melanie; Campbell, Rebecca E.

    2018-01-01

    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. PMID:29618656

  2. Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

    PubMed

    Saleem, Sahar N

    2013-07-01

    Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

  3. Functional brain abnormalities in major depressive disorder using the Hilbert-Huang transform.

    PubMed

    Yu, Haibin; Li, Feng; Wu, Tong; Li, Rui; Yao, Li; Wang, Chuanyue; Wu, Xia

    2018-02-09

    Major depressive disorder is a common disease worldwide, which is characterized by significant and persistent depression. Non-invasive accessory diagnosis of depression can be performed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the fMRI signal may not satisfy linearity and stationarity. The Hilbert-Huang transform (HHT) is an adaptive time-frequency localization analysis method suitable for nonlinear and non-stationary signals. The objective of this study was to apply the HHT to rs-fMRI to find the abnormal brain areas of patients with depression. A total of 35 patients with depression and 37 healthy controls were subjected to rs-fMRI. The HHT was performed to extract the Hilbert-weighted mean frequency of the rs-fMRI signals, and multivariate receiver operating characteristic analysis was applied to find the abnormal brain regions with high sensitivity and specificity. We observed differences in Hilbert-weighted mean frequency between the patients and healthy controls mainly in the right hippocampus, right parahippocampal gyrus, left amygdala, and left and right caudate nucleus. Subsequently, the above-mentioned regions were included in the results obtained from the compared region homogeneity and the fractional amplitude of low frequency fluctuation method. We found brain regions with differences in the Hilbert-weighted mean frequency, and examined their sensitivity and specificity, which suggested a potential neuroimaging biomarker to distinguish between patients with depression and healthy controls. We further clarified the pathophysiological abnormality of these regions for the population with major depressive disorder.

  4. Chronic inflammatory gingival enlargement associated with orthodontic therapy--a case report.

    PubMed

    Jadhav, Tanya; Bhat, K Mahalinga; Bhat, G Subraya; Varghese, Jothi M

    2013-02-01

    Gingival enlargement, also synonymous with the terms gingival hyperplasia or hypertrophy, is defined as an abnormal overgrowth of gingival tissues. A case of a 19-year-old male presenting with maxillary and mandibular chronic inflammatory gingival enlargement associated with prolonged orthodontic therapy is reported here. Surgical therapy was carried out to provide a good aesthetic outcome. No recurrence was reported at the end of 1 year. The importance of patient motivation and compliance during and after therapy as a critical factor in the success of treatment has also been highlighted through this case report.

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

    PubMed Central

    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

  6. Neuroendocrine abnormalities in patients with traumatic brain injury

    NASA Technical Reports Server (NTRS)

    Yuan, X. Q.; Wade, C. E.

    1991-01-01

    This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture

  7. New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

    PubMed

    Kidokoro, H; Neil, J J; Inder, T E

    2013-01-01

    WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

  8. Fetal adrenal gland enlargement - prenatal and postnatal management.

    PubMed

    Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria

    2017-11-01

    The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date

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

    PubMed

    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.

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

    PubMed

    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.

  11. Abnormal Spontaneous Brain Activity in Patients With Anisometropic Amblyopia Using Resting-State Functional Magnetic Resonance Imaging.

    PubMed

    Tang, Angcang; Chen, Taolin; Zhang, Junran; Gong, Qiyong; Liu, Longqian

    2017-09-01

    To explore the abnormality of spontaneous activity in patients with anisometropic amblyopia under resting-state functional magnetic resonance imaging (Rs-fMRI). Twenty-four participants were split into two groups. The anisometropic amblyopia group had 10 patients, all of whom had anisometropic amblyopia of the right eye, and the control group had 14 healthy subjects. All participants underwent Rs-fMRI scanning. Measurement of amplitude of low frequency fluctuations of the brain, which is a measure of the amplitudes of spontaneous brain activity, was used to investigate brain changes between the anisometropic amblyopia and control groups. Compared with an age- and gender-matched control group, the anisometropic amblyopia group showed increased amplitude of low frequency fluctuations of spontaneous brain activity in the left superior temporal gyrus, the left inferior parietal lobe, the left pons, and the right inferior semi-lunar lobe. The anisometropic amblyopia group also showed decreased amplitude of low frequency fluctuations in the bilateral medial frontal gyrus. This study demonstrated abnormal spontaneous brain activities in patients with anisometropic amblyopia under Rs-fMRI, and these abnormalities might contribute to the neuropathological mechanisms of anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(5):303-310.]. Copyright 2017, SLACK Incorporated.

  12. Diabetes synergistically exacerbates poststroke dementia and tau abnormality in brain.

    PubMed

    Zhang, Ting; Pan, Bai-Shen; Sun, Guang-Chun; Sun, Xiao; Sun, Feng-Yan

    2010-07-01

    This study investigated whether exacerbation of poststroke dementia by diabetes associated abnormal tau phosphorylation and its mechanism. Streptozotocin (STZ) injection and/or a high fat diet (HFD) were used to treat rats to induce type 1 and 2 diabetes. Animals were randomly divided into STZ, HFD, STZ-HFD, and normal diet (NPD) groups. Focal ischemic stroke was induced by middle cerebral artery occlusion (MCAO). Cognitive function was tested by the Morris water maze. STZ or STZ-HFD treatment exacerbated ischemia-induced cognitive deficits, brain infarction and reduction of synaptophysin expression. Moreover, we found that diabetes further increased AT8, a marker of hyperphosphorylated tau, protein and immunopositive stained cells in the hippocampus of rats following MCAO while reduced the level of phosphorylated glycogen synthase kinase 3-beta at serine-9 residues (p-ser9-GSK-3beta), indicating activation of GSK-3beta. We conclude that diabetes further deteriorates ischemia-induced brain damage and cognitive deficits which may be associated with abnormal phosphorylation of tau as well as activation of GSK-3beta. These findings may be helpful for developing new strategies to prevent/delay formation of poststroke dementia in patients with diabetes. 2010 Elsevier Ltd. All rights reserved.

  13. Enlarged perivascular spaces and cognitive impairment after stroke and transient ischemic attack.

    PubMed

    Arba, Francesco; Quinn, Terence J; Hankey, Graeme J; Lees, Kennedy R; Wardlaw, Joanna M; Ali, Myzoon; Inzitari, Domenico

    2018-01-01

    Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22-2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03-2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that

  14. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults.

    PubMed

    Virtanen, J K; Siscovick, D S; Longstreth, W T; Kuller, L H; Mozaffarian, D

    2008-08-05

    To investigate the association between fish consumption and subclinical brain abnormalities. In the population-based Cardiovascular Health Study, 3,660 participants age > or =65 underwent an MRI scan in 1992-1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish > or =3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54-1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.

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

    PubMed

    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.

  16. Influence of History of Brain Disease or Brain Trauma on Psychopathological Abnormality in Young Male in Korea : Analysis of Multiphasic Personal Inventory Test

    PubMed Central

    Paik, Ho Kyu; Oh, Chang-Hyun; Choi, Kang; Kim, Chul-Eung; Yoon, Seung Hwan

    2011-01-01

    Objective The purpose of this study is to confirm whether brain disease or brain trauma actually affect psychopathology in young male group in Korea. Methods The authors manually reviewed the result of Korean military multiphasic personal inventory (KMPI) in the examination of conscription in Korea from January 2008 to May 2010. There were total 237 young males in this review. Normal volunteers group (n=150) was composed of those who do not have history of brain disease or brain trauma. Brain disease group (n=33) was consisted of those with history of brain disease. Brain trauma group (n=54) was consisted of those with history of brain trauma. The results of KMPI in each group were compared. Results Abnormal results of KMPI were found in both brain disease and trauma groups. In the brain disease group, higher tendencies of faking bad response, anxiety, depression, somatization, personality disorder, schizophrenic and paranoid psychopathy was observed and compared to the normal volunteers group. In the brain trauma group, higher tendencies of faking-good, depression, somatization and personality disorder was observed and compared to the normal volunteers group. Conclusion Young male with history of brain disease or brain trauma may have higher tendencies to have abnormal results of multiphasic personal inventory test compared to young male without history of brain disease or brain trauma, suggesting that damaged brain may cause psychopathology in young male group in Korea. PMID:22053230

  17. Simulation of realistic abnormal SPECT brain perfusion images: application in semi-quantitative analysis

    NASA Astrophysics Data System (ADS)

    Ward, T.; Fleming, J. S.; Hoffmann, S. M. A.; Kemp, P. M.

    2005-11-01

    Simulation is useful in the validation of functional image analysis methods, particularly when considering the number of analysis techniques currently available lacking thorough validation. Problems exist with current simulation methods due to long run times or unrealistic results making it problematic to generate complete datasets. A method is presented for simulating known abnormalities within normal brain SPECT images using a measured point spread function (PSF), and incorporating a stereotactic atlas of the brain for anatomical positioning. This allows for the simulation of realistic images through the use of prior information regarding disease progression. SPECT images of cerebral perfusion have been generated consisting of a control database and a group of simulated abnormal subjects that are to be used in a UK audit of analysis methods. The abnormality is defined in the stereotactic space, then transformed to the individual subject space, convolved with a measured PSF and removed from the normal subject image. The dataset was analysed using SPM99 (Wellcome Department of Imaging Neuroscience, University College, London) and the MarsBaR volume of interest (VOI) analysis toolbox. The results were evaluated by comparison with the known ground truth. The analysis showed improvement when using a smoothing kernel equal to system resolution over the slightly larger kernel used routinely. Significant correlation was found between effective volume of a simulated abnormality and the detected size using SPM99. Improvements in VOI analysis sensitivity were found when using the region median over the region mean. The method and dataset provide an efficient methodology for use in the comparison and cross validation of semi-quantitative analysis methods in brain SPECT, and allow the optimization of analysis parameters.

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

    PubMed

    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.

  19. Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

    PubMed

    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. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

  20. Rapid Morphological Brain Abnormalities during Acute Methamphetamine Intoxication in the Rat. An Experimental study using Light and Electron Microscopy

    PubMed Central

    Sharma, Hari S.; Kiyatkin, Eugene A.

    2009-01-01

    This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (iv) catheter were exposed to METH (9 mg/kg) at standard (23°C) and warm (29°C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological levels (38–42°C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5°C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na+, K+, Cl−) contents, immunostained for albumin and glial fibrillary acidic protein, and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29°C than 23°C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse. PMID:18773954

  1. A priori collaboration in population imaging: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement consortium.

    PubMed

    Adams, Hieab H H; Hilal, Saima; Schwingenschuh, Petra; Wittfeld, Katharina; van der Lee, Sven J; DeCarli, Charles; Vernooij, Meike W; Katschnig-Winter, Petra; Habes, Mohamad; Chen, Christopher; Seshadri, Sudha; van Duijn, Cornelia M; Ikram, M Kamran; Grabe, Hans J; Schmidt, Reinhold; Ikram, M Arfan

    2015-12-01

    Virchow-Robin spaces (VRS), or perivascular spaces, are compartments of interstitial fluid enclosing cerebral blood vessels and are potential imaging markers of various underlying brain pathologies. Despite a growing interest in the study of enlarged VRS, the heterogeneity in rating and quantification methods combined with small sample sizes have so far hampered advancement in the field. The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement (UNIVRSE) consortium was established with primary aims to harmonize rating and analysis (www.uconsortium.org). The UNIVRSE consortium brings together 13 (sub)cohorts from five countries, totaling 16,000 subjects and over 25,000 scans. Eight different magnetic resonance imaging protocols were used in the consortium. VRS rating was harmonized using a validated protocol that was developed by the two founding members, with high reliability independent of scanner type, rater experience, or concomitant brain pathology. Initial analyses revealed risk factors for enlarged VRS including increased age, sex, high blood pressure, brain infarcts, and white matter lesions, but this varied by brain region. Early collaborative efforts between cohort studies with respect to data harmonization and joint analyses can advance the field of population (neuro)imaging. The UNIVRSE consortium will focus efforts on other potential correlates of enlarged VRS, including genetics, cognition, stroke, and dementia.

  2. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  3. Abnormal Neural Connectivity in Schizophrenia and fMRI-Brain-Computer Interface as a Potential Therapeutic Approach

    PubMed Central

    Ruiz, Sergio; Birbaumer, Niels; Sitaram, Ranganatha

    2012-01-01

    Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the “abnormal neural connectivity hypothesis.” In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI) are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia. The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem. PMID:23525496

  4. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

    PubMed Central

    Brady, Roscoe O; McCarthy, Julie M; Prescot, Andrew P; Jensen, J Eric; Cooper, Alissa J; Cohen, Bruce M; Renshaw, Perry F; Ongür, Dost

    2017-01-01

    Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition. PMID:23634979

  5. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

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

    Fujibayashi, Y.; Yamamoto, S.; Waki, A.

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies.more » In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.« less

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

    PubMed

    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

  7. Morphometric abnormalities of the lateral ventricles in methamphetamine-dependent subjects☆

    PubMed Central

    Jeong, Hyeonseok S.; Lee, Sunho; Yoon, Sujung; Jung, Jiyoung J.; Cho, Han Byul; Kim, Binna N.; Ma, Jiyoung; Ko, Eun; Im, Jooyeon Jamie; Ban, Soonhyun; Renshaw, Perry F.; Lyoo, In Kyoon

    2017-01-01

    Background The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects. Methods High-resolution brain structural images were obtained from 37 methamphetamine-dependent subjects and 25 demographically matched healthy individuals. Using a combined volumetric and surface-based morphometric approach, the structural variability of the lateral ventricles, with respect to extent and location, was examined. Results Methamphetamine-dependent subjects had an enlarged right lateral ventricle compared with healthy individuals. Morphometric analysis revealed a region-specific pattern of lateral ventricular expansion associated with methamphetamine dependence, which was mainly distributed in the areas adjacent to the ventral striatum, medial prefrontal cortex, and thalamus. Conclusions Patterns of shape decomposition in the lateral ventricles may have relevance to the structural vulnerability of the prefrontal-ventral striatal-thalamic circuit to methamphetamine-induced neurotoxicity. PMID:23769159

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

    PubMed

    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 < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) 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 < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower 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.

  9. Neuroanatomical abnormalities in chronic tinnitus in the human brain

    PubMed Central

    Adjamian, Peyman; Hall, Deborah A.; Palmer, Alan R.; Allan, Thomas W.; Langers, Dave R.M.

    2014-01-01

    In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research. PMID:24892904

  10. Human Brain Abnormalities Associated With Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder

    PubMed Central

    Jarmasz, Jessica S.; Basalah, Duaa A.; Chudley, Albert E.; Del Bigio, Marc R.

    2017-01-01

    Abstract Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980–2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings were categorized into 5 age groups. Alcohol exposure was difficult to quantify. When documented, almost all mothers smoked tobacco, many abused other substances, and prenatal care was poor or nonexistent. Placental abnormalities were common (68%) in fetal cases. We identified micrencephaly (brain weight <5th percentile) in 31, neural tube defects in 5, isolated hydrocephalus in 6, corpus callosum defects in 6 (including some with complex anomalies), probable prenatal ischemic lesions in 5 (excluding complications of prematurity), minor subarachnoid heterotopias in 4, holoprosencephaly in 1, lissencephaly in 1, and cardiac anomalies in 26 cases. The brain abnormalities associated with prenatal alcohol exposure are varied; cause–effect relationships cannot be determined. FASD is likely not a monotoxic disorder. The animal experimental literature, which emphasizes controlled exposure to ethanol alone, is therefore inadequate. Prevention must be the main societal goal, however, a clear understanding of the neuropathology is necessary for provision of care to individuals already affected. PMID:28859338

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

    PubMed

    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.

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

    PubMed Central

    Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G.; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A.; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J.; Diwakar, Mithun; Risbrough, Victoria B.; Ji, Zhengwei; Huang, Charles W.; Chang, Douglas G.; Harrington, Deborah L.; Muzzatti, Laura; Canive, Jose M.; Christopher Edgar, J.; Chen, Yu-Han; Lee, Roland R.

    2014-01-01

    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. PMID:25009772

  13. Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors.

    PubMed

    Li, Matthew D; Forkert, Nils D; Kundu, Palak; Ambler, Cheryl; Lober, Robert M; Burns, Terry C; Barnes, Patrick D; Gibbs, Iris C; Grant, Gerald A; Fisher, Paul G; Cheshier, Samuel H; Campen, Cynthia J; Monje, Michelle; Yeom, Kristen W

    2017-06-01

    To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Clinical correlates of enlarged cavum septum pellucidum in schizophrenia: A revisit through computed tomography.

    PubMed

    Srivastava, Naveen Kumar; Khanra, Sourav; Chail, Vivek; Khess, Christoday R J

    2015-06-01

    Like prevalence of abnormal cavum septum pellucidum in patients of schizophrenia remains controversial, its role in clinical outcome, duration of illness and effect on treatment remains less understood as well. Our study examined clinical correlates of enlarged cavum septum pellucidum in schizophrenia. A total of 139 patients diagnosed with schizophrenia during the year 2012 and 2013 were taken for the study. We compared them in respect to the presence and absence of enlarged cavum septum pellucidum. We found 16 patients with enlarged cavum septum pellucidum and were compared with those without enlarged cavum septum pellucidum for socio-demographic and clinical variables. We also correlated these clinical variables with dimension of cavum septum pellucidum. We found statistically significant increased current age and duration of illness in patients with enlarged cavum septum pellucidum. The implications of these findings are discussed with possible confounding effect of current age on neuroimaging. No meaningful correlation was found. No difference in clinical variables was found. Retrospective design and use of computed tomography were limitation of our study. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

    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 < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for 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

  16. Enlarged Adenoids

    MedlinePlus

    ... Feelings Expert Answers Q&A Movies & More for Teens Teens site Sitio para adolescentes Body Mind Sexual Health ... Educators Search English Español Enlarged Adenoids KidsHealth / For Teens / Enlarged Adenoids What's in this article? Symptoms of ...

  17. Quantitation of specific binding ratio in 123I-FP-CIT SPECT: accurate processing strategy for cerebral ventricular enlargement with use of 3D-striatal digital brain phantom.

    PubMed

    Furuta, Akihiro; Onishi, Hideo; Amijima, Hizuru

    2018-06-01

    This study aimed to evaluate the effect of ventricular enlargement on the specific binding ratio (SBR) and to validate the cerebrospinal fluid (CSF)-Mask algorithm for quantitative SBR assessment of 123 I-FP-CIT single-photon emission computed tomography (SPECT) images with the use of a 3D-striatum digital brain (SDB) phantom. Ventricular enlargement was simulated by three-dimensional extensions in a 3D-SDB phantom comprising segments representing the striatum, ventricle, brain parenchyma, and skull bone. The Evans Index (EI) was measured in 3D-SDB phantom images of an enlarged ventricle. Projection data sets were generated from the 3D-SDB phantoms with blurring, scatter, and attenuation. Images were reconstructed using the ordered subset expectation maximization (OSEM) algorithm and corrected for attenuation, scatter, and resolution recovery. We bundled DaTView (Southampton method) with the CSF-Mask processing software for SBR. We assessed SBR with the use of various coefficients (f factor) of the CSF-Mask. Specific binding ratios of 1, 2, 3, 4, and 5 corresponded to SDB phantom simulations with true values. Measured SBRs > 50% that were underestimated with EI increased compared with the true SBR and this trend was outstanding at low SBR. The CSF-Mask improved 20% underestimates and brought the measured SBR closer to the true values at an f factor of 1.0 despite an increase in EI. We connected the linear regression function (y = - 3.53x + 1.95; r = 0.95) with the EI and f factor using root-mean-square error. Processing with CSF-Mask generates accurate quantitative SBR from dopamine transporter SPECT images of patients with ventricular enlargement.

  18. Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

    PubMed

    Pitel, Anne Lise; Segobin, Shailendra H; Ritz, Ludivine; Eustache, Francis; Beaunieux, Hélène

    2015-07-01

    Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks. Copyright © 2014. Published by Elsevier Ltd.

  19. Regional grey matter volume abnormalities in bulimia nervosa and binge-eating disorder.

    PubMed

    Schäfer, Axel; Vaitl, Dieter; Schienle, Anne

    2010-04-01

    This study investigated whether bulimia nervosa (BN) and binge-eating disorder (BED) are associated with structural brain abnormalities. Both disorders share the main symptom binge-eating, but are considered differential diagnoses. We attempted to identify alterations in grey matter volume (GMV) that are present in both psychopathologies as well as disorder-specific GMV characteristics. Such information can help to improve neurobiological models of eating disorders and their classification. A total of 50 participants (patients suffering from BN (purge type), BED, and normal-weight controls) underwent structural MRI scanning. GMV for specific brain regions involved in food/reinforcement processing was analyzed by means of voxel-based morphometry. Both patient groups were characterized by greater volumes of the medial orbitofrontal cortex (OFC) compared to healthy controls. In BN patients, who had increased ventral striatum volumes, body mass index and purging severity were correlated with striatal grey matter volume. Altogether, our data implicate a crucial role of the medial OFC in the studied eating disorders. The structural abnormality might be associated with dysfunctions in food reward processing and/or self-regulation. The bulimia-specific volume enlargement of the ventral striatum is discussed in the framework of negative reinforcement through purging and associated weight regulation. Copyright 2009 Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  1. An enlarged parietal foramen in the late archaic Xujiayao 11 neurocranium from Northern China, and rare anomalies among Pleistocene Homo.

    PubMed

    Wu, Xiu-Jie; Xing, Song; Trinkaus, Erik

    2013-01-01

    We report here a neurocranial abnormality previously undescribed in Pleistocene human fossils, an enlarged parietal foramen (EPF) in the early Late Pleistocene Xujiayao 11 parietal bones from the Xujiayao (Houjiayao) site, northern China. Xujiayao 11 is a pair of partial posteromedial parietal bones from an adult. It exhibits thick cranial vault bones, arachnoid granulations, a deviated posterior sagittal suture, and a unilateral (right) parietal lacuna with a posteriorly-directed and enlarged endocranial vascular sulcus. Differential diagnosis indicates that the perforation is a congenital defect, an enlarged parietal foramen, commonly associated with cerebral venous and cranial vault anomalies. It was not lethal given the individual's age-at-death, but it may have been associated with secondary neurological deficiencies. The fossil constitutes the oldest evidence in human evolution of this very rare condition (a single enlarged parietal foramen). In combination with developmental and degenerative abnormalities in other Pleistocene human remains, it suggests demographic and survival patterns among Pleistocene Homo that led to an elevated frequency of conditions unknown or rare among recent humans.

  2. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse Model

    PubMed Central

    Wei, Ran; Hui, Edward S.; Feldon, Joram; Meyer, Urs; Chung, Sookja; Chua, Siew E.; Sham, Pak C.; Wu, Ed X.; McAlonan, Grainne M.

    2009-01-01

    Objectives Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method We used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. PMID:19629183

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

    DTIC Science & Technology

    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

  6. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

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

    Choi, Hong-Seok; Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060; Choi, Yeong-Gon

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress inmore » scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  7. Abnormal ventricular development in preterm neonates with visually normal MRIs

    NASA Astrophysics Data System (ADS)

    Shi, Jie; Wang, Yalin; Lao, Yi; Ceschin, Rafael; Mi, Liang; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

    2015-12-01

    Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using multivariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.

  8. Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

    PubMed

    Lainhart, Janet E

    2015-03-01

    Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

  9. Brain stem and inner ear abnormalities in children with auditory neuropathy spectrum disorder and cochlear nerve deficiency.

    PubMed

    Huang, B Y; Roche, J P; Buchman, C A; Castillo, M

    2010-11-01

    Cranial abnormalities, including CND, are common in children with ANSD. The purpose of this study was to assess whether CND is associated with brain or inner ear abnormalities in a cohort of children with ANSD. Two neuroradiologists retrospectively reviewed cranial MR imaging examinations in 103 children with ANSD. Brain, cochlear nerve, and temporal bone abnormalities were described and tabulated. Findings were stratified on the basis of the presence and laterality of CND, and differences in the presence of associated inner ear or intracranial abnormalities were assessed by using 2-tailed Fisher exact tests. CND was identified in 33.0% of children and 26.9% of ears with ANSD. Significantly more patients with bilateral CND had intracranial abnormalities than those with unilateral CND (60.0% versus 15.8%; P = .012). Forty percent of patients with bilateral CND, 0% of patients with unilateral CND, and 10.1% of those without CND demonstrated hindbrain malformations. Patients with bilateral CND were more likely to demonstrate hindbrain malformations than patients with normal nerves (P = .01) or unilateral CND (P = .004). Labyrinthine abnormalities were significantly more common in patients with bilateral CND than in those without CND (P ≤ .001). Cochlear anomalies were more common in patients with bilateral versus unilateral CND (P = .01). IAC and cochlear aperture stenosis were more common in those with unilateral and bilateral CND than those without CND (both P < .001). Cochlear and hindbrain abnormalities are significantly more common among patients with ANSD with bilateral CND compared with those with at least 1 intact cochlear nerve.

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

    PubMed

    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.

  11. Abnormal brain activation during directed forgetting of negative memory in depressed patients.

    PubMed

    Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2016-01-15

    The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

    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

  13. Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity.

    PubMed

    Yau, Po Lai; Kang, Esther H; Javier, David C; Convit, Antonio

    2014-08-01

    To ascertain whether pediatric obesity without clinically significant insulin resistance (IR) impacts brain structure and function. Thirty obese and 30 matched lean adolescents, all without clinically significant IR or a diagnosis of metabolic syndrome (MetS), received comprehensive endocrine, neuropsychological, and MRI evaluations. Relative to lean adolescents, obese non-IR adolescents had significantly lower academic achievement (i.e., arithmetic and spelling) and tended to score lower on working memory, attention, psychomotor efficiency, and mental flexibility. In line with our prior work on adolescent MetS, memory was unaffected in uncomplicated obesity. Reductions in the thickness of the orbitofrontal and anterior cingulate cortices as well as reductions of microstructural integrity in major white matter tracts without gross volume changes were also uncovered. It was documented, for the first time, that adolescents with uncomplicated obesity already have subtle brain alterations and lower performance in selective cognitive domains. When interpreting these preliminary data in the context of our prior reports of similar, but more extensive brain findings in obese adolescents with MetS and T2DM, it was concluded that "uncomplicated" obesity may also result in subtle brain alterations, suggesting a possible dose effect with more severe metabolic dysregulation giving rise to greater abnormalities. Copyright © 2014 The Obesity Society.

  14. Cerebral perfusion abnormalities in therapy-resistant epilepsy in childhood: comparison between EEG, MRI and 99Tcm-ECD brain SPET.

    PubMed

    Vattimo, A; Burroni, L; Bertelli, P; Volterrani, D; Vella, A

    1996-01-01

    We performed 99Tcm-ethyl cysteinate dimer (ECD) interictal single photon emission tomography (SPET) in 26 children with severe therapy-resistant epilepsy. All the children underwent a detailed clinical examination, an electroencephalogram (EEG) investigation and brain magnetic resonance imaging (MRI). In 21 of the 26 children, SPET demonstrated brain blood flow abnormalities, in 13 cases in the same territories that showed EEG alterations. MRI showed structural lesions in 6 of the 26 children, while SPET imaging confirmed these abnormalities in only 5 children. The lesion not detected on SPET was shown to be 3 mm thick on MRI. Five symptomatic patients had normal SPET. In one of these patients, the EEG findings were normal and MRI revealed a small calcific nodule (4 mm thick); in the others, the EEG showed non-focal but diffuse abnormalities. These data confirm that brain SPET is sensitive in detecting and localizing hypoperfused areas that could be associated with epileptic foci in this group of patients, even when the MRI image is normal.

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

    PubMed

    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.

  16. Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging.

    PubMed

    Grover, V P B; Southern, L; Dyson, J K; Kim, J U; Crossey, M M E; Wylezinska-Arridge, M; Patel, N; Fitzpatrick, J A; Bak-Bol, A; Waldman, A D; Alexander, G J; Mells, G F; Chapman, R W; Jones, D E J; Taylor-Robinson, S D

    2016-11-01

    Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

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

    PubMed Central

    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

  18. Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury.

    PubMed

    Isokuortti, Harri; Iverson, Grant L; Silverberg, Noah D; Kataja, Anneli; Brander, Antti; Öhman, Juha; Luoto, Teemu M

    2018-01-12

    OBJECTIVE The incidence of intracranial abnormalities after mild traumatic brain injury (TBI) varies widely across studies. This study describes the characteristics of intracranial abnormalities (acute/preexisting) in a large representative sample of head-injured patients who underwent CT imaging in an emergency department. METHODS CT scans were systematically analyzed/coded in the TBI Common Data Elements framework. Logistic regression modeling was used to quantify risk factors for traumatic intracranial abnormalities in patients with mild TBIs. This cohort included all patients who were treated at the emergency department of the Tampere University Hospital (between 2010 and 2012) and who had undergone head CT imaging after suffering a suspected TBI (n = 3023), including 2766 with mild TBI and a reference group with moderate to severe TBI. RESULTS The most common traumatic lesions seen on CT scans obtained in patients with mild TBIs and those with moderate to severe TBIs were subdural hematomas, subarachnoid hemorrhages, and contusions. Every sixth patient (16.1%) with mild TBI had an intracranial lesion compared with 5 of 6 patients (85.6%) in the group with moderate to severe TBI. The distribution of different types of acute traumatic lesions was similar among mild and moderate/severe TBI groups. Preexisting brain lesions were a more common CT finding among patients with mild TBIs than those with moderate to severe TBIs. Having a past traumatic lesion was associated with increased risk for an acute traumatic lesion but neurodegenerative and ischemic lesions were not. A lower Glasgow Coma Scale score, male sex, older age, falls, and chronic alcohol abuse were associated with higher risk of acute intracranial lesion in patients with mild TBI. CONCLUSIONS These findings underscore the heterogeneity of neuropathology associated with the mild TBI classification. Preexisting brain lesions are common in patients with mild TBI, and the incidence of preexisting lesions

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

    PubMed

    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.

  20. Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

    PubMed Central

    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 focal analyses. Methods 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. Results 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. Conclusions 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. PMID:24144356

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

    PubMed

    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.

  2. High Risk of Dementia in Ventricular Enlargement with Normal Pressure Hydrocephalus Related Symptoms1.

    PubMed

    Koivisto, Anne M; Kurki, Mitja I; Alafuzoff, Irina; Sutela, Anna; Rummukainen, Jaana; Savolainen, Sakari; Vanninen, Ritva; Jääskeläinen, Juha E; Soininen, Hilkka; Leinonen, Ville

    2016-03-22

    Differential diagnosis of ventricular enlargement with normal pressure hydrocephalus (NPH) related symptoms is challenging. Patients with enlarged ventricles often manifest cognitive deterioration but their long-term outcome is not well known. We aim to evaluate long-term cognitive outcome in patients with enlarged ventricles and clinically suspected NPH. A neurologist and a neurosurgeon clinically evaluated 468 patients with enlarged ventricles and suspected NPH using radiological methods, intraventricular pressure monitoring, and frontal cortical brain biopsy. The neurologist confirmed final diagnoses after a median follow-up interval of 4.8 years. Altogether, 232 patients (50%) with enlarged ventricles did not fulfill the criteria for shunt surgery. The incidence of dementia among patients with enlarged ventricles, and at least one NPH-related symptom with adequate follow-up data (n = 446) was high, varying from 77 (iNPH, shunt responders) to 141/1000 person-years (non-shunted patients with enlarged ventricles). At the end of the follow-up, 59% of all these patients were demented. The demented population comprised 73% of non-shunted patients with enlarged ventricles, 63% of shunted iNPH patients that did not respond to treatment, and 46% of iNPH patients that were initially responsive to shunting. The most common cause of dementia was Alzheimer's disease (n = 94, 36%), followed by vascular dementia (n = 68, 26%). One-half of patients with enlarged ventricles and clinically suspected NPH were not shunted after intraventricular pressure monitoring. Dementia caused by various neurodegenerative diseases was frequently seen in patients with ventricular enlargement. Thus, careful diagnostic evaluation in collaboration with neurologists and neurosurgeons is emphasized.

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

    PubMed

    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

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

    PubMed

    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 < 0.01, voxel size > 40). The volume of right middle frontal gyrus reduced significantly (p < 0.01). The FA and ADC of 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.

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

    PubMed

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

    2017-03-17

    In the past 2 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 causes 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 to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD. © 2017 American Heart Association, Inc.

  6. Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals.

    PubMed

    Nakamoto, Beau K; Jahanshad, Neda; McMurtray, Aaron; Kallianpur, Kalpana J; Chow, Dominic C; Valcour, Victor G; Paul, Robert H; Marotz, Liron; Thompson, Paul M; Shikuma, Cecilia M

    2012-08-01

    HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.

  7. Electrocardiographic abnormalities in amateur male marathon runners.

    PubMed

    Kaleta, Anna M; Lewicka, Ewa; Dąbrowska-Kugacka, Alicja; Lewicka-Potocka, Zuzanna; Wabich, Elżbieta; Szerszyńska, Anna; Dyda, Julia; Sobolewski, Jakub; Koenner, Jakub; Raczak, Grzegorz

    2018-06-18

    Sports activity has become extremely popular among amateurs. Electrocardiography is a useful tool in screening for cardiac pathologies in athletes; however, there is little data on electrocardiographic abnormalities in the group of amateur athletes. The aim of this study was to analyze the abnormalities in resting and exercise electrocardiograms (ECGs) in a group of amateur athletes, and try to determine whether the criteria applied for the general population or for athletes' ECGs should be implemented in this group. In 40 amateur male marathon runners, 3 consecutive 12-lead ECGs were performed: 2-3 weeks before (stage 1), just after the run (stage 2) and 2-3 weeks after the marathon (stage 3). Resting (stage 1) and exercise (stage 2) ECGs were analyzed following the refined criteria for the assessment of athlete's ECG (changes classified as training-related, borderline or training-unrelated). In resting ECGs, at least 1 abnormality was found in 92.5% of the subjects and the most common was sinus bradycardia (62.5%). In post-exercise ECGs, at least 1 abnormality was present in 77.5% of the subjects and the most common was right atrium enlargement (RAE) (42.5%). Training-related ECG variants were more frequent at rest (82.5% vs 42.5%; p = 0.0008), while borderline variants - after the run (22.5% vs 57.5%; p = 0.0004). Training-unrelated abnormalities were found in 15% and 10% of the subjects, respectively (p-value - nonsignificant), and the most common was T-wave inversion. Even if the refined criteria rather than the criteria used for normal sedentary population were applied, the vast majority of amateur runners showed at least 1 abnormality in resting ECGs, which were mainly training-related variants. However, at rest, in 15% of the subjects, pathologic training-unrelated abnormalities were found. The most frequent post-exercise abnormality was right atrial enlargement. General electrocardiographic screening in amateur athletes should be taken into consideration.

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

    PubMed

    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.

  9. Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

    PubMed

    Ponz, Aurélie; Khatami, Ramin; Poryazova, Rositsa; Werth, Esther; Boesiger, Peter; Bassetti, Claudio L; Schwartz, Sophie

    2010-02-01

    Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.

  10. Co-localisation of abnormal brain structure and function in specific language impairment

    PubMed Central

    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 frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

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

    PubMed

    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.

  12. Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities.

    PubMed

    Matricardi, Sara; Spalice, Alberto; Salpietro, Vincenzo; Di Rosa, Gabriella; Balistreri, Maria Cristina; Grosso, Salvatore; Parisi, Pasquale; Elia, Maurizio; Striano, Pasquale; Accorsi, Patrizia; Cusmai, Raffaella; Specchio, Nicola; Coppola, Giangennaro; Savasta, Salvatore; Carotenuto, Marco; Tozzi, Elisabetta; Ferrara, Pietro; Ruggieri, Martino; Verrotti, Alberto

    2016-09-01

    This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non-specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    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.

  14. [X-ray computed tomographic abnormalities in schizophrenia. Trial of relationship with clinical data].

    PubMed

    D'Amato, T; Rochet, T; Dalery, J; Chauchat, J H; Terra, J L; Arteaga, C; Marie-Cardine, M

    1992-01-01

    Computerized tomography (CT-scan) studies in schizophrenia revealed that some patients have neuromorphological abnormalities. The structural changes consist mainly in lateral and third ventricle enlargement, and in cortical atrophy. The present study evaluates these three changes in 42 schizophrenics aged 18 to 50, compared to 24 healthy controls. Diagnosis were established from information gathered by personal interview with the SADS-LA. Clinical sub-types were evaluated according to the DSM III-R criteria. Moreover, detailed symptoms were rated according to the Positive And Negative Syndrome Scale (PANSS). CT scans were recorded in floppy disks and blindly analyzed. Schizophrenics shown significant higher mean size of lateral and third ventricles, and higher mean anterior cortical atrophy than healthy subjects. Significant differences were also found between subtypes, with more marked abnormalities in the disorganized group. The relationship between brain abnormalities and clinical symptoms recorded with the PANSS, were analysed using Pearson correlates. Positive correlations concerned mainly negative symptoms like blunted affect, emotional withdrawal, difficulties in abstract thinking, passive apathetic social withdrawal and lack of spontaneity of conversation. Positive correlations are also observed with some symptoms classified with the PANSS in the General Psychopathology scale such as mannerism and disorientation. Negative correlation concerned most of PANSS positive symptoms.

  15. The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia.

    PubMed

    Matsumoto, Mitsuyuki; Straub, Richard E; Marenco, Stefano; Nicodemus, Kristin K; Matsumoto, Shun-Ichiro; Fujikawa, Akihiko; Miyoshi, Sosuke; Shobo, Miwako; Takahashi, Shinji; Yarimizu, Junko; Yuri, Masatoshi; Hiramoto, Masashi; Morita, Shuji; Yokota, Hiroyuki; Sasayama, Takeshi; Terai, Kazuhiro; Yoshino, Masayasu; Miyake, Akira; Callicott, Joseph H; Egan, Michael F; Meyer-Lindenberg, Andreas; Kempf, Lucas; Honea, Robyn; Vakkalanka, Radha Krishna; Takasaki, Jun; Kamohara, Masazumi; Soga, Takatoshi; Hiyama, Hideki; Ishii, Hiroyuki; Matsuo, Ayako; Nishimura, Shintaro; Matsuoka, Nobuya; Kobori, Masato; Matsushime, Hitoshi; Katoh, Masao; Furuichi, Kiyoshi; Weinberger, Daniel R

    2008-04-22

    The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3' UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy.

  16. Cat-scratch disease. Subtle vertebral bone marrow abnormalities demonstrated by MR imaging and radionuclide bone scan.

    PubMed

    Wilson, J D; Castillo, M

    1995-01-01

    Cat-scratch disease (CSD) is a benign, self-limited cause of lymphadenitis occurring mainly in children and young adults. Its etiology is a delicate, small gram-negative pleomorphic bacillus. Less common manifestations of CSD are seen in 5% of patients and include Parinaud's oculoglandular syndrome (with enlargement of the preauricular nodes), parotid gland enlargement, encephalitis, radiculopathy, pneumonitis, erythema nodosum, thrombocytopenia, and lytic bone lesions. We describe a patient in whom magnetic resonance imaging initially detected subtle vertebral bone marrow abnormalities that correlated with the site of abnormality on a subsequent radionuclide bone scan.

  17. Co-localisation of abnormal brain structure and function in specific language impairment.

    PubMed

    Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

    2012-03-01

    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 frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Cullen's sign and massive ovarian enlargement secondary to primary hypothyroidism in a patient with a normal FSH receptor

    PubMed Central

    Sultan, A; Velaga, M R; Fleet, M; Cheetham, T

    2006-01-01

    Ovarian hyperstimulation is a recognised complication of longstanding hypothyroidism. A 12 year old girl with atrophic thyroiditis who presented with abdominal pain and distension is reported. She was noted to have bruising in the vicinity of the umbilicus (Cullen's sign). She had pronounced ovarian enlargement on ultrasonography and it was hypothesised that this profound phenotype might reflect an abnormal FSH receptor. However sequencing of the FSH receptor was normal. The ovarian enlargement resolved with thyroxine replacement. Physicians and surgeons should consider longstanding hypothyroidism in patients presenting with Cullen's sign. PMID:16714722

  19. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder.

    PubMed

    Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G

    2013-09-01

    resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.

  20. The impact of substance use on brain structure in people at high risk of developing schizophrenia.

    PubMed

    Welch, Killian A; McIntosh, Andrew M; Job, Dominic E; Whalley, Heather C; Moorhead, Thomas W; Hall, Jeremy; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

    2011-09-01

    Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

  1. Detection of eviscerated poultry spleen enlargement by machine vision

    NASA Astrophysics Data System (ADS)

    Tao, Yang; Shao, June J.; Skeeles, John K.; Chen, Yud-Ren

    1999-01-01

    The size of a poultry spleen is an indication of whether the bird is wholesomeness or has a virus-related disease. This study explored the possibility of detecting poultry spleen enlargement with a computer imaging system to assist human inspectors in food safety inspections. Images of 45-day-old hybrid turkey internal viscera were taken using fluorescent and UV lighting systems. Image processing algorithms including linear transformation, morphological operations, and statistical analyses were developed to distinguish the spleen from its surroundings and then to detect abnormal spleens. Experimental results demonstrated that the imaging method could effectively distinguish spleens from other organ and intestine. Based on a total sample of 57 birds, the classification rates were 92% from a self-test set, and 95% from an independent test set for the correct detection of normal and abnormal birds. The methodology indicated the feasibility of using automated machine vision systems in the future to inspect internal organs and check the wholesomeness of poultry carcasses.

  2. Structural and Perfusion Abnormalities of Brain on MRI and Technetium-99m-ECD SPECT in Children With Cerebral Palsy: A Comparative Study.

    PubMed

    Rana, Kamer Singh; Narwal, Varun; Chauhan, Lokesh; Singh, Giriraj; Sharma, Monica; Chauhan, Suneel

    2016-04-01

    Cerebral palsy has traditionally been associated with hypoxic ischemic brain damage. This study was undertaken to demonstrate structural and perfusion brain abnormalities. Fifty-six children diagnosed clinically as having cerebral palsy were studied between 1 to 14 years of age and were subjected to 3 Tesla magnetic resonance imaging (MRI). Brain and Technetium-99m-ECD brain single-photon emission computed tomography (SPECT) scan. Male to female ratio was 1.8:1 with a mean age of 4.16 ± 2.274 years. Spastic cerebral palsy was the most common type, observed in 91%. Birth asphyxia was the most common etiology (69.6%). White matter changes (73.2%) such as periventricular leukomalacia and corpus callosal thinning were the most common findings on MRI. On SPECT all cases except one revealed perfusion impairments in different regions of brain. MRI is more sensitive in detecting white matter changes, whereas SPECT is better in detecting cortical and subcortical gray matter abnormalities of perfusion. © The Author(s) 2015.

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

    PubMed

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

    2017-10-13

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

  4. Painful unilateral temporalis muscle enlargement: reactive masticatory muscle hypertrophy.

    PubMed

    Katsetos, Christos D; Bianchi, Michael A; Jaffery, Fizza; Koutzaki, Sirma; Zarella, Mark; Slater, Robert

    2014-06-01

    An instance of isolated unilateral temporalis muscle hypertrophy (reactive masticatory muscle hypertrophy with fiber type 1 predominance) confirmed by muscle biopsy with histochemical fiber typing and image analysis in a 62 year-old man is reported. The patient presented with bruxism and a painful swelling of the temple. Absence of asymmetry or other abnormalities of the craniofacial skeleton was confirmed by magnetic resonance imaging and cephalometric analyses. The patient achieved symptomatic improvement only after undergoing botulinum toxin injections. Muscle biopsy is key in the diagnosis of reactive masticatory muscle hypertrophy and its distinction from masticatory muscle myopathy (hypertrophic branchial myopathy) and other non-reactive causes of painful asymmetric temporalis muscle enlargement.

  5. Abnormal Functional Brain Asymmetry in Depression: Evidence of Biologic Commonality Between Major Depression and Dysthymia

    PubMed Central

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

    2012-01-01

    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. PMID:22397909

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

    PubMed

    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.

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

    PubMed

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

    2016-01-01

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

  8. Dyslexic brain activation abnormalities in deep and shallow orthographies: A meta‐analysis of 28 functional neuroimaging studies

    PubMed Central

    Martin, Anna; Kronbichler, Martin

    2016-01-01

    Abstract We used coordinate‐based meta‐analysis to objectively quantify commonalities and differences of dyslexic functional brain abnormalities between alphabetic languages differing in orthographic depth. Specifically, we compared foci of under‐ and overactivation in dyslexic readers relative to nonimpaired readers reported in 14 studies in deep orthographies (DO: English) and in 14 studies in shallow orthographies (SO: Dutch, German, Italian, Swedish). The separate meta‐analyses of the two sets of studies showed universal reading‐related dyslexic underactivation in the left occipitotemporal cortex (including the visual word form area (VWFA)). The direct statistical comparison revealed higher convergence of underactivation for DO compared with SO in bilateral inferior parietal regions, but this abnormality disappeared when foci resulting from stronger dyslexic task‐negative activation (i.e., deactivation relative to baseline) were excluded. Higher convergence of underactivation for DO compared with SO was further identified in the left inferior frontal gyrus (IFG) pars triangularis, left precuneus, and right superior temporal gyrus, together with higher convergence of overactivation in the left anterior insula. Higher convergence of underactivation for SO compared with DO was found in the left fusiform gyrus, left temporoparietal cortex, left IFG pars orbitalis, and left frontal operculum, together with higher convergence of overactivation in the left precentral gyrus. Taken together, the findings support the notion of a biological unity of dyslexia, with additional orthography‐specific abnormalities and presumably different compensatory mechanisms. The results are discussed in relation to current functional neuroanatomical models of developmental dyslexia. Hum Brain Mapp 37:2676–2699, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061464

  9. Abnormal brain processing of affective and sensory pain descriptors in chronic pain patients.

    PubMed

    Sitges, Carolina; García-Herrera, Manuel; Pericás, Miquel; Collado, Dolores; Truyols, Magdalena; Montoya, Pedro

    2007-12-01

    Previous research has suggested that chronic pain patients might be particularly vulnerable to the effects of negative mood during information processing. However, there is little evidence for abnormal brain processing of affective and sensory pain-related information in chronic pain. Behavioral and brain responses, to pain descriptors and pleasant words, were examined in chronic pain patients and healthy controls during a self-endorsement task. Eighteen patients with fibromyalgia (FM), 18 patients with chronic musculoskeletal pain due to identifiable physical injury (MSK), and 16 healthy controls were asked to decide whether word targets described their current or past experience of pain. The number of self-endorsed words, elapsed time to endorse the words, and event-related potentials (ERPs) elicited by words, were recorded. Data revealed that chronic pain patients used more affective and sensory pain descriptors, and were slower in responding to self-endorsed pain descriptors than to pleasant words. In addition, it was found that affective pain descriptors elicited significantly more enhanced positive ERP amplitudes than pleasant words in MSK pain patients; whereas sensory pain descriptors elicited greater positive ERP amplitudes than affective pain words in healthy controls. These data support the notion of abnormal information processing in chronic pain patients, which might be characterized by a lack of dissociation between sensory and affective components of pain-related information, and by an exaggerated rumination over word meaning during the encoding of self-referent information about pain.

  10. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    PubMed

    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

  11. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    PubMed Central

    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

  12. Gestational Age is Dimensionally Associated with Structural Brain Network Abnormalities Across Development.

    PubMed

    Nassar, Rula; Kaczkurkin, Antonia N; Xia, Cedric Huchuan; Sotiras, Aristeidis; Pehlivanova, Marieta; Moore, Tyler M; Garcia de La Garza, Angel; Roalf, David R; Rosen, Adon F G; Lorch, Scott A; Ruparel, Kosha; Shinohara, Russell T; Davatzikos, Christos; Gur, Ruben C; Gur, Raquel E; Satterthwaite, Theodore D

    2018-04-21

    Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later). Using a previously-validated factor analysis, cognitive performance was assessed in three domains: (1) executive function and complex reasoning, (2) social cognition, and (3) episodic memory. All participants completed T1-weighted neuroimaging at 3 T to measure brain volume. Structural covariance networks were delineated using non-negative matrix factorization, an advanced multivariate analysis technique. Lower gestational age was associated with both deficits in executive function and reduced volume within 11 of 26 structural covariance networks, which included orbitofrontal, temporal, and parietal cortices as well as subcortical regions including the hippocampus. Notably, the relationship between lower gestational age and executive dysfunction was accounted for in part by structural network deficits. Together, these findings emphasize the durable impact of prematurity on cognition and brain structure, which persists across development.

  13. Abnormal hippocampal shape in offenders with psychopathy.

    PubMed

    Boccardi, Marina; Ganzola, Rossana; Rossi, Roberta; Sabattoli, Francesca; Laakso, Mikko P; Repo-Tiihonen, Eila; Vaurio, Olli; Könönen, Mervi; Aronen, Hannu J; Thompson, Paul M; Frisoni, Giovanni B; Tiihonen, Jari

    2010-03-01

    Posterior hippocampal volumes correlate negatively with the severity of psychopathy, but local morphological features are unknown. The aim of this study was to investigate hippocampal morphology in habitually violent offenders having psychopathy. Manual tracings of hippocampi from magnetic resonance images of 26 offenders (age: 32.5 +/- 8.4), with different degrees of psychopathy (12 high, 14 medium psychopathy based on the Psychopathy Checklist Revised), and 25 healthy controls (age: 34.6 +/- 10.8) were used for statistical modelling of local changes with a surface-based radial distance mapping method. Both offenders and controls had similar hippocampal volume and asymmetry ratios. Local analysis showed that the high psychopathy group had a significant depression along the longitudinal hippocampal axis, on both the dorsal and ventral aspects, when compared with the healthy controls and the medium psychopathy group. The opposite comparison revealed abnormal enlargement of the lateral borders in both the right and left hippocampi of both high and medium psychopathy groups versus controls, throughout CA1, CA2-3 and the subicular regions. These enlargement and reduction effects survived statistical correction for multiple comparisons in the main contrast (26 offenders vs. 25 controls) and in most subgroup comparisons. A statistical check excluded a possible confounding effect from amphetamine and polysubstance abuse. These results indicate that habitually violent offenders exhibit a specific abnormal hippocampal morphology, in the absence of total gray matter volume changes, that may relate to different autonomic modulation and abnormal fear-conditioning. 2009 Wiley-Liss, Inc.

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  15. Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia.

    PubMed

    Hadar, R; Bikovski, L; Soto-Montenegro, M L; Schimke, J; Maier, P; Ewing, S; Voget, M; Wieske, F; Götz, T; Desco, M; Hamani, C; Pascau, J; Weiner, I; Winter, C

    2018-04-01

    The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.

  16. Enlarged Heart

    MedlinePlus

    ... rheumatic fever, a heart defect, infections (infectious endocarditis), connective tissue disorders, certain medications or radiation treatments for cancer, your heart may enlarge. Disease of the heart ...

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

    PubMed

    El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

    2016-01-01

    Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. © 2015 Wiley Periodicals, Inc.

  20. Larger Brains in Medication Naive High-Functioning Subjects with Pervasive Developmental Disorder

    ERIC Educational Resources Information Center

    Palmen, Saskia J. M. C.; Pol, Hilleke E. Hulshoff; Kemner, Chantal; Schnack, Hugo G.; Janssen, Joost; Kahn, Rene S.; van Engeland, Herman

    2004-01-01

    Background: Are brain volumes of individuals with Pervasive Developmental Disorder (PDD) still enlarged in adolescence and adulthood, and if so, is this enlargement confined to the gray and/or the white matter and is it global or more prominent in specific brain regions. Methods: Brain MRI scans were made of 21 adolescents with PDD and 21 closely…

  1. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

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

    PubMed Central

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

    2017-01-01

    Objective 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. Methods 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. Results 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). Conclusion 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. PMID:28243104

  3. Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin.

    PubMed

    Welch, Martha G; Welch-Horan, Thomas B; Anwar, Muhammad; Anwar, Nargis; Ludwig, Robert J; Ruggiero, David A

    2005-01-01

    Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.

  4. Cranial mononeuropathy III

    MedlinePlus

    ... is one of the cranial nerves that control eye movement. Causes may include: Brain aneurysm Infections Abnormal blood ... show: Enlarged (dilated) pupil of the affected eye Eye movement abnormalities Eyes that are not aligned Your health ...

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

    PubMed

    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.

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

    PubMed

    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 (p<0.001). Using GQI, we found decreases in diffusion anisotropy in the superior longitudinal fasciculus and increases in diffusion probability distribution in the frontal lobe among subjects with MDD (p<0.01). In GTA and NBS analyses, we found several disruptions in connectivity among subjects with MDD, particularly in the frontal lobes (p<0.05). In addition, structural alterations were correlated with depressive symptom severity (p<0.01). Small sample size; the cross-sectional design did not allow us to observe treatment effects in the MDD participants. Our results provide further evidence indicating that MDD may be conceptualized as a brain disorder with abnormal circuit structure and

  7. Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

    PubMed Central

    Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat; Yonekawa, Sayuri; FitzGibbon, Edmond J; Mankodi, Ami; Vanderver, Adeline; Schindler, Alice B; Toro, Camilo; Gahl, William A; Mahuran, Don J; Blackstone, Craig; Pierson, Tyler Mark

    2014-01-01

    Objective Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism. Methods We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26−/− mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. PMID:24999486

  8. Brain functional network abnormality extends beyond the sensorimotor network in brachial plexus injury patients.

    PubMed

    Feng, Jun-Tao; Liu, Han-Qiu; Hua, Xu-Yun; Gu, Yu-Dong; Xu, Jian-Guang; Xu, Wen-Dong

    2016-12-01

    Brachial plexus injury (BPI) is a type of severe peripheral nerve trauma that leads to central remodeling in the brain, as revealed by functional MRI analysis. However, previously reported remodeling is mostly restricted to sensorimotor areas of the brain. Whether this disturbance in the sensorimotor network leads to larger-scale functional remodeling remains unknown. We sought to explore the higher-level brain functional abnormality pattern of BPI patients from a large-scale network function connectivity dimension in 15 right-handed BPI patients. Resting-state functional MRI data were collected and analyzed using independent component analysis methods. Five components of interest were recognized and compared between patients and healthy subjects. Patients showed significantly altered brain local functional activities in the bilateral fronto-parietal network (FPN), sensorimotor network (SMN), and executive-control network (ECN) compared with healthy subjects. Moreover, functional connectivity between SMN and ECN were significantly less in patients compared with healthy subjects, and connectivity strength between ECN and SMN was negatively correlated with patients' residual function of the affected limb. Functional connectivity between SMN and right FPN were also significantly less than in controls, although connectivity between ECN and default mode network (DMN) was greater than in controls. These data suggested that brain functional disturbance in BPI patients extends beyond the sensorimotor network and cascades serial remodeling in the brain, which significantly correlates with residual hand function of the paralyzed limb. Furthermore, functional remodeling in these higher-level functional networks may lead to cognitive alterations in complex tasks.

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

    PubMed

    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.

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

    PubMed

    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.

  11. Abnormal brain synchrony in Down Syndrome☆

    PubMed Central

    Anderson, Jeffrey S.; Nielsen, Jared A.; Ferguson, Michael A.; Burback, Melissa C.; Cox, Elizabeth T.; Dai, Li; Gerig, Guido; Edgin, Jamie O.; Korenberg, Julie R.

    2013-01-01

    Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID:24179822

  12. Machine learning based brain tumour segmentation on limited data using local texture and abnormality.

    PubMed

    Bonte, Stijn; Goethals, Ingeborg; Van Holen, Roel

    2018-05-07

    Brain tumour segmentation in medical images is a very challenging task due to the large variety in tumour shape, position, appearance, scanning modalities and scanning parameters. Most existing segmentation algorithms use information from four different MRI-sequences, but since this is often not available, there is need for a method able to delineate the different tumour tissues based on a minimal amount of data. We present a novel approach using a Random Forests model combining voxelwise texture and abnormality features on a contrast-enhanced T1 and FLAIR MRI. We transform the two scans into 275 feature maps. A random forest model next calculates the probability to belong to 4 tumour classes or 5 normal classes. Afterwards, a dedicated voxel clustering algorithm provides the final tumour segmentation. We trained our method on the BraTS 2013 database and validated it on the larger BraTS 2017 dataset. We achieve median Dice scores of 40.9% (low-grade glioma) and 75.0% (high-grade glioma) to delineate the active tumour, and 68.4%/80.1% for the total abnormal region including edema. Our fully automated brain tumour segmentation algorithm is able to delineate contrast enhancing tissue and oedema with high accuracy based only on post-contrast T1-weighted and FLAIR MRI, whereas for non-enhancing tumour tissue and necrosis only moderate results are obtained. This makes the method especially suitable for high-grade glioma. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation.

    PubMed

    Eccles, J A; Garfinkel, S N; Harrison, N A; Ward, J; Taylor, R E; Bewley, A P; Critchley, H D

    2015-10-01

    Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure.

    PubMed

    Knirsch, Walter; Mayer, Kristina Nadine; Scheer, Ianina; Tuura, Ruth; Schranz, Dietmar; Hahn, Andreas; Wetterling, Kristina; Beck, Ingrid; Latal, Beatrice; Reich, Bettina

    2017-04-01

    Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities. Little is known about the further evolution of cerebral abnormalities until Fontan procedure. Between August 2012 and July 2015, we conducted a prospective cross-sectional two centre study using cerebral magnetic resonance imaging (MRI) and neuro-developmental outcome assessed by the Bayley-III. Forty-seven children (31 male) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome (25) or other single ventricle (22). Cerebral MRI was abnormal in 17 patients (36.2%) including liquor space enlargements (10), small grey (9) and minimal white (5) matter injuries. Eight of 17 individuals had combined lesions. Median (range) cognitive composite score (CCS) (100, 65-120) and motor composite score (MCS) (97, 55-124) were comparable to the reference data, while language composite score (LCS) (97, 68-124) was significantly lower ( P  = 0.040). Liquor space enlargement was associated with poorer performance on all Bayley-III subscores (CCS: P  = 0.02; LCS: P  = 0.002; MCS: P  = 0.013). The number of re-operations [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.3] ( P  = 0.03) and re-interventions (OR 2.1, 95% CI 1.1-3.8) ( P  = 0.03) was associated with a higher rate of overall MRI abnormalities. Cerebral MRI abnormalities occur in more than one third of children with single ventricle, while the neuro-developmental status is less severely affected before Fontan procedure. Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status, warranting further studies to determine aetiology and further evolution until school-age. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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

    PubMed Central

    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

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

    PubMed

    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

    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. 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. 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. The present results may be limited to the methods applied during preprocessing and network construction. 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.

  17. No evidence of early head circumference enlargements in children later diagnosed with autism in Israel.

    PubMed

    Dinstein, Ilan; Haar, Shlomi; Atsmon, Shir; Schtaerman, Hen

    2017-01-01

    Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder. We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy. The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life. These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population

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

    PubMed

    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.

  19. Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

    PubMed Central

    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

  20. Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

    PubMed

    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.

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

    PubMed

    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.

  2. Renal Epithelial Cyst Formation and Enlargement in vitro: Dependence on cAMP

    NASA Astrophysics Data System (ADS)

    Mangoo-Karim, Roberto; Uchic, Marie; Lechene, Claude; Grantham, Jared J.

    1989-08-01

    Cysts, a common abnormality of kidneys, are collections of urine-like fluid enclosed by a continuous layer of epithelial cells. Renal cysts derive from nephrons and collecting ducts and progressively enlarge as a consequence of epithelial proliferation and transepithelial fluid secretion. The initiation of cyst formation and the factors that control cyst enlargement are unknown. We used an in vitro model of renal cysts to explore the role of the cAMP signal transduction system in the formation and expansion of cysts. MDCK cells, cultured in hydrated-collagen gel, produced polarized monolayered epithelial cysts when intracellular cAMP was increased by prostaglandin E1, arginine vasopressin, cholera toxin, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate. All agonists were potentiated by 3-isobutyl-1-methylxanthine, a nucleotide phosphodiesterase inhibitor. The cell proliferation component of cyst enlargement was accelerated by cAMP agonists, as shown by the increased growth of MDCK cells in subconfluent monolayers. The fluid secretion component, reflected by the transepithelial movement of fluid across polarized monolayers of MDCK cells grown on permeable supports, was stimulated by cAMP agonists in the basolateral medium. Chloride levels were higher in the cyst fluid and the secreted fluid than in the bathing medium. We conclude that the development of MDCK cysts is dependent on cAMP. This signal transduction system may be an important modulator of epithelial cell proliferation and transepithelial fluid secretion in the kidney.

  3. Ultrasonographic identification of nerve pathology in neuralgic amyotrophy: Enlargement, constriction, fascicular entwinement, and torsion.

    PubMed

    Arányi, Zsuzsanna; Csillik, Anita; Dévay, Katalin; Rosero, Maja; Barsi, Péter; Böhm, Josef; Schelle, Thomas

    2015-10-01

    The aim of this study was to characterize the ultrasonographic findings on nerves in neuralgic amyotrophy. Fourteen patients with neuralgic amyotrophy were examined using high-resolution ultrasound. Four types of abnormalities were found: (1) focal or diffuse nerve/fascicle enlargement (57%); (2) incomplete nerve constriction (36%); (3) complete nerve constriction with torsion (50%; hourglass-like appearance); and (4) fascicular entwinement (28%). Torsions were confirmed intraoperatively and were seen on the radial nerve in 85% of patients. A significant correlation was found between no spontaneous recovery of nerve function and constriction/torsion/fascicular entwinement (P = 0.007). Ultrasonographic nerve pathology in neuralgic amyotrophy varies in order of severity from nerve enlargement to constriction to nerve torsion, with treatment ranging from conservative to surgical. We postulate that the constriction caused by inflammation is the precursor of torsion and that development of nerve torsion is facilitated by the rotational movements of limbs. © 2015 Wiley Periodicals, Inc.

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

    PubMed

    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.

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

    PubMed

    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.

  6. Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use.

    PubMed

    Mata, Ignacio; Perez-Iglesias, Rocio; Roiz-Santiañez, Roberto; Tordesillas-Gutierrez, Diana; Pazos, Angel; Gutierrez, Agustin; Vazquez-Barquero, Jose Luis; Crespo-Facorro, Benedicto

    2010-03-04

    Although cannabis is the most widely used illicit drug in the world, the long-term effect of its use in the brain remains controversial. In order to determine whether adolescence and early-adulthood cannabis use is associated with gross volumetric and gyrification abnormalities in the brain, we set up a cross-sectional study using structural magnetic resonance imaging in a sample of general population subjects. Thirty cannabis-using subjects (mean age, 25.7 years; mean duration of regular use, 8.4 years, range: 3-21) with no history of polydrug use or neurologic/mental disorder and 44 non-using control subjects (mean age, 25.8 years) were included. Cannabis users showed bilaterally decreased concavity of the sulci and thinner sulci in the right frontal lobe. Among non-users, age was significantly correlated with decreased gyrification (i.e., less concave sulci and more convexe gyri) and decreased cortical thickness, supporting the notion of age-related gyrification changes. However, among cannabis users gyrification indices did not show significant dependency on age, age of regular cannabis use initiation, or cumulative exposure to cannabis. These results suggest that cannabis use in adolescence and early-adulthood might involve a premature alteration in cortical gyrification similar to what is normally observed at a later age, probably through disruption of normal neurodevelopment. 2009 Elsevier B.V. All rights reserved.

  7. Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

    PubMed

    Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2015-05-01

    Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

  8. Abnormal neural activity of brain regions in treatment-resistant and treatment-sensitive major depressive disorder: a resting-state fMRI study.

    PubMed

    Guo, Wen-bin; Liu, Feng; Chen, Jin-dong; Gao, Keming; Xue, Zhi-min; Xu, Xi-jia; Wu, Ren-rong; Tan, Chang-lian; Sun, Xue-li; Liu, Zhe-ning; Chen, Hua-fu; Zhao, Jing-ping

    2012-10-01

    Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions. Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study. ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively. Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Airport Performance and Construction Enlargement Activities

    NASA Astrophysics Data System (ADS)

    Hanun, Y.; Setiawan, M. I.; Kurniasih, N.; Hasyim, C.; Ahmar, A. S.

    2018-01-01

    The evaluation of transportation infrastructure project should consider the contribution towards infrastructure growth. This research aims to analyze the effect of Construction enlargement activities towards airport performance. This research is correlation study. The population includes 148 airports in Indonesia. By using total sampling, there were 148 sample airports. The result shows that the construction enlargement activities variable has relatively strong relationship to Airport Performance variable, while the adjusted R Square score shows the increasing construction enlargement activities that affected by the other factors aside from airport performance.

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

    PubMed Central

    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

  11. Pseudoangiomatous stromal hyperplasia causing massive breast enlargement

    PubMed Central

    Bourke, Anita Geraldine; Tiang, Stephen; Harvey, Nathan; McClure, Robert

    2015-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement. PMID:26475873

  12. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    ERIC Educational Resources Information Center

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  13. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  14. LIPID ABNORMALITIES IN SUCCINATE SEMIALDEHYDE DEHYDROGENASE (Aldh5a1−/−) DEFICIENT MOUSE BRAIN PROVIDE ADDITIONAL EVIDENCE FOR MYELIN ALTERATIONS

    PubMed Central

    Barcelo-Coblijn, G.; Murphy, E. J.; Mills, K.; Winchester, B.; Jakobs, C.; Snead, O.C.; Gibson, KM

    2007-01-01

    Earlier work from our laboratory provided evidence for myelin abnormalities (decreased quantities of proteins associated with myelin compaction, decreased sheath thickness) in cortex and hippocampus of Aldh5a1−/− mice, which have a complete ablation of the succinate semialdehyde dehydrogenase protein [1]. In the current report, we have extended these findings via comprehensive analysis of brain phospholipid fractions, including quantitation of fatty acids in individual phospholipid subclasses and estimation of hexose-ceramide in Aldh5a1−/− brain. In comparison to wild-type littermates (Aldh5a1+/+), we detected a 20% reduction in the ethanolamine glycerophospholipid content of Aldh5a1−/− mice, while other brain phospholipids (choline glycerophospholipid, phosphatidylserine and phosphatidylinositol) were within normal limits. Analysis of individual fatty acids in each of these fractions revealed consistent alterations in n-3 fatty acids, primarily increased 22:6n-3 levels (docosahexaenoic acid; DHA). In the phosphatidyl serine fraction there were marked increases in the proportions of polyunsaturated fatty acids with corresponding decreases of monounsaturated fatty acids. Interestingly, the levels of hexose-ceramide (glucosyl- and galactosylceramide, principal myelin cerebrosides) were decreased in Aldh5a1−/− brain tissue (one-tailed t test, p=0.0449). The current results suggest that lipid and myelin abnormalities in this animal may contribute to the pathophysiology. PMID:17300923

  15. Ultrastructural brain abnormalities and associated behavioral changes in mice after low-intensity blast exposure.

    PubMed

    Song, Hailong; Konan, Landry M; Cui, Jiankun; Johnson, Catherine E; Langenderfer, Martin; Grant, DeAna; Ndam, Tina; Simonyi, Agnes; White, Tommi; Demirci, Utkan; Mott, David R; Schwer, Doug; Hubler, Graham K; Cernak, Ibolja; DePalma, Ralph G; Gu, Zezong

    2018-07-16

    Explosive blast-induced mild traumatic brain injury (mTBI), a "signature wound" of recent military conflicts, commonly affects service members. While past blast injury studies have provided insights into TBI with moderate- to high-intensity explosions, the impact of primary low-intensity blast (LIB)-mediated pathobiology on neurological deficits requires further investigation. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a primary LIB injury murine model exposed to open field detonation of 350 g of high-energy explosive C4. We quantified ultrastructural and behavioral changes up to 30 days post blast injury (DPI). The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 PSI (46.6 kPa) at a 3-m distance from the center of the explosion, a positive phase duration of approximate 3.0 milliseconds (ms), a maximal impulse of 8.7 PSI × ms and a sharp rising time of 9 × 10 -3  ms, with no apparent impact/acceleration in exposed animals. Neuropathologically, myelinated axonal damage was observed in blast-exposed groups at 7 DPI. Using transmission electron microscopy, we observed and quantified myelin sheath defects and mitochondrial abnormalities at 7 and 30 DPI. Inverse correlations between blast intensities and neurobehavioral outcomes including motor activities, anxiety levels, nesting behavior, spatial learning and memory occurred. These observations uncover unique ultrastructural brain abnormalities and associated behavioral changes due to primary blast injury and provide key insights into its pathogenesis and potential treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

    PubMed

    Li, Yaqin; Cao, Jiqing; Chen, Menglong; Li, Jing; Sun, Yiming; Zhang, Yu; Zhu, Yuling; Wang, Liang; Zhang, Cheng

    2017-04-11

    Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells. TSC2 astrocytes had increased saturation density and higher proliferative activity. Moreover, the activity of the mTOR pathway was enhanced in pNSCs and induced in neurons and astrocytes. Thus, our results suggested that TSC2 heterozygosity caused neurological malformations in pNSCs, indicating that its heterozygosity might be sufficient for the development of neurological abnormalities in patients. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Dandy-Walker syndrome and chromosomal abnormalities.

    PubMed

    Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

    2007-12-01

    Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

  18. Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

    PubMed Central

    Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

    2011-01-01

    The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

  19. Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

    PubMed

    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 <45 mL/min/1.73 m 2 ) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in 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

  20. An improved FSL-FIRST pipeline for subcortical gray matter segmentation to study abnormal brain anatomy using quantitative susceptibility mapping (QSM).

    PubMed

    Feng, Xiang; Deistung, Andreas; Dwyer, Michael G; Hagemeier, Jesper; Polak, Paul; Lebenberg, Jessica; Frouin, Frédérique; Zivadinov, Robert; Reichenbach, Jürgen R; Schweser, Ferdinand

    2017-06-01

    Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T 1 -weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images. Consequently, such deviations from the average brain anatomy may introduce analysis bias in clinical studies, which may not always be obvious and potentially remain unidentified. To improve the segmentation of subcortical nuclei, we propose to use FIRST in combination with a special Hybrid image Contrast (HC) and Non-Linear (nl) registration module (HC-nlFIRST), where the hybrid image contrast is derived from T1w images and magnetic susceptibility maps to create subcortical contrast that is similar to that in the Montreal Neurological Institute (MNI) template. In our approach, a nonlinear registration replaces FIRST's default linear registration, yielding a more accurate alignment of the input data to the MNI template. We evaluated our method on 82 subjects with particularly abnormal brain anatomy, selected from a database of >2000 clinical cases. Qualitative and quantitative analyses revealed that HC-nlFIRST provides improved segmentation compared to the default FIRST method. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Abnormal brain activation in excoriation (skin-picking) disorder: evidence from an executive planning fMRI study

    PubMed Central

    Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R.; Grant, Jon E.

    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 planning task (Tower of London) during functional magnetic resonance imaging (fMRI). Activation during planning was compared between groups using region of interest and whole-brain permutation cluster approaches. Results The SPD group exhibited significant functional underactivation in a cluster 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. PMID:26159604

  2. DTI-measured white matter abnormalities in adolescents with Conduct Disorder

    PubMed Central

    Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

    2013-01-01

    Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter

  3. Severe gingival enlargement associated with aggressive periodontitis

    PubMed Central

    Padmanabhan, Shyam; Dwarakanath, C. D.

    2013-01-01

    Enlargement of the gingiva can be due to various causes. Most prevalent are the inflammatory type and drug-induced type of gingival hyperplasia. However, sever enlargement associated with an aggressive type of periodontitis is an infrequent finding. Reported here is a case of a female patient aged 18 years who presented with severe enlargement of the maxillary and mandibular gingiva. Examination revealed enlargement extending up to the incisal edge of all the teeth and also an associated generalized loss of attachment with radiographic evidence of reduced bone height resembling an aggressive type of periodontitis. There were no associated systemic signs and symptoms or any family history except that there was generalized vitiligo of the skin and oral mucous membrane. The case was treated by gross electrosection of the gingiva. PMID:23633785

  4. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  5. Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

    PubMed

    Li, Linling; Ji, Erni; Tang, Fei; Qiu, Yunhai; Han, Xue; Zhang, Shengli; Zhang, Zhiguo; Yang, Haichen

    2018-06-16

    Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years). Two emotional tasks were applied in this study: one used emotional pictures of everyday objects and scenes, and another used emotional facial expression pictures. The main findings were that BD on lithium showed increased fMRI activation in the right dorsal anterior cingulate cortex and bilateral lingual gyrus in response to the positive pictures relative to neutral pictures compared with BD on valproate and HC. Besides, no abnormal activation was observed in the amygdala. Limitations of this study comprise the small sample size and the cross-sectional design. Therefore, the results were suggestive of a different effect of lithium and valproate on brain activities during emotion processing but no causal role can be proposed. The enduring impairments in euthymic state could provide clues to the brain regions involved in the primary pathology of BD.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26796967

  7. Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

    PubMed

    Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

    1998-11-01

    Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

  8. Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

    PubMed

    Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

    2016-02-01

    This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect. © The Author(s) 2016.

  9. Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

    PubMed

    Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

    2016-11-01

    To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes.

    PubMed

    Mainz, Verena; Schulte-Rüther, Martin; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2012-01-01

    The neurobiological mechanisms of structural brain abnormalities in patients with anorexia nervosa (AN) remain poorly understood. In particular, little is known about the changes in and the recovery of gray matter (GM) volumes after weight gain and the relation to hormonal normalization in adolescent patients with AN. Nineteen female patients aged 12 to 17 years were assessed using magnetic resonance imaging at the time of admission to the hospital (T1) and after weight recovery (T2). Patients were compared with typically developing girls matched for age and intelligence quotient. Structural brain images were analyzed using a voxel-based morphometric approach. Circulating levels of cortisol and gonadotropins were assessed in blood samples. Compared with controls, patients with AN showed reduced GM in several brain regions along the cortical midline, reaching from the occipital cortex to the medial frontal areas. These GM reductions were mostly reversible at T1. Patients showed a GM increase from T1 to T2 along the cortical midline and in the occipital, temporal, parietal, and frontal lobes. GM increases at T2 correlated inversely with cortisol levels at T1 and positively with weight gain at T2. The strongest associations between regional GM increase and weight gain were found in the cerebellum. In addition, increases in GM volumes at T2 in the thalamus, hippocampus, and amygdala were associated with increases in follicle-stimulating hormone. Our data suggest that brain alterations in adolescents with acute AN are mostly reversible at T1 and that GM recovery in specific brain regions is associated with weight and hormonal normalization.

  11. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

    PubMed

    Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

    2016-06-01

    Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

  12. Assessment of electrocardiographic criteria of left atrial enlargement.

    PubMed

    Batra, Mahesh Kumar; Khan, Atif; Farooq, Fawad; Masood, Tariq; Karim, Musa

    2018-05-01

    Background Left atrial enlargement is considered to be a robust, strong, and widely acceptable indicator of cardiovascular outcomes. Echocardiography is the gold standard for measurement of left atrial size, but electrocardiography can be simple, cost-effective, and noninvasive in clinical practice. This study was undertaken to assess the diagnostic accuracy of an established electrocardiographic criterion for left atrial enlargement, taking 2-dimensional echocardiography as the gold-standard technique. Methods A cross-sectional study was conducted on 146 consecutively selected patients with the complaints of dyspnea and palpitation and with a murmur detected on clinical examination, from September 10, 2016 to February 10, 2017. Electrocardiography and echocardiography were performed in all patients. Patients with a negative P wave terminal force in lead V 1  > 40 ms·mm on electrocardiography or left atrial dimension > 40 mm on echocardiography were classified as having left atrial enlargement. Sensitivity and specificity were calculated to assess the diagnostic accuracy. Results Taking 2-dimensional echocardiography as the gold-standard technique, electrocardiography correctly diagnosed 68 patients as positive for left atrial enlargement and 12 as negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of electrocardiography for left atrial enlargement were 54.4%, 57.1%, 88.3%, 17.4%, and 54.8%, respectively. Conclusion The electrocardiogram appears to be a reasonable indicator of left atrial enlargement. In case of nonavailability of echocardiography, electrocardiography can be used for diagnosis of left atrial enlargement.

  13. Abnormal regional cerebral blood flow in childhood autism.

    PubMed

    Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

    2000-09-01

    Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

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

    PubMed

    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 (p<0.05, cluster-corrected) volume decrease of the anterior cingulate cortex (ACC) was found in MDD compared to HC, as opposed to volume decreases of the amygdala in BPD compared to both HC and MDD. Sensitivity and specificity of regional gray matter volume for a diagnosis of MDD were modest to fair. Amygdala volume was related to depressive symptoms across the entire patient sample. Potential limitations of this study include the modest sample size and the heterogeneous psychotropic drug treatment. ACC volume reduction is more pronounced in MDD with an intermediate degree of volume loss in BPD compared to HC. In contrast, amygdala volume loss is more pronounced in BPD compared to MDD, yet amygdala volume is associated with affective symptom expression in both disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia.

    PubMed

    Liu, Wenying Angela; Chen, She; Li, Zhizhong; Lee, Choong Heon; Mirzaa, Ghayda; Dobyns, William B; Ross, M Elizabeth; Zhang, Jiangyang; Shi, Song-Hai

    2018-06-01

    Proper organization and orderly mitosis of radial glial progenitors (RGPs) drive the formation of a laminated mammalian cortex in the correct size. However, the molecular underpinnings of the intricate process remain largely unclear. Here we show that RGP behavior and cortical development are controlled by temporally distinct actions of partitioning-defective 3 (PARD3) in concert with dynamic HIPPO signaling. RGPs lacking PARD3 exhibit developmental stage-dependent abnormal switches in division mode, resulting in an initial overproduction of RGPs located largely outside the ventricular zone at the expense of deep-layer neurons. Ectopically localized RGPs subsequently undergo accelerated and excessive neurogenesis, leading to the formation of an enlarged cortex with massive heterotopia and increased seizure susceptibility. Simultaneous removal of HIPPO pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) suppresses cortical enlargement and heterotopia formation. These results define a dynamic regulatory program of mammalian cortical development and highlight a progenitor origin of megalencephaly with ribbon heterotopia and epilepsy. © 2018 Liu et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Brain Aneurysm

    MedlinePlus

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  17. Biochemical abnormalities in neonatal seizures.

    PubMed

    Sood, Arvind; Grover, Neelam; Sharma, Roshan

    2003-03-01

    The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

  18. Enlarged squamous cell nuclei in cervical cytologic specimens from perimenopausal women ("PM Cells") : a cause of ASC overdiagnosis.

    PubMed

    Cibas, Edmund S; Browne, Tara-Jane; Bassichis, Michelle H Mantel; Lee, Kenneth R

    2005-07-01

    We studied the appropriateness of interpreting squamous cells with enlarged, smooth, bland nuclei in perimenopausal women ("PM cells") as atypical squamous cells (ASCs). Papanicolaou smears (Paps) from 100 women (40-55 years old) with a cytologic interpretation of ASC of undetermined significance (ASCUS) and human papillomavirus (HPV) testing or a biopsy within 6 months were reviewed by 2 observers without knowledge of the biopsy diagnosis or HPV results. Cases in which both reviewers agreed that the Paps were diagnosed more properly as "negative for intraepithelial lesion or malignancy" were compared with cases of "true ASCUS," using histologic squamous intraepithelial lesion and/or a positive high-risk HPV test as a positive outcome (abnormal follow-up). Of 100 cases, 28 were reclassified as benign by both observers. In 15 of these, the original ASCUS interpretation was based on cells with bland nuclear enlargement (2-3 times the area of intermediate cell nuclei), smooth nuclear membranes, and fine chromatin. Abnormal follow-up was identified in 1 (7%) of 15 benign cases but in 30 (42%) of 72 true ASCUS cases (P = .023). PM cells are a significant cause of ASC overdiagnosis in women 40 to 55 years old. Cervical Paps with cells no more atypical than these can be interpreted safely as negative for intraepithelial lesion or malignancy.

  19. Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States

    PubMed Central

    Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra; Beaunieux, Hélène; Eustache, Francis; Martinot, Jean-Luc; Reynaud, Michel; Martelli, Catherine; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V.

    2015-01-01

    Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS. PMID:26157376

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

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

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

    PubMed

    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.

  2. Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

    PubMed

    Elmaleh-Bergès, M; Baumann, C; Noël-Pétroff, N; Sekkal, A; Couloigner, V; Devriendt, K; Wilson, M; Marlin, S; Sebag, G; Pingault, V

    2013-01-01

    Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

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

    PubMed Central

    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

  4. Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

    PubMed Central

    Zhou, Joanne; Butler, Erin E.; Rose, Jessica

    2017-01-01

    Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP. PMID:28367118

  5. Excessive homozygosity identified by chromosomal microarray at a known GCDH mutation locus correlates with brain MRI abnormalities in an infant with glutaric aciduria.

    PubMed

    Peer-Zada, Abdul Ali; Al-Asmari, Ali M

    2017-08-01

    Herein, we report a conceptually novel clinical case highlighting the diagnostic implications of excessive homozygosity and its correlation with brain MRI abnormalities in an infant with GA1. The case also points a need for an extra amount of caution to be exercised when evaluating patients with "negative exomes."

  6. Scalable screen-size enlargement by multi-channel viewing-zone scanning holography.

    PubMed

    Takaki, Yasuhiro; Nakaoka, Mitsuki

    2016-08-08

    Viewing-zone scanning holographic displays can enlarge both the screen size and the viewing zone. However, limitations exist in the screen size enlargement process even if the viewing zone is effectively enlarged. This study proposes a multi-channel viewing-zone scanning holographic display comprising multiple projection systems and a planar scanner to enable the scalable enlargement of the screen size. Each projection system produces an enlarged image of the screen of a MEMS spatial light modulator. The multiple enlarged images produced by the multiple projection systems are seamlessly tiled on the planar scanner. This screen size enlargement process reduces the viewing zones of the projection systems, which are horizontally scanned by the planar scanner comprising a rotating off-axis lens and a vertical diffuser to enlarge the viewing zone. A screen size of 7.4 in. and a viewing-zone angle of 43.0° are demonstrated.

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

    PubMed

    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.

  8. Enlarged Adenoids (For Parents)

    MedlinePlus

    ... topic for: Parents Kids Teens Tonsils and Tonsillectomies Strep Throat Obstructive Sleep Apnea Preparing Your Child for Surgery ... the Operating Room? Snoring Tonsillitis All About Adenoids Strep Throat Enlarged Adenoids Tonsils and Tonsillectomies What's It Like ...

  9. Femoral tunnel enlargement after anatomic ACL reconstruction: a biological problem?

    PubMed

    Silva, Alcindo; Sampaio, Ricardo; Pinto, Elisabete

    2010-09-01

    Tunnel enlargement after anterior cruciate ligament (ACL) reconstruction may compromise revision surgery. The cause of this tunnel enlargement is not yet fully understood, but it is thought to be multifactorial, with biomechanical and biological factors playing a role. Tunnel enlargement has been described particularly in patients who underwent ACL reconstruction with hamstring tendons with extracortical fixation devices. The purpose of our study was to evaluate prospectively with magnetic resonance imaging (MRI) the changes in femoral tunnel diameter following arthroscopic anatomic ACL reconstruction with hamstring tendons. At 3-month post-op, all tunnels had enlarged compared to the diameter of the drill and most tunnels enlarged more in the midsection than at the aperture. In the posterolateral tunnels, the entrance increased 16% in diameter and the middle of the tunnel increased 30% in diameter. In the anteromedial femoral tunnels, the tunnels enlarged 14% at the aperture and 35% in the midsection. All femoral tunnels enlarged and most of them enlarged in a fusiform manner. The biological factors explain better our findings than the mechanical theory, although mechanical factors may play a role and the cortical bone at the entrance of the tunnel may modify the way tunnels respond to mechanical stress.

  10. Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism).

    PubMed

    Marin-Padilla, M; Marin-Padilla, T M

    1977-01-01

    Specific developmental malformations have been demonstrated in the occipital bone of two chondrodysplastic disorders (achondroplasia and thanatophoric dwarfism). Analysis of these malformations indicates that the occipital bone is primary affected in these disorders. In both cases, the endochondral-derived components of the occipital bone (the basioccipital, the two lateral parts, and the planum nuchale of the squama occipitalis) have failed to grow properly and are smaller and shorter than normal. On the other hand, the planum occipitalis of the squama, which derives from intramembranous ossification, is unaffected. In addition, the nature of these abnormalities indicates that the occipital synchondroses, together with the epiphyseal plates of other bones, are primarily affected in these two chondrodysplasias. The components of the occipital bone formed between the affected synchondroses failed to grow normally. The resulting malformation of the occipital bone is undoubtedly the cause of the shortening of the posterior cerebral fossa and of the considerable narrowing of the foramen magnum often described in these chondrodysplasias. It is postulated that growth disturbances between the affected occipital bone and the unaffected central nervous system results in the inadequacy of the posterior cerebral fossa and the foramen magnum to accommodate the growing brain. Consequently, compression of the brain at the posterior cerebral fossa or the foramen magnum levels could occur and thus lead to neurologic complications such as hydrocephalus and compression of the brain stem. It is suggested that the surgical removal of the fused posterior border of the lateral parts of the occipital bone (partial nuchalectomy) for the purpose of enlarging the narrow foramen magnum may be indicated in those chondrodysplastic children who develop these types of neurologic complications.

  11. An Examination of Brain Abnormalities and Mobility in Individuals with Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Fischer, Barbara L.; Bacher, Rhonda; Bendlin, Barbara B.; Birdsill, Alex C.; Ly, Martina; Hoscheidt, Siobhan M.; Chappell, Richard J.; Mahoney, Jane E.; Gleason, Carey E.

    2017-01-01

    Background: Mobility changes are concerning for elderly patients with cognitive decline. Given frail older individuals' vulnerability to injury, it is critical to identify contributors to limited mobility. Objective: To examine whether structural brain abnormalities, including reduced gray matter volume and white matter hyperintensities, would be associated with limited mobility among individuals with cognitive impairment, and to determine whether cognitive impairment would mediate this relationship. Methods: Thirty-four elderly individuals with mild cognitive impairment (MCI) and Alzheimer's disease underwent neuropsychological evaluation, mobility assessment, and structural brain neuroimaging. Linear regression was conducted with predictors including gray matter volume in six regions of interest (ROI) and white matter hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower gray matter volume in caudate nucleus was associated with slower speed on a functional mobility task. Higher cerebellar volume was also associated with slower functional mobility. White matter hyperintensity burden was not significantly associated with mobility. Conclusion: Our findings provide evidence for associations between subcortical gray matter volume and speed on a functional mobility task among cognitively impaired individuals. PMID:28424612

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

    PubMed

    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 (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.

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

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

    Johnson, M.A,; Pennock, J.M.; Bydder, G.M.

    1983-11-01

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

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

    PubMed

    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.

  15. Developmental vitamin D deficiency causes abnormal brain development.

    PubMed

    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

  16. 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.

    USGS Publications Warehouse

    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

  17. Effect of contrast leakage on the detection of abnormal brain tumor vasculature in high-grade glioma.

    PubMed

    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.

  18. Urea cycle disorders: brain MRI and neurological outcome.

    PubMed

    Bireley, William R; Van Hove, Johan L K; Gallagher, Renata C; Fenton, Laura Z

    2012-04-01

    Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe. The goal of this study was to correlate brain MRI abnormalities in urea cycle disorders with clinical neurological sequelae to evaluate whether MRI abnormalities can assist in guiding difficult treatment decisions. We performed a retrospective chart review of patients with urea cycle disorders and symptomatic hyperammonemia. Brain MRI images were reviewed for abnormalities that correlated with severity of clinical neurological sequelae. Our case series comprises six urea cycle disorder patients, five with ornithine transcarbamylase deficiency and one with citrullinemia type 1. The observed trend in distribution of brain MRI abnormalities as the severity of neurological sequelae increased was the peri-insular region first, extending into the frontal, parietal, temporal and, finally, the occipital lobes. There was thalamic restricted diffusion in three children with prolonged hyperammonemia. Prior to death, this site is typically reported to be spared in urea cycle disorders. The pattern and extent of brain MRI abnormalities correlate with clinical neurological outcome in our case series. This suggests that brain MRI abnormalities may assist in determining prognosis and helping clinicians with subsequent treatment decisions.

  19. Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

    PubMed Central

    Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

    2015-01-01

    Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

  20. Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.

    PubMed

    Haroutunian, Vahram; Davis, Kenneth L

    2007-08-01

    A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths.

  1. Noninvasive assessment of T-wave abnormalities on precordial electrocardiograms in middle-aged professional bicyclists

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

    Nishimura, T.; Kambara, H.; Chen, C.H.

    Six middle-aged, active, professional bicyclists with T-wave abnormalities on precordial ECGs were studied noninvasively. Twenty-five aged-matched bicyclists without T-wave abnormalities served as the control subjects. Increased voltage of SV1 + RV5 was demonstrated in all subjects. A 5-year follow-up study revealed that these abnormalities of T-wave inversion became more pronounced with age, except in one case. VCGs showed enlargement of anterior QRS loop and discordant T loop, in all cases. On echocardiography, thickness of both the interventricular septum and the left ventricular posterior wall, and left ventricular mass were significantly increased compared with the control group. 201Tl myocardial scintigraphy atmore » rest and during exercise revealed no regional perfusion defects of the tracer in either case. We conclude that: (1) T-wave abnormalities of precordial ECGs in six middle-aged athletes were progressive in nature; and (2) these electrocardiographic abnormalities seem to be related to left ventricular hypertrophy induced by steady and strenuous training rather than to coronary artery disease.« less

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

    PubMed Central

    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 (p<0.001 uncorrected) in the left 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

  3. Neurologic abnormalities in murderers.

    PubMed

    Blake, P Y; Pincus, J H; Buckner, C

    1995-09-01

    Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

  4. Use of Macrolane VRF 30 in emicircumferential penis enlargement.

    PubMed

    Sito, Giuseppe; Marlino, Sergio; Santorelli, Adriano

    2013-02-01

    Penis enlargement is increasingly in demand. Methods for penis enlargement can be classified into surgical, nonsurgical (filling), and mechanical. Each method has shown only relatively successful results. A new formulation of injectable, stabilized, hyaluronic acid (HA)-based, nonanimal gel is available that may have applications for this use. The authors propose a new technique for emicircumferential-injection filling of the penis and assess the safety and efficacy of this procedure compared with lipofilling. The authors retrospectively reviewed the charts of 83 patients who underwent penis enlargement with either their HA-injection technique or lipofilling between December 2007 and July 2011. Safety, efficacy, and patient satisfaction were assessed. The circumferential enlargement obtained from both techniques ranged from 3.2 to 4.5 cm, with a decrement during erection. In all patients, the increase in penis length ranged from 1.8 to 3.6 cm. No complications were seen in patients treated with HA, whereas 8 patients treated with lipofilling developed granuloma, and another experienced fat necrosis. The vast majority (n = 72) of patients reported being "very satisfied" with the results. The ideal technique for penis enlargement should be nonsurgical, with a satisfactory and predictable result, a low rate of complications, and long-term stability. Emicircumferential enlargement with HA filler meets these requirements. However, results have been durable but not definitive, and repeated treatment (with associated costs) is necessary.

  5. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  6. Brain Dysplasia Associated with Ciliary Dysfunction In Infants with Congenital Heart Disease

    PubMed Central

    Panigrahy, Ashok; Lee, Vincent; Ceschin, Rafael; Zuccoli, Giulio; Beluk, Nancy; Khalifa, Omar; Votava-Smith, Jodie K; DeBrunner, Mark; Munoz, Ricardo; Domnina, Yuliya; Morell, Victor; Wearden, Peter; De Toledo, Joan Sanchez; Devine, William; Zahid, Maliha; Lo, Cecilia W.

    2016-01-01

    Objective To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) Study design We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound and brain magnetic resonance imaging were obtained pre- and/or post-operatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. Results A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury, but was correlated with increased extra-axial CSF volume (p<0.001), delayed brain maturation (p<0.05), and a spectrum of subtle dysplasia including the hippocampus (p<0.0078) and olfactory bulb (p<0.034). Abnormal CM was associated with higher composite dysplasia score (p<0.001) and both were correlated with elevated pre-operative serum lactate (p <0.001). Conclusion Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks. PMID:27574995

  7. A newborn with unilateral limb enlargement.

    PubMed

    Sharma, Shanel; Maino, Anna P F; Husain, Shad M; Adams, Gill G W

    2012-03-01

    On routine neonatal examination, a newborn term male was noted to have unilateral enlargement of the right lower limb, loose thickened red skin over the palm and widening of all the fingers on the right hand. His body was pinker and warmer on the right side compared with the left and he had a right undescended testicle and hypoplastic scrotum. Radiological examination of the lower limbs demonstrated the enlargement of the soft tissue of the right lower limb compared to the left (Fig. 1). Therefore, the diagnosis was unclear from this constellation of findings and an ophthalmic assessment was requested.

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

    PubMed

    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 < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral 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.

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

    PubMed

    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.

  10. Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

    PubMed Central

    Pitel, Anne-Lise; Aupée, Anne-Marie; Chételat, Gaël; Mézenge, Florence; Beaunieux, Hélène; de la Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Desgranges, Béatrice

    2009-01-01

    Background Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. Methodology/Principal Findings Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. Conclusions/Significance These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker. PMID:19936229

  11. Job Enlargement: A Multidimensional Process

    ERIC Educational Resources Information Center

    Donaldson, Lex

    1975-01-01

    An evaluation study into the effects of a job enlargement exercise indicates that the expected increases in satisfaction associated with greater work variety, novelty, and felt use of abilities were achieved. (Author/MLF)

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

    PubMed

    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.

  13. Abnormal spontaneous brain activity is associated with impaired emotion and cognition in hyperthyroidism: A rs-fMRI study.

    PubMed

    Zhi, Mengmeng; Hou, Zhenghua; We, Qiong; Zhang, Yuqun; Li, Ling; Yuan, Yonggui

    2018-06-07

    Hyperthyroid patients undergo emotional and cognitive dysfunction. However, the neurological basis for it remains ambiguous. Amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were used to investigate abnormal spontaneous activity in hyperthyroidism for the first time. 29 hyperthyroid patients and 29 healthy controls (HC) received 3.0T magnetic resonance imaging (MRI) scans and neuropsychological assessments. Compared with HC, hyperthyroid patients showed decreased ALFF in left medial frontal gyrus (MeFG) and left posterior cingulate cortex (PCC). Hyperthyroidism group exhibited decreased ReHo in left MeFG. Within hyperthyroidism group, ALFF values in left MeFG were positively correlated with Hamilton Anxiety Rating Scale (HARS) Z-scores, but negatively correlated with processing speed Z-scores. Besides, ALFF values in left precuneus had a positive correlation with HARS Z-scores. As a result, abnormal brain spontaneous activity mainly in default mode network (DMN) implicated the neuro-pathological substrate of relevant emotional and cognitive dysfunction in hyperthyroid patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Trajectories of Early Brain Volume Development in Fragile X and Autism RH: Trajectory of Brain Volume in Fragile X

    PubMed Central

    Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

    2012-01-01

    Objective To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared to a comparison group (controls) and a group with idiopathic autism. Method The study included 53 boys between 18–42 months of age with FXS, 68 boys with idiopathic autism (ASD), and a comparison group of 50 typically-developing and developmentally-delayed controls. We examined structural brain volumes using magnetic resonance imaging (MRI) across two timepoints between ages 2–3 and 4–5 years and examined total brain volumes and regional (lobar) tissue volumes. Additionally, we studied a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala). Results Children with FXS had greater global brain volumes compared to controls, but were not different than children with idiopathic autism, and the rate of brain growth between ages 2 and 5 paralleled that seen in controls. In contrast to the children with idiopathic autism who had generalized cortical lobe enlargement, the children with FXS showed a specific enlargement in temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but significantly smaller amygdala. Conclusions This structural longitudinal MRI study of preschoolers with FXS observed generalized brain overgrowth in FXS compared to controls, evident at age 2 and maintained across ages 4–5. We also find different patterns of brain growth that distinguishes boys with FXS from children with idiopathic autism. PMID:22917205

  15. Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

    PubMed Central

    Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

    2013-01-01

    Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

  16. Is Dyslexia a Brain Disorder?

    PubMed Central

    Parrila, Rauno

    2018-01-01

    Specific word reading difficulty, commonly termed ‘developmental dyslexia’, refers to the low end of the word reading skill distribution but is frequently considered to be a neurodevelopmental disorder. This term implies that brain development is thought to be disrupted, resulting in an abnormal and dysfunctional brain. We take issue with this view, pointing out that there is no evidence of any obvious neurological abnormality in the vast majority of cases of word reading difficulty cases. The available relevant evidence from neuroimaging studies consists almost entirely of correlational and group-differences studies. However, differences in brains are certain to exist whenever differences in behavior exist, including differences in ability and performance. Therefore, findings of brain differences do not constitute evidence for abnormality; rather, they simply document the neural substrate of the behavioral differences. We suggest that dyslexia is best viewed as one of many expressions of ordinary ubiquitous individual differences in normal developmental outcomes. Thus, terms such as “dysfunctional” or “abnormal” are not justified when referring to the brains of persons with dyslexia. PMID:29621138

  17. Early Brain Vulnerability in Wolfram Syndrome

    PubMed Central

    Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan

    2012-01-01

    Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385

  18. Eye Movement Abnormalities in Joubert Syndrome

    PubMed Central

    Weiss, Avery H.; Doherty, Dan; Parisi, Melissa; Shaw, Dennis; Glass, Ian; Phillips, James O.

    2011-01-01

    Purpose Joubert syndrome is a genetic disorder characterized by hypoplasia of the midline cerebellum and deficiency of crossed connections between neural structures in the brain stem that control eye movements. The goal of the study was to quantify the eye movement abnormalities that occur in Joubert syndrome. Methods Eye movements were recorded in response to stationary stimuli and stimuli designed to elicit smooth pursuit, saccades, optokinetic nystagmus (OKN), vestibulo-ocular reflex (VOR), and vergence using video-oculography or Skalar search coils in 8 patients with Joubert syndrome. All patients underwent high-resolution magnetic resonance imaging (MRI). Results All patients had the highly characteristic molar tooth sign on brain MRI. Six patients had conjugate pendular (n = 4) or see-saw nystagmus (n = 2); gaze holding was stable in four patients. Smooth-pursuit gains were 0.28 to 1.19, 0.11 to 0.68, and 0.33 to 0.73 at peak stimulus velocities of 10, 20, and 30 deg/s in six patients; smooth pursuit could not be elicited in four patients. Saccade gains in five patients ranged from 0.35 to 0.91 and velocities ranged from 60.9 to 259.5 deg/s. Targeted saccades could not be elicited in five patients. Horizontal OKN gain was uniformly reduced across gratings drifted at velocities of 15, 30, and 45 deg/s. VOR gain was 0.8 or higher and phase appropriate in three of seven subjects; VOR gain was 0.3 or less and phase was indeterminate in four subjects. Conclusions The abnormalities in gaze-holding and eye movements are consistent with the distributed abnormalities of midline cerebellum and brain stem regions associated with Joubert syndrome. PMID:19443711

  19. Brain volumetric abnormalities in patients with anorexia and bulimia nervosa: a voxel-based morphometry study.

    PubMed

    Amianto, Federico; Caroppo, Paola; D'Agata, Federico; Spalatro, Angela; Lavagnino, Luca; Caglio, Marcella; Righi, Dorico; Bergui, Mauro; Abbate-Daga, Giovanni; Rigardetto, Roberto; Mortara, Paolo; Fassino, Secondo

    2013-09-30

    Recent studies focussing on neuroimaging features of eating disorders have observed that anorexia nervosa (AN) is characterized by significant grey matter (GM) atrophy in many brain regions, especially in the cerebellum and anterior cingulate cortex. To date, no studies have found GM atrophy in bulimia nervosa (BN) or have directly compared patients with AN and BN. We used voxel-based morphometry (VBM) to characterize brain abnormalities in AN and BN patients, comparing them with each other and with a control group, and correlating brain volume with clinical features. We recruited 17 AN, 13 BN and 14 healthy controls. All subjects underwent high-resolution magnetic resonance imaging (MRI) with a T1-weighted 3D image. VBM analysis was carried out with the FSL-VBM 4.1 tool. We found no global atrophy, but regional GM reduction in AN with respect to controls and BN in the cerebellum, fusiform area, supplementary motor area, and occipital cortex, and in the caudate in BN compared to AN and controls. Both groups of patients had a volumetric increase bilaterally in somatosensory regions with respect to controls, in areas that are typically involved in the sensory-motor integration of body stimuli and in mental representation of the body image. Our VBM study documented, for the first time in BN patients, the presence of volumetric alterations and replicated previous findings in AN patients. We evidenced morphological differences between AN and BN, demonstrating in the latter atrophy of the caudate nucleus, a region involved in reward mechanisms and processes of self-regulation, perhaps involved in the genesis of the binge-eating behaviors of this disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Abnormal Error Monitoring in Math-Anxious Individuals: Evidence from Error-Related Brain Potentials

    PubMed Central

    Suárez-Pellicioni, Macarena; Núñez-Peña, María Isabel; Colomé, Àngels

    2013-01-01

    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. PMID:24236212

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

    PubMed Central

    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

    opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = −0.27 to −0.51; P < 1.49 × 10−4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < −0.0018; P < 1.49 × 10−4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of 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

  2. Superbranes, D = 11 CJS Supergravity and Enlarged Superspace Coordinates/Fields Correspondence

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

    Azcarraga, J.A. de; IFIC - CSIC-UVEG, Facultad de Fisica, 46100-Burjassot, Valencia

    2005-04-25

    We discuss the role of enlarged superspaces in two seemingly different contexts, the structure of the p-brane actions and that of the Cremmer-Julia-Scherk eleven-dimensional supergravity. Both provide examples of a common principle: the existence of an enlarged superspaces coordinates/fields correspondence by which all the (worldvolume or spacetime) fields of the theory are associated to coordinates of enlarged superspaces. In the context of p-branes, enlarged superspaces may be used to construct manifestly supersymmetry-invariant Wess-Zumino terms and as a way of expressing the Born-Infeld worldvolume fields of D-branes and the worldvolume M5-brane two-form in terms of fields associated to the coordinates ofmore » these enlarged superspaces. This is tantamount to saying that the Born-Infeld fields have a superspace origin, as do the other worldvolume fields, and that they have a composite structure. In D=11 supergravity theory enlarged superspaces arise when its underlying gauge structure is investigated and, as a result, the composite nature of the A3 field is revealed: there is a full one-parametric family of enlarged superspace groups that solve the problem of expressing A3 in terms of spacetime fields associated to their coordinates. The corresponding enlarged supersymmetry algebras turn out to be deformations of an expansion of the osp(1 vertical bar 32) algebra. The unifying mathematical structure underlying all these facts is the cohomology of the supersymmetry algebras involved.« less

  3. European Security and NATO Enlargement: A View from Central Europe.

    DTIC Science & Technology

    1998-04-01

    8217iii 3. REPORT TYPE AND DATES COVERED Final fieport European Security and NATO Enlargement: A View from Central Europe (U) 6. AUTHOR(S) Stephen J...of views , including some not often heard, on the issues connected with NATO enlargement. 14. SUBJECT TERMS United States; NATO; post-Cold War...298-102 EUROPEAN SECURITY AND NATO ENLARGEMENT: A VIEW FROM CENTRAL EUROPE Edited by Stephen J. Blank April 1998 f"W DISTRIBUTION STATEMENT

  4. Control of Abnormal Synchronization in Neurological Disorders

    PubMed Central

    Popovych, Oleksandr V.; Tass, Peter A.

    2014-01-01

    In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

  5. A three-dimensional definition of nodal spaces on the basis of CT images showing enlarged nodes for pelvic radiotherapy

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

    Portaluri, Maurizio; Bambace, Santa; Perez, Celeste

    2005-11-15

    Purpose: To demonstrate that margins of each pelvic chain may be derived by verifying the bony and soft tissue structures around abnormal nodes on computed tomography (CT) slices. Methods and Materials: Twenty consecutive patients (16 males, 4 females; mean age, 66 years; range, 43-80 years) with radiologic diagnosis of nodal involvement by histologically proved cervix carcinoma (two), rectum carcinoma (three), prostate carcinoma (four), lymphoma (five), penis carcinoma (one), corpus uteri carcinoma (one), bladder carcinoma (two), cutis tumor (one), and soft-tissue sarcoma (one) were retrospectively reviewed. One hundred CT scans showing 85 enlarged pelvic nodes were reviewed by two radiation oncologistsmore » (M.P., S.B.), and two radiologists (C.P., G.A.). Results: The more proximal structures to each enlarged node or group of nodes were thus recorded in a clockwise direction. Conclusion: According to their frequency and visibility, craniocaudal, anterior, lateral, posterior and medial margins of common iliac, external and internal iliac nodal chains, obturator and pudendal nodes, and deep and superficial inguinal nodes were derived from CT observations.« less

  6. Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

    PubMed

    Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

    2017-05-01

    Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

  7. Embracing covariation in brain evolution: Large brains, extended development, and flexible primate social systems

    PubMed Central

    Charvet, Christine J.; Finlay, Barbara L.

    2012-01-01

    Brain size, body size, developmental length, life span, costs of raising offspring, behavioral complexity, and social structures are correlated in mammals due to intrinsic life-history requirements. Dissecting variation and direction of causation in this web of relationships often draw attention away from the factors that correlate with basic life parameters. We consider the “social brain hypothesis,” which postulates that overall brain and the isocortex are selectively enlarged to confer social abilities in primates, as an example of this enterprise and pitfalls. We consider patterns of brain scaling, modularity, flexibility of brain organization, the “leverage,” and direction of selection on proposed dimensions. We conclude that the evidence supporting selective changes in isocortex or brain size for the isolated ability to manage social relationships is poor. Strong covariation in size and developmental duration coupled with flexible brains allow organisms to adapt in variable social and ecological environments across the life span and in evolution. PMID:22230623

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

    PubMed

    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.

  9. Brain abnormalities in antisocial individuals: implications for the law.

    PubMed

    Yang, Yaling; Glenn, Andrea L; Raine, Adrian

    2008-01-01

    With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

  10. Abnormal Structure–Function Relationship in Spasmodic Dysphonia

    PubMed Central

    Ludlow, Christy L.

    2012-01-01

    Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

  11. Phospholipids Trigger Cryptococcus neoformans Capsular Enlargement during Interactions with Amoebae and Macrophages

    PubMed Central

    Chrisman, Cara J.; Albuquerque, Patricia; Guimaraes, Allan J.; Nieves, Edward; Casadevall, Arturo

    2011-01-01

    A remarkable aspect of the interaction of Cryptococcus neoformans with mammalian hosts is a consistent increase in capsule volume. Given that many aspects of the interaction of C. neoformans with macrophages are also observed with amoebae, we hypothesized that the capsule enlargement phenomenon also had a protozoan parallel. Incubation of C. neoformans with Acanthamoeba castellanii resulted in C. neoformans capsular enlargement. The phenomenon required contact between fungal and protozoan cells but did not require amoeba viability. Analysis of amoebae extracts showed that the likely stimuli for capsule enlargement were protozoan polar lipids. Extracts from macrophages and mammalian serum also triggered cryptococcal capsular enlargement. C. neoformans capsule enlargement required expression of fungal phospholipase B, but not phospholipase C. Purified phospholipids, in particular, phosphatidylcholine, and derived molecules triggered capsular enlargement with the subsequent formation of giant cells. These results implicate phospholipids as a trigger for both C. neoformans capsule enlargement in vivo and exopolysaccharide production. The observation that the incubation of C. neoformans with phospholipids led to the formation of giant cells provides the means to generate these enigmatic cells in vitro. Protozoan- or mammalian-derived polar lipids could represent a danger signal for C. neoformans that triggers capsular enlargement as a non-specific defense mechanism against potential predatory cells. Hence, phospholipids are the first host-derived molecules identified to trigger capsular enlargement. The parallels apparent in the capsular response of C. neoformans to both amoebae and macrophages provide additional support for the notion that certain aspects of cryptococcal virulence emerged as a consequence of environmental interactions with other microorganisms such as protists. PMID:21637814

  12. 3D PATTERN OF BRAIN ABNORMALITIES IN FRAGILE X SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    PubMed Central

    Lee, Agatha D.; Leow, Alex D.; Lu, Allen; Reiss, Allan L.; Hall, Scott; Chiang, Ming-Chang; Toga, Arthur W.; Thompson, Paul M.

    2007-01-01

    Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/−1.58SD, 18 females/18 males), and 33 age-matched healthy controls (age: 14.67+/−2.2SD, 17 females/16 males), using high-dimensional elastic image registration. All 69 subjects' 3D T1-weighted brain MRIs were spatially deformed to match a high-resolution single-subject average MRI scan in ICBM space, whose geometry was optimized to produce a minimal deformation target. Maps of the local Jacobian determinant (expansion factor) were computed from the deformation fields. Statistical maps showed increased caudate (10% higher; p=0.001) and lateral ventricle volumes (19% higher; p=0.003), and trend-level parietal and temporal white matter excesses (10% higher locally; p=0.04). In affected females, volume abnormalities correlated with reduction in systemically measured levels of the fragile X mental retardation protein (FMRP; Spearman's r<−0.5 locally). Decreased FMRP correlated with ventricular expansion (p=0.042; permutation test), and anterior cingulate tissue reductions (p=0.0026; permutation test) supporting theories that FMRP is required for normal dendritic pruning in fronto-striatal-limbic pathways. No sex differences were found; findings were confirmed using traditional volumetric measures in regions of interest. Deficit patterns were replicated using Lie group statistics optimized for tensor-valued data. Investigation of how these anomalies emerge over time will accelerate our understanding of FraX and its treatment. PMID:17161622

  13. Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

    PubMed Central

    Martínez-Montes, Eduardo

    2013-01-01

    This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

  14. Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

    PubMed Central

    Roussotte, Florence; Soderberg, Lindsay

    2010-01-01

    Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

  15. Abnormal parietal encephalomalacia associated with schizophrenia: A case report.

    PubMed

    Pan, Fen; Wang, Jun-Yuan; Xu, Yi; Huang, Man-Li

    2017-03-01

    It is widely believed that structural abnormalities of the brain contribute to the pathophysiology of schizophrenia. The parietal lobe is a central hub of multisensory integration, and abnormities in this region might account for the clinical features of schizophrenia. However, few cases of parietal encephalomalacia associated with schizophrenia have been described. In this paper, we present a case of a 25-year-old schizophrenia patient with abnormal parietal encephalomalacia. The patient had poor nutrition and frequently had upper respiratory infections during childhood and adolescence. She showed severe schizophrenic symptoms such as visual hallucinations for 2 years. After examining all her possible medical conditions, we found that the patient had a lesion consistent with the diagnosis of encephalomalacia in her right parietal lobe and slight brain atrophy. The patient was prescribed olanzapine (10 mg per day). Her symptoms significantly improved after antipsychotic treatment and were still well controlled 1 year later. This case suggested that parietal encephalomalacia, which might be caused by inflammatory and infectious conditions in early life and be aggravated by undernutrition, might be implicated in the etiology of schizophrenia.

  16. Abnormal Reward System Activation in Mania

    PubMed Central

    Abler, Birgit; Greenhouse, Ian; Ongur, Dost; Walter, Henrik; Heckers, Stephan

    2008-01-01

    Transmission of reward signals is a function of dopamine, a neurotransmitter known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), we investigated how expectation and receipt of monetary rewards modulate brain activation in patients with bipolar mania and schizophrenia. We studied 12 acutely manic patients with a history of bipolar disorder, 12 patients with a current episode of schizoaffective disorder or schizophrenia and 12 healthy subjects. All patients were treated with dopamine antagonists at the time of the study. Subjects performed a delayed incentive paradigm with monetary reward in the scanner that allowed for investigating effects of expectation, receipt, and omission of rewards. Patients with schizophrenia and healthy control subjects showed the expected activation of dopaminergic brain areas, that is, ventral tegmentum activation upon expectation of monetary rewards and nucleus accumbens activation during receipt vs omission of rewards. In manic patients, however, we did not find a similar pattern of brain activation and the differential signal in the nucleus accumbens upon receipt vs omission of rewards was significantly lower compared to the healthy control subjects. Our findings provide evidence for abnormal function of the dopamine system during receipt or omission of expected rewards in bipolar disorder. These deficits in prediction error processing in acute mania may help to explain symptoms of disinhibition and abnormal goal pursuit regulation. PMID:17987058

  17. Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

    PubMed Central

    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. PMID:27891090

  18. [Forensic application of brainstem auditory evoked potential in patients with brain concussion].

    PubMed

    Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin

    2008-12-01

    To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (P<0.05). The abnormal rate of BAEP in the brainstem pathway for patients with brain concussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

  19. Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain Injury Are Partially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189

    PubMed Central

    McAfee, Samuel S.; Guley, Natalie M.; Del Mar, Nobel; Bu, Wei; Heldt, Scott A.; Honig, Marcia G.; Moore, Bob M.

    2017-01-01

    Abstract 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. PMID:28828401

  20. Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain Injury Are Partially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189.

    PubMed

    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.

  1. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study.

    PubMed

    Inder, Terrie E; Wells, Scott J; Mogridge, Nina B; Spencer, Carole; Volpe, Joseph J

    2003-08-01

    The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Women's Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse

  2. Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.

    PubMed

    Gripp, Karen W; Zand, Dina J; Demmer, Laurie; Anderson, Carol E; Dobyns, William B; Zackai, Elaine H; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L; Sol-Church, Katia

    2013-10-01

    Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities, and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay, and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4; 75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. Copyright © 2013 Wiley Periodicals, Inc.

  3. Utility of brain MRI in children with sleep-disordered breathing.

    PubMed

    Selvadurai, Sarah; Al-Saleh, Suhail; Amin, Reshma; Zweerink, Allison; Drake, James; Propst, Evan J; Narang, Indra

    2017-02-01

    To investigate the utility of a brain magnetic resonance imaging (MRI) in children with sleep-disordered breathing (SDB), classified as isolated obstructive sleep apnea (OSA) in the absence of adenotonsillar hypertrophy, persistent OSA following adenotonsillectomy, isolated central sleep apnea (CSA) of unclear etiology, OSA with coexisting CSA of unclear etiology, or unexplained nocturnal hypoventilation (NH). Retrospective chart review of polysomnography (PSG) and brain MRI data. Children with PSG evidence of SDB, as described above, and who subsequently had their first brain MRI, were included. PSG, MRI data, and subsequent interventions were recorded. A total of 59 of 6,087 (1%) children met inclusion criteria. Of those, 28 of 59 (47%) were nonsyndromic children and 31 of 59 (53%) were syndromic children with an underlying medical disorder. Abnormal brain MRI findings were observed in 19 of 59 (32%) children, where eight of 19 (42%) were nonsyndromic and 11 of 19 (58%) were syndromic. Abnormal brain MRI findings were most common in syndromic children with combined OSA and CSA without adenotonsillar hypertrophy. Isolated OSA was also a common PSG finding associated with an abnormal brain MRI. Of the nonsyndromic children with an abnormal brain MRI, the most common abnormal brain MRI finding was Chiari malformation (CM), observed in 88% of the group. A brainstem tumor was identified in one nonsyndromic child. Interventions following brain MRI included neurosurgery, chemotherapy, and noninvasive positive pressure ventilation (NiPPV). A brain MRI is an important diagnostic tool in syndromic and nonsyndromic children, especially in children with either isolated OSA or combined OSA and CSA without a clear etiology. 4. Laryngoscope, 2016 127:513-519, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  4. [Transient enlargement of craniopharyngioma cysts after stereotactic radiotherapy and radiosurgery].

    PubMed

    Mazerkina, N A; Savateev, A N; Gorelyshev, S K; Konovalov, A N; Trunin, Yu Yu; Golanov, A V; Medvedeva, O A; Kalinin, P L; Kutin, M A; Astafieva, L I; Krasnova, T S; Ozerova, V I; Serova, N K; Butenko, E I; Strunina, Yu V

    Stereotactic radiotherapy/radiosurgery (RT/ES) is an effective technique for treating craniopharyngiomas (CPs). However, enlargement of the cystic part of the tumor occurs in some cases after irradiation. The enlargement may be transient and not require treatment or be a true relapse requiring treatment. In this study, we performed a retrospective analysis of 79 pediatric patients who underwent stereotactic RT or RS after resection of craniopharyngioma. Five-year relapse-free survival after complex treatment of CP was 86%. In the early period after irradiation, 3.5 months (2.7-9.4) on average, enlargement of the cystic component of the tumor was detected in 10 (12.7%) patients; in 9 (11.4%) of them, the enlargement was transient and did not require treatment; in one case, the patient underwent surgery due to reduced visual acuity. In 8 (10.1%) patients, an increase in the residual tumor (a solid component of the tumor in 2 cases and a cystic component of the tumor in 6 cases) occurred in the long-term period after irradiation - after 26.3 months (16.6-48.9) and did not decrease during follow-up in none of the cases, i.e. continued growth of the tumor was diagnosed. A statistical analysis revealed that differences in the terms of transient enlargement and true continued growth were statistically significant (p<0.01). Enlargement of a craniopharyngioma cyst in the early period (up to 1 year) after RT/RS is usually transient and does not require surgical treatment (except cases where worsening of neurological symptoms occurs, or occlusive hydrocephalus develops).

  5. Genetics Home Reference: enlarged parietal foramina

    MedlinePlus

    ... parietal foramina is an inherited condition of impaired skull development. It is characterized by enlarged openings (foramina) ... that form the top and sides of the skull. This condition is due to incomplete bone formation ( ...

  6. Successfully use agglomeration for size enlargement

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

    Pietsch, W.

    1996-04-01

    The processing of fine and ultrafine particles by size enlargement finds an ever increasing application. At the same time, undesirable agglomeration such as buildup, caking, bridging, and uncontrolled aggregation of fine particles can occur during processing and handling of these particulate solids. This article will provide a survey of the phenomena of agglomeration and discuss the unit operation of size enlargement by agglomeration. This article is also an invitation, particularly to young engineers, to become interested in agglomeration. Considering that mechanical process technologies are requiring more energy every year than any other group of consumers and efficiencies are typically inmore » the single digits or teens at best, considerable rewards can be expected from the development of scientifically modified, more energy-efficient methods and equipment.« less

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

    PubMed Central

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

    2005-01-01

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

  8. Axonal abnormalities in vanishing white matter.

    PubMed

    Klok, Melanie D; Bugiani, Marianna; de Vries, Sharon I; Gerritsen, Wouter; Breur, Marjolein; van der Sluis, Sophie; Heine, Vivi M; Kole, Maarten H P; Baron, Wia; van der Knaap, Marjo S

    2018-04-01

    We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, astrocyte-forebrain co-culture studies were performed. In the corpus callosum of Eif2b5- mutant mice, myelin sheath thickness, axonal diameter, and G-ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G-ratio in Eif2b5- mutant mice. In more severely affected Eif2b4-Eif2b5 double-mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5 -mutant mice. Co-cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal. In vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.

  9. [Ocular coloboma and results of brain MRI: preliminary results].

    PubMed

    Denis, D; Girard, N; Levy-Mozziconacci, A; Berbis, J; Matonti, F

    2013-03-01

    Congenital ocular colobomas are the result of a failure in closure of the embryonal fissure. We present a prospective study (2007-2011) in which we report brain MRI findings in children with ocular coloboma. Thirty-five children (54 eyes) were included; 15 boys, 20 girls with a median age of 24.0 months (1.0-96.0) at first presentation. Within 2 to 3 months following complete ophthalmologic examination, brain MRI was performed. Colobomas were bilateral in 19 cases and unilateral in 16 cases. Eleven different types of coloboma were identified. Of 54 eyes, 74% demonstrated optic nerve coloboma, of which 28 were severe. Of 35 MRI's performed, abnormalities were present in 86%: gyration abnormalities (n=21), lateral ventricular dilatation (n=17), dilatation of the Virchow-Robin and subarachnoid spaces (n=14), signal abnormalities and brain stem malformations (n=14), white matter signal abnormalities (n=11), corpus callosum abnormalities (n=10). Most of these abnormalities were related. Gyration abnormalities were the most frequent. There was no significant association between the severity of the coloboma and the abnormalities found (P=1.0). Likewise, there was no significant association of gyration abnormalities with the severity of coloboma in children (P=1.0). This study shows, for the first time, the existence of frequent cerebral abnormalities on MRI in children with ocular coloboma. The most common abnormality being gyration abnormalities, in 60% of cases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

    PubMed Central

    Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

    2015-01-01

    Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

  11. Characteristics of vestibular evoked myogenic potentials in children with enlarged vestibular aqueduct.

    PubMed

    Zhou, Guangwei; Gopen, Quinton

    2011-01-01

    To explore the characteristics of vestibular evoked myogenic potential (VEMP) in children with enlarged vestibular aqueduct (EVA) and to determine the diagnostic value of VEMP testing for this particular inner ear structural anomaly. Retrospective cohort study in a pediatric tertiary care facility. A total of 25 pediatric cases (37 ears) of EVA were identified with complete records, including otologic evaluation, CT scan of the temporal bone, and audiologic assessment. Results of audiometry, tympanometry, and VEMP testing were analyzed. Hearing loss was found in 97% (36/37) of the ears with EVA. Airbone gaps (conductive components) were found in all hearing losses with normal middle ear pressure and mobility. Abnormally low threshold VEMP responses were found in 92% (34/37) of the ears with EVA. VEMP responses were absent unilaterally in three EVA patients who had vestibular complaints. No clear correlation was found between the size of EVA and the audiologic findings. The presence of airbone gaps in children with EVA was found without apparent middle ear pathology. Characteristics of VEMP in EVA were lower thresholds and higher amplitudes despite of the presence of airbone gaps. The abnormally low threshold VEMP responses suggested a "third" window effect in the pathologic condition of EVA. Unilateral absence of VEMP may implicate peripheral vestibular impairment. The findings from our study are helpful in clinical evaluation of young children who usually give limited and ambiguous input regarding their hearing and vestibular problems.

  12. Chromosomal aneuploidies and copy number variations in posterior fossa abnormalities diagnosed by prenatal ultrasonography.

    PubMed

    Lei, Ting; Feng, Jie-Ling; Xie, Ying-Jun; Xie, Hong-Ning; Zheng, Ju; Lin, Mei-Fang

    2017-11-01

    To explore the genetic aetiology of fetal posterior fossa abnormalities (PFAs). This study involved cases of PFAs that were identified by prenatal ultrasonographic screening and confirmed postnatally between January 2012 and January 2016. Conventional cytogenetic analyses and chromosomal microarray analysis were performed, and chromosomal aneuploidies and copy number variations (CNVs) were identified. Among 74 cases included in this study, 8 were of Blake's pouch cyst; 7, Dandy-Walker malformation; 11, vermian hypoplasia; 32, enlarged cisterna magna; and 16, cerebellar hypoplasia. The rates of nonbenign chromosomal aberrations (including chromosomal aneuploidies, pathogenic CNVs, and variants of unknown significance) were 2/8 (25.0%), 2/7 (28.5%), 8/11 (72.7%), 7/32 (21.9%), and 6/16 (37.5%), respectively. Cases were also classified as isolated PFAs (30/74), PFAs with other central nervous system (CNS) abnormalities (13/74), or PFAs with extra-CNS structural abnormalities (31/74). No fetuses with isolated PFAs or PFAs accompanied by other CNS abnormalities exhibited chromosomal aneuploidies or pathogenic CNVs. The rate of pathogenic chromosomal aberrations in the remaining fetuses was 17/31 (22.9%). The combined use of chromosomal microarray analysis and karyotype analysis might assist the prenatal diagnosis and management of PFAs, with extra-CNS structural abnormalities being detected by ultrasonography. © 2017 John Wiley & Sons, Ltd.

  13. Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination.

    PubMed

    Pugash, D; Hendson, G; Dunham, C P; Dewar, K; Money, D M; Prayer, D

    2012-12-01

    Prenatal development of the brain is characterized by gestational age-specific changes in the laminar structure of the brain parenchyma before 30 gestational weeks. Cerebral lamination patterns of normal fetal brain development have been described histologically, by postmortem in-vitro magnetic resonance imaging (MRI) and by in-vivo fetal MRI. The purpose of this study was to evaluate the sonographic appearance of laminar organization of the cerebral wall in normal and abnormal brain development. This was a retrospective study of ultrasound findings in 92 normal fetuses and 68 fetuses with abnormal cerebral lamination patterns for gestational age, at 17-38 weeks' gestation. We investigated the visibility of the subplate zone relative to the intermediate zone and correlated characteristic sonographic findings of cerebral lamination with gestational age in order to evaluate transient structures. In the normal cohort, the subplate zone-intermediate zone interface was identified as early as 17 weeks, and in all 57 fetuses examined up to 28 weeks. In all of these fetuses, the subplate zone appeared anechoic and the intermediate zone appeared homogeneously more echogenic than did the subplate zone. In the 22 fetuses between 28 and 34 weeks, there was a transition period when lamination disappeared in a variable fashion. The subplate zone-intermediate zone interface was not identified in any fetus after 34 weeks (n=13). There were three patterns of abnormal cerebral lamination: (1) no normal laminar pattern before 28 weeks (n=32), in association with severe ventriculomegaly, diffuse ischemia, microcephaly, teratogen exposure or lissencephaly; (2) focal disruption of lamination before 28 weeks (n=24), associated with hemorrhage, porencephaly, stroke, migrational abnormalities, thanatophoric dysplasia, meningomyelocele or encephalocele; (3) increased prominence and echogenicity of the intermediate zone before 28 weeks and/or persistence of a laminar pattern beyond 33 weeks

  14. Neural correlates of abnormal sensory discrimination in laryngeal dystonia.

    PubMed

    Termsarasab, Pichet; Ramdhani, Ritesh A; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J; Reilly, Richard B; Hutchinson, Michael; Ozelius, Laurie J; Simonyan, Kristina

    2016-01-01

    Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

  15. [INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

    PubMed

    Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

    2016-03-30

    Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

  16. Fetal Alcohol Spectrum Disorders and Abnormal Neuronal Plasticity

    PubMed Central

    Medina, Alexandre E.

    2012-01-01

    The ingestion of alcohol during pregnancy can result in a group of neurobehavioral abnormalities collectively known as fetal alcohol spectrum disorders (FASD). During the past decade, studies using animal models indicated that early alcohol exposure can dramatically affect neuronal plasticity, an essential property of the central nervous system responsible for the normal wiring of the brain and involved in processes such as learning and memory. The abnormalities in neuronal plasticity caused by alcohol can explain many of the neurobehavioral deficits observed in FASD. Conversely, improving neuronal plasticity may have important therapeutic benefits. In this review, the author discuss the mechanisms that lead to these abnormalities and comment on recent pharmacological approaches that have been showing promising results in improving neuronal plasticity in FASD. PMID:21383101

  17. Brain anomalies in velo-cardio-facial syndrome

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

    Mitnick, R.J.; Bello, J.A.; Shprintzen, R.J.

    Magnetic resonance imaging of the brain in 11 consecutively referred patients with velo-cardio-facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal horns, and small posterior fossa. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild development delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavorial findings showed no specific pattern related to the brain anomalies, and the patients withmore » VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. 25 refs.« less

  18. Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.

    PubMed

    Lim, L; Hart, H; Mehta, M; Worker, A; Simmons, A; Mirza, K; Rubia, K

    2018-04-01

    Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.

  19. SPECT brain perfusion findings in mild or moderate traumatic brain injury.

    PubMed

    Abu-Judeh, H H; Parker, R; Aleksic, S; Singh, M L; Naddaf, S; Atay, S; Kumar, M; Omar, W; El-Zeftawy, H; Luo, J Q; Abdel-Dayem, H M

    2000-01-01

    The purpose of this manuscript is to present the findings in the largest series of SPECT brain perfusion imaging reported to date for mild or moderate traumatic brain injury. This is a retrospective evaluation of 228 SPECT brain perfusion-imaging studies of patients who suffered mild or moderate traumatic brain injury with or without loss of consciousness (LOC). All patients had no past medical history of previous brain trauma, neurological, or psychiatric diseases, HIV, alcohol or drug abuse. The patient population included 135 males and 93 females. The ages ranged from 11-88 years (mean 40.8). The most common complaints were characteristic of the postconcussion syndrome: headaches 139/228 (61%); dizziness 61/228 (27%); and memory problems 63/228 (28%). LOC status was reported to be positive in 121/228 (53%), negative in 41/228 (18%), and unknown for 63/228 (28%). Normal studies accounted for 52/228 (23%). For abnormal studies (176/228 or 77%) the findings were as follows: basal ganglia hypoperfusion 338 lesions (55.2%); frontal lobe hypoperfusion 146 (23.8%); temporal lobes hypoperfusion 80 (13%); parietal lobes hypoperfusion 20 (3.7%); insular and or occipital lobes hypoperfusion 28 (4.6%). Patients' symptoms correlated with the SPECT brain perfusion findings. The SPECT BPI studies in 122/228 (54%) were done early within 3 months of the date of the accident, and for the remainder, 106/228 (46%) over 3 months and less than 3 years from the date of the injury. In early imaging, 382 lesions were detected; in 92 patients (average 4.2 lesions per study) imaging after 3 months detected 230 lesions: in 84 patients (average 2.7 lesions per study). Basal ganglia hypoperfusion is the most common abnormality following mild or moderate traumatic brain injury (p = 0.006), and is more common in patients complaining of memory problem (p = 0.0005) and dizziness (p = 0.003). Early imaging can detect more lesions than delayed imaging (p = 0.0011). SPECT brain perfusion

  20. Association of a Guardian’s Report of a Child Acting Abnormally With Traumatic Brain Injury After Minor Blunt Head Trauma

    PubMed Central

    Nishijima, Daniel K.; Holmes, James F.; Dayan, Peter S.; Kuppermann, Nathan

    2016-01-01

    IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. EXPOSURES A guardian report that the child was acting abnormally after minor blunt head trauma. MAIN OUTCOMES AND MEASURES 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. RESULTS 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. CONCLUSIONS AND RELEVANCE Clinically important TBIs are very uncommon, and TBIs

  1. Continuum of neurobehaviour and its associations with brain MRI in infants born preterm

    PubMed Central

    Eeles, Abbey L; Walsh, Jennifer M; Olsen, Joy E; Cuzzilla, Rocco; Thompson, Deanne K; Anderson, Peter J; Doyle, Lex W; Cheong, Jeanie L Y; Spittle, Alicia J

    2017-01-01

    Background Infants born very preterm (VPT) and moderate-to-late preterm (MLPT) are at increased risk of long-term neurodevelopmental deficits, but how these deficits relate to early neurobehaviour in MLPT children is unclear. The aims of this study were to compare the neurobehavioural performance of infants born across three different gestational age groups: preterm <30 weeks’ gestational age (PT<30); MLPT (32–36 weeks’ gestational age) and term age (≥37 weeks’ gestational age), and explore the relationships between MRI brain abnormalities and neurobehaviour at term-equivalent age. Methods Neurobehaviour was assessed at term-equivalent age in 149 PT<30, 200 MLPT and 200 term-born infants using the Neonatal Intensive Care UnitNetwork Neurobehavioral Scale (NNNS), the Hammersmith Neonatal Neurological Examination (HNNE) and Prechtl’s Qualitative Assessment of General Movements (GMA). A subset of 110 PT<30 and 198 MLPT infants had concurrent brain MRI. Results Proportions with abnormal neurobehaviour on the NNNS and the HNNE, and abnormal GMA all increased with decreasing gestational age. Higher brain MRI abnormality scores in some regions were associated with suboptimal neurobehaviour on the NNNS and HNNE. The relationships between brain MRI abnormality scores and suboptimal neurobehaviour were similar in both PT<30 and MLPT infants. The relationship between brain MRI abnormality scores and abnormal GMA was stronger in PT<30 infants. Conclusions There was a continuum of neurobehaviour across gestational ages. The relationships between brain abnormality scores and suboptimal neurobehaviour provide evidence that neurobehavioural assessments offer insight into the integrity of the developing brain, and may be useful in earlier identification of the highest-risk infants. PMID:29637152

  2. Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I.

    PubMed

    Harting, Inga; Neumaier-Probst, Eva; Seitz, Angelika; Maier, Esther M; Assmann, Birgit; Baric, Ivo; Troncoso, Monica; Mühlhausen, Chris; Zschocke, Johannes; Boy, Nikolas P S; Hoffmann, Georg F; Garbade, Sven F; Kölker, Stefan

    2009-07-01

    In glutaric aciduria type I, an autosomal recessive disease of mitochondrial lysine, hydroxylysine and tryptophan catabolism, striatal lesions are characteristically induced by acute encephalopathic crises during a finite period of brain development (age 3-36 months). The frequency of striatal injury is significantly less in patients diagnosed as asymptomatic newborns by newborn screening. Most previous studies have focused on the onset and mechanism of striatal injury, whereas little is known about neuroradiological abnormalities in pre-symptomatically diagnosed patients and about dynamic changes of extrastriatal abnormalities. Thus, the major aim of the present retrospective study was to improve our understanding of striatal and extrastriatal abnormalities in affected individuals including those diagnosed by newborn screening. To this end, we systematically analysed magnetic resonance imagings (MRIs) in 38 patients with glutaric aciduria type I diagnosed before or after the manifestation of neurological symptoms. To identify brain regions that are susceptible to cerebral injury during acute encephalopathic crises, we compared the frequency of magnetic resonance abnormalities in patients with and without such crises. Major specific changes after encephalopathic crises were found in the putamen (P < 0.001), nucleus caudatus (P < 0.001), globus pallidus (P = 0.012) and ventricles (P = 0.001). Analysis of empirical cumulative distribution frequencies, however, demonstrated that isolated pallidal abnormalities did not significantly differ over time in both groups (P = 0.544) suggesting that isolated pallidal abnormalities are not induced by acute crises--in contrast to striatal abnormalities. The manifestation of motor disability was associated with signal abnormalities in putamen, caudate, pallidum and ventricles. In addition, we found a large number of extrastriatal abnormalities in patients with and without preceding encephalophatic crises. These abnormalities

  3. Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI.

    PubMed

    Franceschi, Ana M; Matthews, Robert; Bangiyev, Lev; Relan, Nand; Chaudhry, Ammar; Franceschi, Dinko

    2018-05-24

    FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients.

  4. Chronic lymphoglandular enlargement and toxoplasmosis in children.

    PubMed Central

    Thomaidis, T; Anastassea-Vlachou, K; Mandalenaki-Lambrou, C; Theodoridis, C; Vrahnou, E

    1977-01-01

    Serum antitoxoplasma titres were determined simultaneously by the direct agglutination and the indirect immunofluorescent tests in 52 children aged 2 to 16 years having chronic lymph node enlargement, mainly cervical. Direct agglutination titres were raised (64 to 4096) in 22 children (42%), but rarely in the control groups of children with acute suppurative lymphadenitis, and healthy children, adults, nurses, and physicians. It is concluded that toxoplasmosis is commoner in Greek children than previously believed, and that it should be included in the differential diagnosis of lymphoglandular enlargement. Clinically the condition is mild and may be self-limited, but it should be treated promptly with trimethoprim-sulphamethoxazole, in order to prevent reactivation in adult life. PMID:326200

  5. Glomerular enlargement assessed by paired donor and early protocol renal allograft biopsies.

    PubMed

    Alperovich, Gabriela; Maldonado, Rafael; Moreso, Francesc; Fulladosa, Xavier; Grinyó, Josep M; Serón, Daniel

    2004-04-01

    The aim of the study was to evaluate the evolution of glomerular volume 4 months after transplantation. Mean glomerular volume (Vg) was estimated according to the Weibel and Gomez method in a donor and a protocol biopsy done at 139 +/- 58 d in 41 stable grafts. Biopsies were also evaluated according to the Banff schema. Vg increased after transplantation from 4.1 +/- 1.4 to 5.1 +/- 2.4 x 10(6) micro3 (p=0.02). In patients with chronic allograft nephropathy in the protocol biopsy (n=14), the Vg enlargement was -0.3 +/-x 10(6) micro3 while in patients without chronic allograft nephropathy (n=27), glomerular enlargement was 1.6 +/- 2.1 x 10(6) micro3 (p=0.01). There was a negative association between glomerular volume in the donor biopsy and glomerular enlargement after transplantation (R=- 0.34, p=0.03). Multivariate regression analysis confirmed that Vg in the donor biopsy and chronic allograft nephropathy in the protocol biopsy were independent predictors of glomerular enlargement after transplantation (R=0.48, p=0.01). Moreover, Vg in the protocol biopsy correlated with creatinine clearance at the time of biopsy (R=0.38, p=0.01). Glomeruli enlarge after transplantation and glomerular volume after 4 months correlates with creatinine clearance, suggesting that glomerular enlargement is a necessary condition for renal adaptation to the recipient. Glomerular enlargement is impaired in patients with chronic allograft nephropathy.

  6. The role of white matter abnormalities in treatment-resistant depression: a systematic review.

    PubMed

    Serafini, Gianluca; Pompili, Maurizio; Borgwardt, Stefan; Giuffra, Enrico; Howes, Oliver; Girardi, Paolo; Amore, Mario

    2015-01-01

    Patients with treatment-resistant depression (TRD) commonly report significant disability together with an increased risk of functional impairment. Neuroimaging techniques have been used to investigate the neuropathology of this complex illness, but it is still quite unknown whether abnormalities in the integrity of white matter (WM) of specific brain areas may be considered as trait markers of TRD. Electronic databases were searched from 1980 to 2013. Nine studies - comprising a total of 228 subjects and 171 controls - fulfilled our inclusion criteria and were analyzed in the present overview. Several cross-sectional studies showed the association between WM abnormalities and TRD. According to the selected studies, sub-callosal cingulated cortex (SCC) WM abnormalities were largely implicated in the pathogenesis of both major depressive disorder and TRD. However, alterations in cortical-limbic or cortical-subcortical circuits, particularly the left middle frontal gyrus (which is thought to have a major role in emotional regulation) may also be involved in the pathophysiology of TRD. TRD may be related to the presence of specific microstructural WM abnormalities. WM abnormalities of specific brain regions such as SCC may have a major involvement in the pathogenesis of TRD.

  7. Mapping the dense scotoma and its enlargement in Stargardt disease

    PubMed Central

    Bernstein, Aryeh; Sunness, Janet S.; Applegate, Carol A.; Tegins, Elizabeth O.

    2016-01-01

    Purpose To describe the enlargement of the dense scotoma over time in Stargardt disease, and to highlight methodological issues in tracking enlargement. Methods Retrospective study of patients with full mapping of the border of the dense scotoma using the MP-1 for at least two visits. Results Fourteen eyes of 7 patients met this criterion. Patients had median of 3 visits (range 2 to 5), with median total f/u of 4.5 years (range 1.5-8). Mean baseline visual acuity was 20/56 (range 20/25-20/200), mean baseline dense scotoma area was 2.23mm2 (range 0.41-5.48), and mean dense scotoma enlargement rate was 1.36mm2/year (range 0.22-2.91). The younger patients tended to have more rapid loss of visual acuity, which tended to plateau when the VA was 20/100 or worse. The patients who developed Stargardt before age 20, and the single patient who developed Stargardt disease after age 40, had more rapid enlargement rates, with preservation of central vision in the oldest patient. The ability to precisely define the dense scotoma area was dependent upon the density location of the points tested; this led to significant variability in the assessment of the scotoma enlargement rate in 3 of the 7 patients. The dense scotoma was not described adequately by the extent of the homogeneous dark area on fundus autofluorescence imaging. Conclusion Microperimetry is necessary for mapping the scotoma in patients with Stargardt disease, since current imaging is not adequate. Standardized grid testing, plus a standardized procedure for refining the border of the dense scotoma, should allow more precise testing and longitudinal assessment of enlargement rates. PMID:26909568

  8. TSPO Expression and Brain Structure in the Psychosis Spectrum.

    PubMed

    Hafizi, Sina; Guma, Elisa; Koppel, Alex; Da Silva, Tania; Kiang, Michael; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Chakravarty, M Mallar; Mizrahi, Romina

    2018-06-12

    Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [ 18 F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [ 18 F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [ 18 F]FEPPA V T (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [ 18 F]FEPPA V T and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis. Copyright © 2018. Published by Elsevier Inc.

  9. Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

    PubMed

    Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

    2015-06-01

    The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of

  10. Calf enlargement associated with neurologic disease: two uncommon cases.

    PubMed

    Harwood, S C; Honet, J C

    1988-01-01

    Muscle enlargement and hypertrophy are rare findings in neurogenic lesions. The two in combination have been reported in cases of peripheral nerve lesions, polyneuropathy, and poliomyelitis. True and pseudo muscle hypertrophy are the two possible etiologies, whereas infiltration, stretch, or exercise of the muscle are the causative factors. We report two cases of unilateral calf enlargement, one occurring after surgery for S1 radiculopathy with associated cramping, and the other after poliomyelitis.

  11. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

    PubMed Central

    Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

    2015-01-01

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

  12. Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

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

    Wang, G.J.; Volkow, N.D.; Lau, Y.H.

    1994-05-01

    This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions ofmore » interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.« less

  13. Brain ultrasound findings in neonates treated with intrauterine transfusion for fetal anaemia.

    PubMed

    Leijser, Lara M; Vos, Nikki; Walther, Frans J; van Wezel-Meijler, Gerda

    2012-09-01

    The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce. To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome. Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability). A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome. Neonates undergoing IUT for fetal anaemia are at high risk of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Neonatal brain resting-state functional connectivity imaging modalities.

    PubMed

    Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

    2018-06-01

    Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

  15. A fossil brain from the Cretaceous of European Russia and avian sensory evolution.

    PubMed

    Kurochkin, Evgeny N; Dyke, Gareth J; Saveliev, Sergei V; Pervushov, Evgeny M; Popov, Evgeny V

    2007-06-22

    Fossils preserving traces of soft anatomy are rare in the fossil record; even rarer is evidence bearing on the size and shape of sense organs that provide us with insights into mode of life. Here, we describe unique fossil preservation of an avian brain from the Volgograd region of European Russia. The brain of this Melovatka bird is similar in shape and morphology to those of known fossil ornithurines (the lineage that includes living birds), such as the marine diving birds Hesperornis and Enaliornis, but documents a new stage in avian sensory evolution: acute nocturnal vision coupled with well-developed hearing and smell, developed by the Late Cretaceous (ca 90Myr ago). This fossil also provides insights into previous 'bird-like' brain reconstructions for the most basal avian Archaeopteryx--reduction of olfactory lobes (sense of smell) and enlargement of the hindbrain (cerebellum) occurred subsequent to Archaeopteryx in avian evolution, closer to the ornithurine lineage that comprises living birds. The Melovatka bird also suggests that brain enlargement in early avians was not correlated with the evolution of powered flight.

  16. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age.

    PubMed

    Leuchter, Russia Ha-Vinh; Gui, Laura; Poncet, Antoine; Hagmann, Cornelia; Lodygensky, Gregory Anton; Martin, Ernst; Koller, Brigitte; Darqué, Alexandra; Bucher, Hans Ulrich; Hüppi, Petra Susan

    2014-08-27

    Premature infants are at risk of developing encephalopathy of prematurity, which is associated with long-term neurodevelopmental delay. Erythropoietin was shown to be neuroprotective in experimental and retrospective clinical studies. To determine if there is an association between early high-dose recombinant human erythropoietin treatment in preterm infants and biomarkers of encephalopathy of prematurity on magnetic resonance imaging (MRI) at term-equivalent age. A total of 495 infants were included in a randomized, double-blind, placebo-controlled study conducted in Switzerland between 2005 and 2012. In a nonrandomized subset of 165 infants (n=77 erythropoietin; n=88 placebo), brain abnormalities were evaluated on MRI acquired at term-equivalent age. Participants were randomly assigned to receive recombinant human erythropoietin (3000 IU/kg; n=256) or placebo (n=239) intravenously before 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. The primary outcome of the trial, neurodevelopment at 24 months, has not yet been assessed. The secondary outcome, white matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method. The resulting white matter injury and gray matter injury scores were categorized as normal or abnormal according to thresholds established in the literature by correlation with neurodevelopmental outcome. At term-equivalent age, compared with untreated controls, fewer infants treated with recombinant human erythropoietin had abnormal scores for white matter injury (22% [17/77] vs 36% [32/88]; adjusted risk ratio [RR], 0.58; 95% CI, 0.35-0.96), white matter signal intensity (3% [2/77] vs 11% [10/88]; adjusted RR, 0.20; 95% CI, 0.05-0.90), periventricular white matter loss (18% [14/77] vs 33% [29/88]; adjusted RR, 0.53; 95% CI, 0.30-0.92), and gray matter injury (7% [5/77] vs 19% [17/88]; adjusted RR, 0.34; 95% CI, 0.13-0.89). In an analysis of secondary

  17. Predicting the probability of abnormal stimulated growth hormone response in children after radiotherapy for brain tumors.

    PubMed

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

    2012-11-15

    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. 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. 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%. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. How do plants enlarge? A balancing act; Final report

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

    Boyer, J.S.

    1996-12-31

    Cells of plants are surrounded by strong walls that prevent rupture from internal pressures that can be two or three times that of an automobile tire. In this way, the walls protect the cytoplasm. However, at the same time, the cells can enlarge as they grow. How this balancing act works and how it enlarges the plant were the subject of a recent conference at the University of Delaware in Lewes. The aim was to identify areas for future research that could explain the enlargement of whole plants. There is a large practical need to predict and modify plant enlargementmore » but the additional processes that overlie the molecular ones need to be integrated with the molecular information before a picture will emerge. How best to accomplish this involved input from cross-disciplinary areas in biomechanics, physics and engineering as well as molecular biology, biochemistry and ultrastructure.« less

  19. MRI as a tool to study brain structure from mouse models for mental retardation

    NASA Astrophysics Data System (ADS)

    Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

    1998-07-01

    Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

  20. Growth, Hypothalamic Function, and Brain Ventricle Size in Mentally Retarded Subjects

    ERIC Educational Resources Information Center

    Leisti, S.; Iianainen, M.

    1978-01-01

    To determine whether moderate enlargement of the third brain ventricle or the temporal horns of the lateral ventricles was associated with hypothalamic dysfunction, 15 mentally retarded Ss (ages 12-25 years) with such characteristics were studies. (DLS)

  1. Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities.

    PubMed

    Parent, Maxime J; Zimmer, Eduardo R; Shin, Monica; Kang, Min Su; Fonov, Vladimir S; Mathieu, Axel; Aliaga, Antonio; Kostikov, Alexey; Do Carmo, Sonia; Dea, Doris; Poirier, Judes; Soucy, Jean-Paul; Gauthier, Serge; Cuello, A Claudio; Rosa-Neto, Pedro

    2017-12-13

    Imaging biomarkers are frequently proposed as endpoints for clinical trials targeting brain amyloidosis in Alzheimer's disease (AD); however, the specific impact of amyloid-β (Aβ) aggregation on biomarker abnormalities remains elusive in AD. Using the McGill-R-Thy1-APP transgenic rat as a model of selective Aβ pathology, we characterized the longitudinal progression of abnormalities in biomarkers commonly used in AD research. Middle-aged (9-11 months) transgenic animals (both male and female) displayed mild spatial memory impairments and disrupted cingulate network connectivity measured by resting-state fMRI, even in the absence of hypometabolism (measured with PET [ 18 F]FDG) or detectable fibrillary amyloidosis (measured with PET [ 18 F]NAV4694). At more advanced ages (16-19 months), cognitive deficits progressed in conjunction with resting connectivity abnormalities; furthermore, hypometabolism, Aβ plaque accumulation, reduction of CSF Aβ 1-42 concentrations, and hippocampal atrophy (structural MRI) were detectable at this stage. The present results emphasize the early impact of Aβ on brain connectivity and support a framework in which persistent Aβ aggregation itself is sufficient to impose memory circuits dysfunction, which propagates to adjacent brain networks at later stages. SIGNIFICANCE STATEMENT The present study proposes a "back translation" of the Alzheimer pathological cascade concept from human to animals. We used the same set of Alzheimer imaging biomarkers typically used in large human cohorts and assessed their progression over time in a transgenic rat model, which allows for a finer spatial resolution not attainable with mice. Using this translational platform, we demonstrated that amyloid-β pathology recapitulates an Alzheimer-like profile of biomarker abnormalities even in the absence of other hallmarks of the disease such as neurofibrillary tangles and widespread neuronal losses. Copyright © 2017 Parent et al.

  2. Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities

    PubMed Central

    Parent, Maxime J.; Kang, Min Su; Mathieu, Axel; Aliaga, Antonio; Do Carmo, Sonia; Dea, Doris; Gauthier, Serge; Cuello, A. Claudio

    2017-01-01

    Imaging biomarkers are frequently proposed as endpoints for clinical trials targeting brain amyloidosis in Alzheimer's disease (AD); however, the specific impact of amyloid-β (Aβ) aggregation on biomarker abnormalities remains elusive in AD. Using the McGill-R-Thy1-APP transgenic rat as a model of selective Aβ pathology, we characterized the longitudinal progression of abnormalities in biomarkers commonly used in AD research. Middle-aged (9–11 months) transgenic animals (both male and female) displayed mild spatial memory impairments and disrupted cingulate network connectivity measured by resting-state fMRI, even in the absence of hypometabolism (measured with PET [18F]FDG) or detectable fibrillary amyloidosis (measured with PET [18F]NAV4694). At more advanced ages (16–19 months), cognitive deficits progressed in conjunction with resting connectivity abnormalities; furthermore, hypometabolism, Aβ plaque accumulation, reduction of CSF Aβ1-42 concentrations, and hippocampal atrophy (structural MRI) were detectable at this stage. The present results emphasize the early impact of Aβ on brain connectivity and support a framework in which persistent Aβ aggregation itself is sufficient to impose memory circuits dysfunction, which propagates to adjacent brain networks at later stages. SIGNIFICANCE STATEMENT The present study proposes a “back translation” of the Alzheimer pathological cascade concept from human to animals. We used the same set of Alzheimer imaging biomarkers typically used in large human cohorts and assessed their progression over time in a transgenic rat model, which allows for a finer spatial resolution not attainable with mice. Using this translational platform, we demonstrated that amyloid-β pathology recapitulates an Alzheimer-like profile of biomarker abnormalities even in the absence of other hallmarks of the disease such as neurofibrillary tangles and widespread neuronal losses. PMID:29097597

  3. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviors in aged mice.

    PubMed

    Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B

    2017-06-01

    The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation, and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviors. Using both Grhl3-knockout mice (Grhl3 -/- ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3 flox/flox ), they performed histological expression analyses and behavioral tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety, and stress. They found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain; however, aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviors suggestive of decreased fear and anxiety. They conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behavior or hyperactivity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 775-788, 2017. © 2017 Wiley Periodicals, Inc.

  4. The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities.

    PubMed

    Shevah, O; Kornreich, L; Galatzer, A; Laron, Z

    2005-12-01

    The correlation between the molecular defects of the GH receptor (R), psychosocial development and brain abnormalities were evaluated in 10 patients with Laron syndrome (LS), in whom all data were available. The findings revealed that the intelligence quotient (IQ) and abnormalities in the brain of the patients with LS differ with various molecular defects of the GH-receptor. The most severe mental deficits and brain pathology occurred in patients with 3, 5, 6 exon deletion. Patients with point mutations in exons 2, 4 and 7 presented various degrees of medium to mild CNS abnormalities that correlated with the IQ. Notably, the patient with the E180 splice mutation in exon 6 had a normal IQ, which fits the report on normal IQ in a large Ecuadorian cohort with the same mutation. This is the first report to support a correlation between IQ, brain abnormalities and localization of the molecular defects in the GH-R gene. As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.

  5. Progressive Retinal Nerve Fiber Layer Atrophy Associated With Enlarging Peripapillary Pit.

    PubMed

    Lee, Eun Ji; Kim, Tae-Woo

    2017-02-01

    To report a case in which progressive retinal nerve fiber layer (RNFL) atrophy was observed along with enlargement of the peripapillary pit. A 34-year-old male was diagnosed with primary open-angle glaucoma and followed up for 4 years with regular ophthalmic examinations. Both eyes were myopic (-10 D, OD and -10.5 D, OS), and untreated intraocular pressures were 18 mm Hg (OD) and 16 mm Hg (OS). A subtle depression of the superotemporal peripapillary area was deepened and emerged as a peripapillary pit during the follow-up period. With the enlargement of the peripapillary pit, a RNFL defect at the location of pit widened and thinned continuously. The enlargement of the pit was documented by the spectral-domain optical coherence tomography posterior pole scanning. Progressive RNFL atrophy was observed with enlargement of the peripapillary pit. The finding suggests that tensile stress derived from the scleral stretching may have significant influence on the integrity of the RNFL.

  6. Calcium localization and tipburn development in lettuce leaves during early enlargement

    NASA Technical Reports Server (NTRS)

    Barta, D. J.; Tibbitts, T. W.

    2000-01-01

    Tissue concentrations of Ca, Mg, and K were determined across immature leaves of lettuce (Lactuca sativa L. 'Buttercrunch') at different stages of enlargement using electron microprobe x-ray analysis. The analysis was with a wavelength dispersive spectrometer to permit detection of low concentrations of Ca. Patterns of mineral accumulation in immature leaves that were exposed were compared to patterns of accumulation in leaves that were enclosed within a developing head. The leaves developing without enclosure were free to transpire and developed normally whereas leaves developing with enclosure were restricted in transpiration and developed an injury that was characteristic of Ca deficiency. In the exposed leaves, Ca concentrations increased from an average of 1.0 to 2.1 mg g-1 dry weight (DW) as the leaves enlarged from 5 to 30 mm in length. In the enclosed leaves, Ca concentrations decreased from 1.0 to 0.7 mg g-1 DW as the leaves enlarged from 5 to 30 mm in length. At the tips of these enclosed leaves a larger decrease was found, from 0.9 to 0.3 mg g-1 DW during enlargement. Necrotic injury first became apparent in this tip area when the concentration was approximate to 0.4 mg g-1 DW. Magnesium concentrations across the exposed leaves were similar to concentrations across the enclosed leaves, and did not change with enlargement. Magnesium concentrations averaged 3.5. mg g-1 DW in both enclosed and exposed leaves during enlargement from 5 to 30 mm. In both exposed and enclosed leaves, K concentrations increased during enlargement from 40 to approximate to 60 mg g-1 DW. Potassium concentrations were highest toward the leaf apex and upper margin where injury symptoms occurred, and this may have enhanced injury development. This research documents the critical low levels of Ca (0.2 to 0.4 mg g-1 DW) that can occur in enclosed leaves of plants and which apparently leads to the marginal apex necrosis of developing leaves seen frequently on lettuce and other crops.

  7. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

    PubMed Central

    Nakao, Kazuhito; Nakazawa, Kazu

    2014-01-01

    In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The “paradoxically” high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception. PMID:25018691

  8. Genetic control of postnatal human brain growth

    PubMed Central

    van Dyck, Laura I.; Morrow, Eric M.

    2017-01-01

    Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

  9. Regional brain volumes and cognition in childhood epilepsy: does size really matter?

    PubMed

    Zelko, Frank A; Pardoe, Heath R; Blackstone, Sarah R; Jackson, Graeme D; Berg, Anne T

    2014-05-01

    Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function. The study sample included 108 individuals with uncomplicated non-syndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls. Participants received a standardized cognitive battery. Whole brain T1-weighted MRI was obtained and volumes analyzed with FreeSurfer (TM). Total brain volume (TBV) was significantly smaller in cases. After adjustment for TBV, cases had significantly larger regional grey matter volumes for total, frontal, parietal, and precentral cortex. Cases had poorer performance on neurocognitive indices of intelligence and variability of sustained attention. In cases, TBV showed small associations with intellectual indices of verbal and perceptual ability, working memory, and overall IQ. In controls, TBV showed medium associations with working memory and variability of sustained attention. In both groups, small associations were seen between some TBV-adjusted regional brain volumes and neurocognitive indices, but not in a consistent pattern. Brain volume differences did not account for cognitive differences between the groups. Patients with uncomplicated NSE have smaller brains than controls but areas of relative grey matter enlargement. That this relative regional enlargement occurs in the context of poorer overall neurocognitive functioning suggests that it is not adaptive. However, the lack of consistent associations between case-control differences in brain volumes and cognitive functioning suggests that brain volumes have limited explanatory value for cognitive functioning in childhood epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.

    PubMed

    Chandana, Sreenivasa R; Behen, Michael E; Juhász, Csaba; Muzik, Otto; Rothermel, Robert D; Mangner, Thomas J; Chakraborty, Pulak K; Chugani, Harry T; Chugani, Diane C

    2005-01-01

    The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

  11. Abnormal brain MRI signals in the splenium of the corpus callosum, basal ganglia and internal capsule in a suspected case with tuberculous meningitis.

    PubMed

    Hirotani, Makoto; Yabe, Ichiro; Hamada, Shinsuke; Tsuji, Sachiko; Kikuchi, Seiji; Sasaki, Hidenao

    2007-01-01

    A 34-year-old man visited the hospital with chief complaints of headache, fever, and disturbance of consciousness. In view of his clinical condition, the course of the disease, and results of examination, he was diagnosed with viral meningitis and treated accordingly. However, his clinical condition worsened, and MRI revealed abnormal signals in the splenium of the corpus callosum, in the basal ganglia and in the internal capsule, as well as the presence of severe inflammation in the base of the brain. Since he had a high ADA level in the cerebrospinal fluid and was consequently suspected to have tuberculous meningitis, he was placed on antitubercular agents. Then, his clinical condition began to improve. Additional steroid pulse therapy further improved his condition, and abnormal signals in the splenium of the corpus callosum and the basal ganglia resolved. This valuable case suggests that an immune mechanism contributed to the occurrence of central nervous system symptoms associated with tuberculous meningitis.

  12. Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

    PubMed

    Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

    2017-07-01

    Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

  13. A review of MRI findings in schizophrenia

    PubMed Central

    Shenton, Martha E.; Dickey, Chandlee C.; Frumin, Melissa; McCarley, Robert W.

    2009-01-01

    After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin,E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described ‘dementia praecox’ and the ‘ schizophrenias’, were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82–120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137–147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the

  14. Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia.

    PubMed

    Del Bene, Victor A; Foxe, John J; Ross, Lars A; Krakowski, Menahem I; Czobor, Pal; De Sanctis, Pierfilippo

    2016-01-01

    Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of-interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals.

  15. Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.

    PubMed

    Kim, Dae Hyun; Grodstein, Francine; Newman, Anne B; Chaves, Paulo H M; Odden, Michelle C; Klein, Ronald; Sarnak, Mark J; Lipsitz, Lewis A

    2015-09-01

    To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). Community. Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication. © 2015, Copyright the Authors Journal compilation © 2015

  16. Body-enlarging effect of royal jelly in a non-holometabolous insect species, Gryllus bimaculatus

    PubMed Central

    Miyashita, Atsushi; Kizaki, Hayato; Sekimizu, Kazuhisa; Kaito, Chikara

    2016-01-01

    ABSTRACT Honeybee royal jelly is reported to have body-enlarging effects in holometabolous insects such as the honeybee, fly and silkmoth, but its effect in non-holometabolous insect species has not yet been examined. The present study confirmed the body-enlarging effect in silkmoths fed an artificial diet instead of mulberry leaves used in the previous literature. Administration of honeybee royal jelly to silkmoth from early larval stage increased the size of female pupae and adult moths, but not larvae (at the late larval stage) or male pupae. We further examined the body-enlarging effect of royal jelly in a non-holometabolous species, the two-spotted cricket Gryllus bimaculatus, which belongs to the evolutionarily primitive group Polyneoptera. Administration of royal jelly to G. bimaculatus from its early nymph stage enlarged both males and females at the mid-nymph and adult stages. In the cricket, the body parts were uniformly enlarged in both males and females; whereas the enlarged female silkmoths had swollen abdomens. Administration of royal jelly increased the number, but not the size, of eggs loaded in the abdomen of silkmoth females. In addition, fat body cells were enlarged by royal jelly in the silkmoth, but not in the cricket. These findings suggest that the body-enlarging effect of royal jelly is common in non-holometabolous species, G. bimaculatus, but it acts in a different manner than in holometabolous species. PMID:27185266

  17. Body-enlarging effect of royal jelly in a non-holometabolous insect species, Gryllus bimaculatus.

    PubMed

    Miyashita, Atsushi; Kizaki, Hayato; Sekimizu, Kazuhisa; Kaito, Chikara

    2016-06-15

    Honeybee royal jelly is reported to have body-enlarging effects in holometabolous insects such as the honeybee, fly and silkmoth, but its effect in non-holometabolous insect species has not yet been examined. The present study confirmed the body-enlarging effect in silkmoths fed an artificial diet instead of mulberry leaves used in the previous literature. Administration of honeybee royal jelly to silkmoth from early larval stage increased the size of female pupae and adult moths, but not larvae (at the late larval stage) or male pupae. We further examined the body-enlarging effect of royal jelly in a non-holometabolous species, the two-spotted cricket Gryllus bimaculatus, which belongs to the evolutionarily primitive group Polyneoptera. Administration of royal jelly to G. bimaculatus from its early nymph stage enlarged both males and females at the mid-nymph and adult stages. In the cricket, the body parts were uniformly enlarged in both males and females; whereas the enlarged female silkmoths had swollen abdomens. Administration of royal jelly increased the number, but not the size, of eggs loaded in the abdomen of silkmoth females. In addition, fat body cells were enlarged by royal jelly in the silkmoth, but not in the cricket. These findings suggest that the body-enlarging effect of royal jelly is common in non-holometabolous species, G. bimaculatus, but it acts in a different manner than in holometabolous species. © 2016. Published by The Company of Biologists Ltd.

  18. The autistic brain in the context of normal neurodevelopment.

    PubMed

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

    2015-01-01

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

  19. Detecting gait abnormalities after concussion or mild traumatic brain injury: A systematic review of single-task, dual-task, and complex gait.

    PubMed

    Fino, Peter C; Parrington, Lucy; Pitt, Will; Martini, Douglas N; Chesnutt, James C; Chou, Li-Shan; King, Laurie A

    2018-05-01

    While a growing number of studies have investigated the effects of concussion or mild traumatic brain injury (mTBI) on gait, many studies use different experimental paradigms and outcome measures. The path for translating experimental studies for objective clinical assessments of gait is unclear. This review asked 2 questions: 1) is gait abnormal after concussion/mTBI, and 2) what gait paradigms (single-task, dual-task, complex gait) detect abnormalities after concussion. Data sources included MEDLINE/PubMed, Scopus, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) accessed on March 14, 2017. Original research articles reporting gait outcomes in people with concussion or mTBI were included. Studies of moderate, severe, or unspecified TBI, and studies without a comparator were excluded. After screening 233 articles, 38 studies were included and assigned to one or more sections based on the protocol and reported outcomes. Twenty-six articles reported single-task simple gait outcomes, 24 reported dual-task simple gait outcomes, 21 reported single-task complex gait outcomes, and 10 reported dual-task complex gait outcomes. Overall, this review provides evidence for two conclusions: 1) gait is abnormal acutely after concussion/mTBI but generally resolves over time; and 2) the inconsistency of findings, small sample sizes, and small number of studies examining homogenous measures at the same time-period post-concussion highlight the need for replication across independent populations and investigators. Future research should concentrate on dual-task and complex gait tasks, as they showed promise for detecting abnormal locomotor function outside of the acute timeframe. Additionally, studies should provide detailed demographic and clinical characteristics to enable more refined comparisons across studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

    PubMed Central

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

    2012-01-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

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

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

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Wu Shengjie; Chemaitilly, Wassim

    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),more » 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.« less

  2. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome

    PubMed Central

    Holtzman, David M.; Santucci, Daniela; Kilbridge, Joshua; Chua-Couzens, Jane; Fontana, David J.; Daniels, Scott E.; Johnson, Randolph M.; Chen, Karen; Sun, Yuling; Carlson, Elaine; Alleva, Enrico; Epstein, Charles J.; Mobley, William C.

    1996-01-01

    To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain. PMID:8917591

  3. Cortical gyrification is abnormal in children with prenatal alcohol exposure.

    PubMed

    Hendrickson, Timothy J; Mueller, Bryon A; Sowell, Elizabeth R; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Wozniak, Jeffrey R

    2017-01-01

    Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined. Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure. Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ). Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.

  4. Salivary glands abnormalities in oculo-auriculo-vertebral spectrum.

    PubMed

    Brotto, Davide; Manara, Renzo; Vio, Stefania; Ghiselli, Sara; Cantone, Elena; Mardari, Rodica; Toldo, Irene; Stritoni, Valentina; Castiglione, Alessandro; Lovo, Elisa; Trevisi, Patrizia; Bovo, Roberto; Martini, Alessandro

    2018-01-01

    Feeding and swallowing impairment are present in up to 80% of oculo-auriculo-vertebral spectrum (OAVS) patients. Salivary gland abnormalities have been reported in OAVS patients but their rate, features, and relationship with phenotype severity have yet to be defined. Parotid and submandibular salivary gland hypo/aplasia was evaluated on head MRI of 25 OAVS patients (16 with severe phenotype, Goldenhar syndrome) and 11 controls. All controls disclosed normal salivary glands. Abnormal parotid glands were found exclusively ipsilateral to facial microsomia in 21/25 OAVS patients (84%, aplasia in six patients) and showed no association with phenotype severity (14/16 patients with Goldenhar phenotype vs 7/9 patients with milder phenotype, p = 0.6). Submandibular salivary gland hypoplasia was detected in six OAVS patients, all with concomitant ipsilateral severe involvement of the parotid gland (p < 0.001). Submandibular salivary gland hypoplasia was associated to Goldenhar phenotype (p < 0.05). Parotid gland abnormalities were associated with ipsilateral fifth (p < 0.001) and seventh cranial nerve (p = 0.001) abnormalities. No association was found between parotid gland anomaly and ipsilateral internal carotid artery, inner ear, brain, eye, or spine abnormalities (p > 0.6). Salivary gland abnormalities are strikingly common in OAVS. Their detection might help the management of OAVS-associated swallowing and feeding impairment.

  5. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    PubMed Central

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  6. Neurodevelopmental origins of abnormal cortical morphology in dissociative identity disorder.

    PubMed

    Reinders, A A T S; Chalavi, S; Schlumpf, Y R; Vissia, E M; Nijenhuis, E R S; Jäncke, L; Veltman, D J; Ecker, C

    2018-02-01

    To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of gaining important novel insights into the underlying neurobiological mechanisms mediating DID. This study included 32 female patients with DID and 43 matched healthy controls. Between-group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex-wise approach. Whole-brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization. Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found. In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Salivary gland enlargement during oesophageal stricture dilatation.

    PubMed Central

    Martin, D.

    1980-01-01

    A case of recurrent salivary gland enlargement occurring during fibreoptic oesophagoscopy and oesophageal stricture dilatation with Eder-Puestow dilators is described. The genesis of this condition is discussed and its transient and usually benign nature emphasized. Images Fig. 1 PMID:7393809

  8. Tumescent power liposuction in the treatment of the enlarged male breast.

    PubMed

    Boni, Roland

    2006-01-01

    Tumescent power liposuction is widely used on various parts of the body for minimal-access lipectomy. The undesired fat deposits are injected with tumescence fluid containing saline, epinephrine, bicarbonate and lidocaine; the latter is used as the only source of pain control. The fat is then removed using vibrating microcannulas. To evaluate the value of tumescent power liposuction in the treatment of the enlarged male breast. 38 male patients aged 23-64 years (mean age 39.8 +/- 9.7 years) with enlarged breasts were enrolled in the study. In 32 patients, breasts were enlarged due to fat tissue, and the ductal glands were not palpable (pseudogynecomastia). In 6 patients, the ductal glands were enlarged (gynecomastia). All patients were treated with tumescent liposuction over a 2-year period using a single entry site from the axillary fossa. Both fat as well as ductal and stromal tissue were removed by microcannulas. None of the patients had early postoperative complications of infection, hematoma or seroma. There were no treatment-induced asymmetries, contour deformities or irregularities. No open excision or skin reduction procedures were required. Tumescent liposuction using a single entry site in the axillary fossa is a minimally invasive technique to treat enlarged male breasts. Both fat (pseudogynecomastia in adipose patients) as well as ductal and stromal tissue (in gynecomastia) can be removed with tumescent liposuction, resulting in a high level of patient satisfaction. Copyright 2006 S. Karger AG, Basel.

  9. Levator Muscle Enlargement in Thyroid Eye Disease-Related Upper Eyelid Retraction.

    PubMed

    Davies, Michael J; Dolman, Peter J

    To identify levator palpebrae superioris enlargement in thyroid eye disease (TED)-related upper eyelid retraction (ULR). Retrospective case-control. Subjects included 50 consecutive patients with unilateral thyroid eye disease-related ULR ≥ 2 mm and no previous eyelid surgery. The contralateral side was used as control. Clinical information was recorded from charts. CT scans were assessed by investigators blinded to the clinical data. A prediction of retracted side was made based on CT scan appearance and on basis of measured levator palpebrae superioris cross-sectional area at 2 defined points. Statistical analysis determined correlation between levator palpebrae superioris size and presence of ULR. The study was approved by the institutional ethics committee. Side with ULR predicted from CT scan review in over 85% of cases. Mean cross-sectional area of levator palpebrae superioris on retracted side was significantly larger than nonretracted side at 2 separate sites. Levator palpebrae superioris area was larger on retracted side compared with nonretracted side in over 85% of subjects. More than 30% of subjects had no enlargement of other extraocular muscles. Only 6% of patients had enlargement of the ipsilateral inferior rectus muscle. Levator palpebrae superioris enlargement from inflammation or scar is a factor in thyroid eye disease-related ULR. Upper eyelid retraction can be predicted from CT scan appearance in over 85% of cases. Ipsilateral inferior rectus enlargement is rare. Levator palpebrae superioris is the most commonly targeted muscle in thyroid eye disease.

  10. BRAIN ABNORMALITIES IN YOUNG ADULTS AT GENETIC RISK FOR AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A CROSS-SECTIONAL STUDY

    PubMed Central

    Reiman, Eric M.; Quiroz, Yakeel T.; Fleisher, Adam S.; Chen, Kewei; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Fagan, Anne M.; Shah, Aarti R.; Alvarez, Sergio; Arbelaez, Andrés; Giraldo, Margarita; Acosta-Baena, Natalia; Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.; Tirado, Victoria; Munoz, Claudia; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B.S.; Kosik, Kenneth S.; Tariot, Pierre N.; Lopera, Francisco

    2013-01-01

    Summary Background We previously detected functional brain imaging abnormalities in young adults at genetic risk for late-onset Alzheimer’s disease (AD). Here, we sought to characterize structural and functional magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarker abnormalities in young adults at risk for autosomal dominant early-onset AD. Biomarker measurements were characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the world’s largest known autosomal dominant early-onset AD kindred, more than two decades before the carriers’ estimated median age of 44 at the onset of mild cognitive impairment (MCI) and before their estimated age of 28 at the onset of amyloid-β (Aβ) plaque deposition. Methods Biomarker data for this cross-sectional study were acquired in Antioquia, Colombia between July and August, 2010. Forty-four participants from the Colombian Alzheimer’s Prevention Initiative (API) Registry had structural MRIs, functional MRIs during associative memory encoding/novel viewing and control tasks, and cognitive assessments. They included 20 mutation carriers and 24 non-carriers, who were cognitively normal, 18-26 years old and matched for their gender, age, and educational level. Twenty of the participants, including 10 mutation carriers and 10 non-carriers, had lumbar punctures and venipunctures. Primary outcome measures included task-dependent hippocampal/parahippocampal activations and precuneus/posterior cingulate deactivations, regional gray matter reductions, CSF Aβ1-42, total tau and phospho-tau181 levels, and plasma Aβ1-42 levels and Aβ1-42/Aβ1-40 ratios. Structural and functional MRI data were compared using automated brain mapping algorithms and AD-related search regions. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings The mutation carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological

  11. Relationship between intracranial internal carotid artery calcification and enlarged cerebral perivascular space.

    PubMed

    Tao, Xiao-Xiao; Li, Ge-Fei; Wu, Yi-Lan; Liu, Yi-Sheng; Zhao, Ying; Shi, Yan-Hui; Zhuang, Mei-Ting; Hou, Tian-Yu; Zhao, Rong; Liu, Feng-Di; Wang, Xue-Mei; Shen, Ying; Cui, Guo-Hong; Su, Jing-Jing; Chen, Wei; Tang, Xue-Mei; Sun, Ji; Liu, Jian-Ren

    2017-06-01

    The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.

  12. Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

    PubMed Central

    Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

    2017-01-01

    Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

  13. Multidimensional analysis of the abnormal neural oscillations associated with lexical processing in schizophrenia.

    PubMed

    Xu, Tingting; Stephane, Massoud; Parhi, Keshab K

    2013-04-01

    The neural mechanisms of language abnormalities, the core symptoms in schizophrenia, remain unclear. In this study, a new experimental paradigm, combining magnetoencephalography (MEG) techniques and machine intelligence methodologies, was designed to gain knowledge about the frequency, brain location, and time of occurrence of the neural oscillations that are associated with lexical processing in schizophrenia. The 248-channel MEG recordings were obtained from 12 patients with schizophrenia and 10 healthy controls, during a lexical processing task, where the patients discriminated correct from incorrect lexical stimuli that were visually presented. Event-related desynchronization/synchronization (ERD/ERS) was computed along the frequency, time, and space dimensions combined, that resulted in a large spectral-spatial-temporal ERD/ERS feature set. Machine intelligence techniques were then applied to select a small subset of oscillation patterns that are abnormal in patients with schizophrenia, according to their discriminating power in patient and control classification. Patients with schizophrenia showed abnormal ERD/ERS patterns during both lexical encoding and post-encoding periods. The top-ranked features were located at the occipital and left frontal-temporal areas, and covered a wide frequency range, including δ (1-4 Hz), α (8-12 Hz), β (12-32 Hz), and γ (32-48 Hz) bands. These top features could discriminate the patient group from the control group with 90.91% high accuracy, which demonstrates significant brain oscillation abnormalities in patients with schizophrenia at the specific frequency, time, and brain location indicated by these top features. As neural oscillation abnormality may be due to the mechanisms of the disease, the spectral, spatial, and temporal content of the discriminating features can offer useful information for helping understand the physiological basis of the language disorder in schizophrenia, as well as the pathology of the

  14. L-DOPS corrects neurochemical abnormalities in a Menkes disease mouse model

    PubMed Central

    Donsante, Anthony; Sullivan, Patricia; Goldstein, David S.; Brinster, Lauren R.; Kaler, Stephen G.

    2012-01-01

    Objective Menkes disease is a lethal neurodegenerative disorder of infancy caused by mutations in a copper-transporting ATPase gene, ATP7A. Among its multiple cellular tasks, ATP7A transfers copper to dopamine-beta-hydroxylase (DBH) within the lumen of the Golgi network or secretory granules, catalyzing the conversion of dopamine to norepinephrine. In a well-established mouse model of Menkes disease, mottled-brindled, we tested whether systemic administration of L-threo-dihydroxyphenylserine (L-DOPS), a drug used successfully to treat autosomal recessive norepinephrine deficiency, would improve brain neurochemical abnormalities and neuropathology. Methods At 8, 10, and 12 days of age, wild type and mo-br mice received intraperi-toneal injections of 200μg/g body weight of L-DOPS, or mock solution. Five hours after the final injection, the mice were euthanized and brains removed. We measured catecholamine metabolites affected by DBH via high-performance liquid chromatography with electrochemical detection, and assessed brain histopathology. Results Compared to mock-treated controls, mo-br mice that received intraperitoneal L-DOPS showed significant increases in brain norepinephrine (P<0.001) and its deaminated metabolite, dihydroxyphenylglycol (DHPG, P<0.05). The ratio of a non-beta-hydroxylated metabolite in the catecholamine biosynthetic pathway, dihydroxyphenylacetic acid, to the beta-hydroxylated metabolite, dihydroxyphenylglycol, improved equivalently to results obtained previously with brain-directed ATP7A gene therapy (P<0.01). However, L-DOPS treatment did not arrest global brain pathology or improve somatic growth, as gene therapy had. Interpretation We conclude that 1) L-DOPS crosses the blood-brain barrier in mo-br mice and corrects brain neurochemical abnormalities, 2) norepinephrine deficiency is not the cause of neurodegeneration in mo-br mice, and 3) L-DOPS treatment may ameliorate noradrenergic hypofunction in Menkes disease. PMID:23224983

  15. Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage.

    PubMed

    Takahashi, Takehiro; Asano, Yoshihide; Oka, Tomonori; Miyagaki, Tomomitsu; Tamaki, Zenshiro; Nonaka, Senshu; Sato, Shinichi

    2016-02-01

    We report a 39-year-old man referred to our facility with linear sclerotic lesions along the several Blaschko's lines of the scalp. A year before the referral, he had had an episode of brain hemorrhage, although there was no evidence of vascular malformation or any other risk factors of brain hemorrhage for his young age. On the diagnosis of scleroderma en coup de sabre, prednisolone intake was initiated, and the skin lesions were well controlled. However, in the course of our follow up, he had another episode of brain hemorrhage, again without any evidence of cerebral vascular abnormalities. Organic intracranial abnormalities in this disease are well-documented, but there have been few reports on comorbid recurrent brain hemorrhages. We herein discuss the possible relationship of the skin lesions with the brain hemorrhages in our case, taking notice of the implication of developmental abnormalities behind these apparently independent phenomena inside and outside the cranium. © 2015 Japanese Dermatological Association.

  16. Abnormal regional activity and functional connectivity in resting-state brain networks associated with etiology confirmed unilateral pulsatile tinnitus in the early stage of disease.

    PubMed

    Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

    2017-03-01

    Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging (rs-fMRI) using analyses of the regional activity and functional connectivity (FC) of the networks in the brain. This study was designed to demonstrate the functional network alterations in the patients with pulsatile tinnitus (PT). In this study, we recruited 45 patients with unilateral PT in the early stage of disease (less than 48 months of disease duration) and 45 normal controls. We used regional homogeneity (ReHo) and seed-based FC computational methods to reveal resting-state brain activity features associated with pulsatile tinnitus. Compared with healthy controls, PT patients showed regional abnormalities mainly in the left middle occipital gyrus (MOG), posterior cingulate gyrus (PCC), precuneus and right anterior insula (AI). When these regions were defined as seeds, we demonstrated widespread modification of interaction between the auditory and non-auditory networks. The auditory network was positively connected with the cognitive control network (CCN), which may associate with tinnitus related distress. Both altered regional activity and changed FC were found in the visual network. The modification of interactions of higher order networks were mainly found in the DMN, CCN and limbic networks. Functional connectivity between the left MOG and left parahippocampal gyrus could also be an index to reflect the disease duration. This study helped us gain a better understanding of the characteristics of neural network modifications in patients with pulsatile tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Left globus pallidus abnormality in never-medicated patients with schizophrenia

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

    Early, T.S.; Reiman, E.M.; Raichle, M.E.

    1987-01-01

    Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5more » patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found.« less

  18. The D153del Mutation in GNB3 Gene Causes Tissue Specific Signalling Patterns and an Abnormal Renal Morphology in Rge Chickens

    PubMed Central

    Tummala, Hemanth; Fleming, Stewart; Hocking, Paul M.; Wehner, Daniel; Naseem, Zahid; Ali, Manir; Inglehearn, Christopher F.; Zhelev, Nikolai; Lester, Douglas H.

    2011-01-01

    Background The GNB3 gene is expressed in cone but not rod photoreceptors of vertebrates, where it acts as the β transducin subunit in the colour visual transduction process. A naturally occurring mutation ‘D153del’ in the GNB3 gene causes the recessively inherited blinding phenotype retinopathy globe enlarged (rge) disease in chickens. GNB3 is however also expressed in most other vertebrate tissues suggesting that the D153del mutation may exert pathological effects that outlie from eye. Principal Findings Recombinant studies in COS-7 cells that were transfected with normal and mutant recombinant GNB3 constructs and subjected to cycloheximide chase showed that the mutant GNB3d protein had a much shorter half life compared to normal GNB3. GNB3 codes for the Gβ3 protein subunit that, together with different Gγ and Gα subunits, activates and regulates phosphorylation cascades in different tissues. As expected, the relative levels of cGMP and cAMP secondary messengers and their activated kinases such as MAPK, AKT and GRK2 were also found to be altered significantly in a tissue specific manner in rge chickens. Histochemical analysis on kidney tissue sections, from rge homozygous affected chickens, showed the chickens had enlargement of the glomerular capsule, causing glomerulomegaly and tubulointerstitial inflammation whereas other tissues (brain, heart, liver, pancreas) were unaffected. Significance These findings confirm that the D153del mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3 signalling causes reduced phosphorylation activity of ERK2 and AKT leading to severe pathological phenotypes such as blindness and renal abnormalities in rge chickens. PMID:21887213

  19. Brain morphology in children with nevoid basal cell carcinoma syndrome.

    PubMed

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

    2017-04-01

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

  20. Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain.

    PubMed

    Ribeiro, Rafael Teixeira; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Leipnitz, Guilhian; de Oliveira, Francine Hehn; Seminotti, Bianca; Wajner, Moacir

    2018-04-01

    Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2',7'-dichloroflurescein-DCFH-oxidation), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione-GSH) and sulfhydryl content in the cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in the cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in the cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked significant vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.

  1. Evidence for brain glucose dysregulation in Alzheimer's disease.

    PubMed

    An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

    2018-03-01

    It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

  2. Dental and maxillofacial abnormalities in long-term survivors of childhood cancer: effects of treatment with chemotherapy and radiation to the head and neck

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

    Jaffe, N.; Toth, B.B.; Hoar, R.E.

    1984-06-01

    Sixty-eight long-term survivors of childhood cancer were evaluated for dental and maxillofacial abnormalities. Forty-five patients had received maxillofacial radiation for lymphoma, leukemia, rhabdomyosarcoma, and miscellaneous tumors. Forty-three of the 45 patients and the remaining 23 who had not received maxillofacial radiation also received chemotherapy. Dental and maxillofacial abnormalities were detected in 37 of the 45 (82%) radiated patients. Dental abnormalities comprised foreshortening and blunting of roots, incomplete calcification, premature closure of apices, delayed or arrested tooth development, and caries. Maxillofacial abnormalities comprised trismus, abnormal occlusal relationships, and facial deformities. The abnormalities were more severe in those patients who received radiationmore » at an earlier age and at higher dosages. Possible chemotherapeutic effects in five of 23 patients who received treatment for tumors located outside the head and neck region comprised acquired amelogenesis imperfecta, microdontia of bicuspid teeth, and a tendency toward thinning of roots with an enlarged pulp chamber. Dental and maxillofacial abnormalities should be recognized as a major consequence of maxillofacial radiation in long-term survivors of childhood cancer, and attempts to minimize or eliminate such sequelae should involve an effective interaction between radiation therapists, and medical and dental oncologists.« less

  3. Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations.

    PubMed

    Liddle, Elizabeth B; Price, Darren; Palaniyappan, Lena; Brookes, Matthew J; Robson, Siân E; Hall, Emma L; Morris, Peter G; Liddle, Peter F

    2016-04-01

    Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long-range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  4. Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations

    PubMed Central

    Liddle, Elizabeth B.; Price, Darren; Palaniyappan, Lena; Brookes, Matthew J.; Robson, Siân E.; Hall, Emma L.; Morris, Peter G.

    2016-01-01

    Abstract Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long‐range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. Hum Brain Mapp 37:1361‐1374, 2016. © 2016 Wiley Periodicals, Inc. PMID:26853904

  5. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Parvaz, Muhammad A; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

    2012-10-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. © 2012 Published 2012. This article is a US Government work and is in the public domain in the USA.

  6. MRI anatomy of schizophrenia.

    PubMed

    McCarley, R W; Wible, C G; Frumin, M; Hirayasu, Y; Levitt, J J; Fischer, I A; Shenton, M E

    1999-05-01

    Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer-reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a "two-hit" model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical

  7. Abnormal Functional Connectivity in Autism Spectrum Disorders during Face Processing

    ERIC Educational Resources Information Center

    Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

    2008-01-01

    Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…

  8. Integrative assessment of brain function in PTSD: brain stability and working memory.

    PubMed

    Veltmeyer, Melinda D; McFarlane, Alexander C; Bryant, Richard A; Mayo, Therese; Gordon, Evian; Clark, C Richard

    2006-03-01

    Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

  9. The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses

    PubMed Central

    2010-01-01

    Background Proton Magnetic Resonance (MR) Spectroscopy (MRS) is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS) in MRS data analysis has been explored. Results This work presents the INTERPRET DSS version 3.0, analysing the improvements made from its first release in 2002. Version 3.0 is aimed to be a program that 1st, can be easily used with any new case from any MR scanner manufacturer and 2nd, improves the initial analysis capabilities of the first version. The main improvements are an embedded database, user accounts, more diagnostic discrimination capabilities and the possibility to analyse data acquired under additional data acquisition conditions. Other improvements include a customisable graphical user interface (GUI). Most diagnostic problems included have been addressed through a pattern-recognition based approach, in which classifiers based on linear discriminant analysis (LDA) were trained and tested. Conclusions The INTERPRET DSS 3.0 allows radiologists, medical physicists, biochemists or, generally speaking, any person with a minimum knowledge of what an MR spectrum is, to enter their own SV raw data, acquired at 1.5 T, and to analyse them. The system is expected to help in the categorisation of MR Spectra from abnormal brain masses. PMID:21114820

  10. SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography.

    PubMed

    Abu-Judeh, H H; Parker, R; Singh, M; el-Zeftawy, H; Atay, S; Kumar, M; Naddaf, S; Aleksic, S; Abdel-Dayem, H M

    1999-06-01

    We present SPET brain perfusion findings in 32 patients who suffered mild traumatic brain injury without loss of consciousness and normal computed tomography. None of the patients had previous traumatic brain injury, CVA, HIV, psychiatric disorders or a history of alcohol or drug abuse. Their ages ranged from 11 to 61 years (mean = 42). The study was performed in 20 patients (62%) within 3 months of the date of injury and in 12 (38%) patients more than 3 months post-injury. Nineteen patients (60%) were involved in a motor vehicle accident, 10 patients (31%) sustained a fall and three patients (9%) received a blow to the head. The most common complaints were headaches in 26 patients (81%), memory deficits in 15 (47%), dizziness in 13 (41%) and sleep disorders in eight (25%). The studies were acquired approximately 2 h after an intravenous injection of 740 MBq (20.0 mCi) of 99Tcm-HMPAO. All images were acquired on a triple-headed gamma camera. The data were displayed on a 10-grade colour scale, with 2-pixel thickness (7.4 mm), and were reviewed blind to the patient's history of symptoms. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in the cortex or basal ganglia less than 70%, or less than 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. The results show that 13 (41%) had normal studies and 19 (59%) were abnormal (13 studies performed within 3 months of the date of injury and six studies performed more than 3 months post-injury). Analysis of the abnormal studies revealed that 17 showed 48 focal lesions and two showed diffuse supratentorial hypoperfusion (one from each of the early and delayed imaging groups). The 12 abnormal studies performed early had 37 focal lesions and averaged 3.1 lesions per patient, whereas there was a reduction to--an average of 2.2 lesions per patient in the five studies (total 11 lesions) performed more than 3 months post-injury. In the

  11. Merit Pay and Job Enlargement as Reforms: Incentives, Implementation, and Teacher Response.

    ERIC Educational Resources Information Center

    Firestone, William A.

    1991-01-01

    Based on intensive case studies of two school districts, this study compared two teacher work reforms: merit pay and job enlargement. Interviews with 64 teachers and 53 administrators, supplemented by over 1,300 survey responses, indicate the efficacy of each approach and the potential advantages of job enlargement. (SLD)

  12. Subclinical ultrasonographic abnormalities of the suspensory ligament branches in National Hunt racehorses.

    PubMed

    Fairburn, A J; Busschers, E; Barr, A R S

    2017-07-01

    Suspensory ligament branch (SLB) desmopathy is a common cause of lameness and an important cause of lost training in the Thoroughbred racing industry. Studies have assessed the impact of insertional injuries of the SLB on the careers of flat racehorses and established the prevalence of subclinical ultrasonographic SLB abnormalities in this population, but little work has investigated SLB injury in National Hunt (NH) racehorses. To investigate the prevalence of subclinical ultrasonographic SLB abnormalities in NH racehorses with no clinical signs or history of SLB injury and to establish the cross-sectional area (CSA) of SLBs in this population. Cross-sectional study using data collected from horses on an NH yard. Ultrasonographic examination of forelimb SLBs in 62 horses on a single NH yard was performed. Images were graded according to a previously reported system. CSA measurements were obtained from transverse images. Nineteen of 62 horses had at least one SLB with grade 2 ultrasonographic abnormalities. Grade 2 ultrasonographic abnormalities occurred more frequently in the medial than the lateral SLB (P = 0.05). The medial SLB insertional CSA was significantly larger (P<0.001) than that of the lateral SLB. Length of time on the yard (and therefore available veterinary history) is variable in this population. One in three NH racehorses without history or clinical signs of SLB injury had at least one SLB with a grade 2 ultrasonographic abnormality. The medial branch was over-represented. The medial SLB insertional CSA is larger than the lateral and thus comparison with the corresponding branch in the contralateral limb is recommended to avoid misdiagnosis of medial SLB enlargement. © 2016 EVJ Ltd.

  13. Progressive brain atrophy in patients with chronic neuropsychiatric symptoms after mild traumatic brain injury: a preliminary study.

    PubMed

    Ross, David E; Ochs, Alfred L; Seabaugh, Jan M; Demark, Michael F; Shrader, Carole R; Marwitz, Jennifer H; Havranek, Michael D

    2012-01-01

    NeuroQuant® is a recently developed, FDA-approved software program for measuring brain MRI volume in clinical settings. The aims of this study were as follows: (1) to examine the test-retest reliability of NeuroQuant®; (2) to test the hypothesis that patients with mild traumatic brain injury (TBI) would have abnormally rapid progressive brain atrophy; and (3) to test the hypothesis that progressive brain atrophy in patients with mild TBI would be associated with vocational outcome. Sixteen patients with mild TBI were compared to 20 normal controls. Vocational outcome was assessed with the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS). NeuroQuant® showed high test-re-test reliability. Patients had abnormally rapid progressive atrophy in several brain regions and the rate of atrophy was associated with inability to return to work. NeuroQuant®, is a reliable and valid method for assessing the anatomic effects of TBI. Progression of atrophy may continue for years after injury, even in patients with mild TBI.

  14. Mutations in α-Tubulin Cause Abnormal Neuronal Migration in Mice and Lissencephaly in Humans

    PubMed Central

    Keays, David A.; Tian, Guoling; Poirier, Karine; Huang, Guo-Jen; Siebold, Christian; Cleak, James; Oliver, Peter L.; Fray, Martin; Harvey, Robert J.; Molnár, Zoltán; Piñon, Maria C.; Dear, Neil; Valdar, William; Brown, Steve D.M.; Davies, Kay E.; Rawlins, J. Nicholas P.; Cowan, Nicholas J.; Nolan, Patrick; Chelly, Jamel; Flint, Jonathan

    2007-01-01

    Summary The development of the mammalian brain is dependent on extensive neuronal migration. Mutations in mice and humans that affect neuronal migration result in abnormal lamination of brain structures with associated behavioral deficits. Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)-induced mouse mutant with abnormalities in the laminar architecture of the hippocampus and cortex, accompanied by impaired neuronal migration. We show that the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of α-1 tubulin (Tuba1) and affects tubulin heterodimer formation. Phenotypic similarity with existing mouse models of lissencephaly led us to screen a cohort of patients with developmental brain anomalies. We identified two patients with de novo mutations in TUBA3, the human homolog of Tuba1. This study demonstrates the utility of ENU mutagenesis in the mouse as a means to discover the basis of human neurodevelopmental disorders. PMID:17218254

  15. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    PubMed

    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

  16. Grey matter abnormalities in children and adolescents with functional neurological symptom disorder.

    PubMed

    Kozlowska, Kasia; Griffiths, Kristi R; Foster, Sheryl L; Linton, James; Williams, Leanne M; Korgaonkar, Mayuresh S

    2017-01-01

    Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure . These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10-18 years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p < 0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder.

  17. Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).

    PubMed

    Wozniak, Jeffrey R; Mueller, Bryon A; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Sowell, Elizabeth R

    2017-10-01

    Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

  18. Brainstem abnormalities and vestibular nerve enhancement in acute neuroborreliosis.

    PubMed

    Farshad-Amacker, Nadja A; Scheffel, Hans; Frauenfelder, Thomas; Alkadhi, Hatem

    2013-12-21

    Borreliosis is a widely distributed disease. Neuroborreliosis may present with unspecific symptoms and signs and often remains difficult to diagnose in patients with central nervous system symptoms, particularly if the pathognomonic erythema chronica migrans does not develop or is missed. Thus, vigilance is mandatory in cases with atypical presentation of the disease and with potentially severe consequences if not recognized early. We present a patient with neuroborreliosis demonstrating brain stem and vestibular nerve abnormalities on magnetic resonance imaging. A 28-year-old Caucasian female presented with headaches, neck stiffness, weight loss, nausea, tremor, and gait disturbance. Magnetic resonance imaging showed T2-weighted hyperintense signal alterations in the pons and in the vestibular nerves as well as bilateral post-contrast enhancement of the vestibular nerves. Serologic testing of the cerebrospinal fluid revealed the diagnosis of neuroborreliosis. Patients infected with neuroborreliosis may present with unspecific neurologic symptoms and magnetic resonance imaging as a noninvasive imaging tool showing signal abnormalities in the brain stem and nerve root enhancement may help in establishing the diagnosis.

  19. Infratemporal fossa fat enlargement in chronic maxillary atelectasis.

    PubMed

    Kohn, Jocelyne C; Rootman, Daniel B; Xu, Dongdong; Goldberg, Robert A

    2013-08-01

    To describe the radiographic findings in chronic maxillary atelectasis and analyse the volume changes of the affected maxillary sinus, orbit, nasal vault and infratemporal fossa. Case series of all patients with diagnosis of chronic maxillary atelectasis presenting between January 2000 and August 2012 who underwent full oculoplastic and orbital evaluation including standardised photography and CT or MRI. Two-dimensional imaging features and volumetric changes were assessed. Affected and unaffected sides were compared. Demographic data, clinical presentation, Hertel measurements, photographic and radiological findings were analysed. 22 patients (64% men) met the inclusion criteria. Mean relative enophthalmos was 2.1 mm and mean hypoglobus was 1.8 mm. The most common radiographic findings were sinus opacification (91%), uncinate process retraction/middle meatus increase (91%), orbit enlargement (100%), ipsilateral septum deviation (64%) and infratemporal fossa fat enlargement (100%). Infratemporal fossa fat area and volume were significantly larger in the affected side (p<0.01). Additionally, ipsilateral orbit (p<0.01) and nasal vault volume (p<0.01) were similarly increased. Maxillary sinus volume correlated significantly only with infratemporal fossa fat enlargement (p<0.05). There is a significant increase in the infratemporal fossa fat, nasal and orbital volume corresponding to a decrease in maxillary sinus size in chronic maxillary atelectasis. Chronic maxillary atelectasis is associated with redistribution of volume between the maxillary sinus and the surrounding infratemporal fossa, orbit and nasal cavity.

  20. Pattern analysis of nerve enlargement using ultrasonography in chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Jang, Jae Hong; Cho, Charles S; Yang, Kyung-Sook; Seok, Hung Youl; Kim, Byung-Jo

    2014-09-01

    Focal nerve enlargement is a characteristic finding in chronic inflammatory demyelinating polyneuropathy (CIDP). We performed this study to assess the distribution of nerve enlargement through ultrasonographic examination of peripheral nerves and to correlate the ultrasonographic findings with clinical features. To compare the ultrasonographic features of 10 subjects with CIDP with those of 18 healthy controls, we bilaterally measured the cross-sectional areas (CSA) of the vagus, brachial plexus, musculocutaneous, median, ulnar, radial, sciatic, tibial, common peroneal, and sural nerves. We also analyzed correlations between CSAs and various clinical and electrophysiological features. Mean CSAs were significantly larger in CIDP patients than controls, especially at proximal and non-entrapment sites. CSAs were significantly correlated with muscle strength at initial presentation, but not at the time of ultrasonography. The CSAs of the median and ulnar nerves at the mid-forearm, tibial nerve at 7 cm proximal to the medial malleolus, and sural nerve correlated with the nerve conduction velocity of the corresponding region. Ultrasonography revealed widely distributed nerve enlargement, especially in proximal regions and non-entrapment sites, in patients with CIDP compared with healthy controls. Nerve enlargement correlated well with the electrophysiologic function of the nerve, but not current clinical status. Pattern analysis of nerve enlargement using ultrasonography is a supportive tool in the diagnosis of CIDP. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

    PubMed Central

    Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

    2015-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

  2. Cerebellar abnormalities typical of methylmercury poisoning in a fledged saltmarsh sparrow, Ammodramus caudacutus.

    PubMed

    Scoville, Sheila A; Lane, Oksana P

    2013-05-01

    A fledged, 12-15 day-old saltmarsh sparrow, Ammodramus caudacutus, was collected from an accidental kill on Cinder Island, Long Island, NY, USA. The sparrow was assessed for feather mercury levels and the brain analyzed for cerebellar abnormalities by microscopic examination. In humans, fetal Minamata disease is caused by maternal ingestion of mercury. It is characterized by disrupted and disordered cerebellar neuronal migration in the fetus or infant. Results from this sparrow show cerebellar abnormalities typical of Minamata disease. It is the first known avian or mammalian specimen taken from the wild to show the abnormalities typical of the human fetal syndrome.

  3. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    PubMed Central

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  4. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data

    PubMed Central

    Edwin Thanarajah, Sharmili; Han, Cheol E.; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J.

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder. PMID:27445870

  5. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data.

    PubMed

    Edwin Thanarajah, Sharmili; Han, Cheol E; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal-frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder.

  6. Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

    PubMed

    Shi, Lei; Hu, Enzhi; Wang, Zhenbo; Liu, Jiewei; Li, Jin; Li, Ming; Chen, Hua; Yu, Chunshui; Jiang, Tianzi; Su, Bing

    2017-02-01

    Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

  7. Sexually dimorphic white matter geometry abnormalities in adolescent onset schizophrenia.

    PubMed

    Savadjiev, P; Whitford, T J; Hough, M E; Clemm von Hohenberg, C; Bouix, S; Westin, C-F; Shenton, M E; Crow, T J; James, A C; Kubicki, M

    2014-05-01

    The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

  8. On the Application of Quantitative EEG for Characterizing Autistic Brain: A Systematic Review

    PubMed Central

    Billeci, Lucia; Sicca, Federico; Maharatna, Koushik; Apicella, Fabio; Narzisi, Antonio; Campatelli, Giulia; Calderoni, Sara; Pioggia, Giovanni; Muratori, Filippo

    2013-01-01

    Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies. PMID:23935579

  9. Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and insulin resistance.

    PubMed

    Reutrakul, Sirimon; Hathout, Eba H; Janner, Donald; Hara, Manami; Donfack, Joseph; Bass, Joseph; Refetoff, Samuel

    2004-04-01

    The proband, a 9-year-old Hispanic female, presented with hair loss, strabismus, and weight gain. On magnetic resonance imaging (MRI) she was found to have severe primary hypothyroidism and a large pituitary mass. In addition, acanthosis nigricans, obesity, and hyperinsulinism were observed. Findings were similar in three of four siblings. Thyroid peroxidase antibodies were detected in the father and three of four siblings. Although all family members were obese, and hyperinsulinemia with high proinsulin and C-peptide was found in all except one sibling, only the mother and one child had overt type 2 diabetes mellitus. Because of the unusual association of autoimmune thyroid disease, insulin resistance and obesity rather than insulin deficiency, we searched for possible genetic abnormalities. The HLA haplotypes did not cosegregate with autoimmune thyroid disease or insulin resistance. Mutational analysis of known obesity genes was done. Leptin was not deficient, and sequencing of the proband's DNA showed no mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma(2), PPAR-alpha or melanocortin 4 receptor genes. Maternally inherited diabetes and deafness was ruled out since no mutations were found in mitochondria DNA. Insulin receptor antibodies were not detected. In conclusion, the remarkably high incidence of childhood autoimmune hypothyroidism, pituitary enlargement, insulin resistance and obesity in this family is not linked to known HLA types or known gene defects.

  10. Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

    PubMed

    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.

  11. Penile enlargement: from medication to surgery.

    PubMed

    Nugteren, Helena M; Balkema, G T; Pascal, A L; Schultz, W C M Weijmar; Nijman, J M; van Driel, M F

    2010-01-01

    Penis lengthening pills, stretch apparatus, vacuum pumps, silicone injections, and lengthening and thickening operations are available for men who worry about their penis size. Surgery is thus far the only proven scientific method for penile enlargement. In this article, we consider patient selection, outcome evaluation, and techniques applied. In our view, sexological counseling and detailed explanation of risks and complications are mandatory before any operative intervention.

  12. Routine transesophageal echocardiography for the diagnosis of aortic disruption in trauma patients without enlarged mediastinum.

    PubMed

    Vignon, P; Lagrange, P; Boncoeur, M P; Francois, B; Gastinne, H; Lang, R M

    1996-03-01

    To assess the value of routine transesophageal echocardiography (TEE) in diagnosing traumatic disruption of the aorta (TDA) in trauma patients presenting without enlarged mediastinum on chest x-ray films. Prospective study. TEE was routinely performed to exclude the presence of TDA in patients who sustained severe trauma secondary to abrupt deceleration collisions and presented with an upper mediastinum of fewer than 8 cm on supine chest x-ray films. Patients were divided into two groups according to the presence (group I) or absence (group II) of mediastinal hematoma diagnosed during TEE examination. Radiographic signs regarded as indicators of the presence of TDA were evaluated in both groups. Among the 40 consecutive patients studied, TEE demonstrated two cases of TDA associated with a mediastinal hematoma that were confirmed by both aortography and surgery. One of the patients had a normal mediastinum on presentation chest x-ray films, and the other only exhibited a blurred aortic knob. Radiographic mediastinal abnormalities suggestive of TDA were observed in 13 patients, but chest x-ray films were unremarkable in 12 patients. Twenty patients had multiple rib fractures. The frequency of chest radiographic abnormalities was not significantly higher in group I (n = 6) when compared with group II patients (n = 34). TEE examination demonstrated a normal thoracic aorta in 35 patients and was nondiagnostic in 3 patients (normal aortography). TEE should be routinely performed in victims of violent deceleration collisions, even in patients presenting apparently normal mediastinum on supine chest radiography.

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

    PubMed

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

    2001-10-01

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

  14. L-threo-dihydroxyphenylserine corrects neurochemical abnormalities in a Menkes disease mouse model.

    PubMed

    Donsante, Anthony; Sullivan, Patricia; Goldstein, David S; Brinster, Lauren R; Kaler, Stephen G

    2013-02-01

    Menkes disease is a lethal neurodegenerative disorder of infancy caused by mutations in a copper-transporting adenosine triphosphatase gene, ATP7A. Among its multiple cellular tasks, ATP7A transfers copper to dopamine beta hydroxylase (DBH) within the lumen of the Golgi network or secretory granules, catalyzing the conversion of dopamine to norepinephrine. In a well-established mouse model of Menkes disease, mottled-brindled (mo-br), we tested whether systemic administration of L-threo-dihydroxyphenylserine (L-DOPS), a drug used successfully to treat autosomal recessive norepinephrine deficiency, would improve brain neurochemical abnormalities and neuropathology. At 8, 10, and 12 days of age, wild-type and mo-br mice received intraperitoneal injections of 200μg/g body weight of L-DOPS, or mock solution. Five hours after the final injection, the mice were euthanized, and brains were removed. We measured catecholamine metabolites affected by DBH via high-performance liquid chromatography with electrochemical detection, and assessed brain histopathology. Compared to mock-treated controls, mo-br mice that received intraperitoneal L-DOPS showed significant increases in brain norepinephrine (p < 0.001) and its deaminated metabolite, dihydroxyphenylglycol (p < 0.05). The ratio of a non-beta-hydroxylated metabolite in the catecholamine biosynthetic pathway, dihydroxyphenylacetic acid, to the beta-hydroxylated metabolite, dihydroxyphenylglycol, improved equivalently to results obtained previously with brain-directed ATP7A gene therapy (p < 0.01). However, L-DOPS treatment did not arrest global brain pathology or improve somatic growth, as gene therapy had. We conclude that (1) L-DOPS crosses the blood-brain barrier in mo-br mice and corrects brain neurochemical abnormalities, (2) norepinephrine deficiency is not the cause of neurodegeneration in mo-br mice, and (3) L-DOPS treatment may ameliorate noradrenergic hypofunction in Menkes disease. Copyright © 2012 American

  15. Spleen and liver enlargement in a patient with rheumatoid arthritis.

    PubMed

    Bedoya, María Eugenia; Ceccato, Federico; Paira, Sergio

    2015-01-01

    We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. Sensorineural hearing loss in a pediatric population: association of congenital cytomegalovirus infection with intracranial abnormalities.

    PubMed

    Kimani, Jane W; Buchman, Craig A; Booker, Jessica K; Huang, Benjamin Y; Castillo, Mauricio; Powell, Cynthia M; Weck, Karen E

    2010-10-01

    To examine the incidence of congenital cytomegalovirus (CMV) infection relative to common genetic etiologies of hearing loss in a pediatric population with sensorineural hearing loss (SNHL), and to characterize intracranial radiological abnormalities in patients with CMV-associated hearing loss. Retrospective study. Academic tertiary care center. A total of 112 pediatric patients with confirmed SNHL. The association of congenital CMV infection status with abnormal brain magnetic resonance imaging (MRI) scans and the frequencies of congenital CMV infection, gap junction β-2 (GJB2) mutations, and the mitochondrial DNA (mtDNA) 1555A>G mutation in children with SNHL. Of 109 patients, 11 (10%) had positive results for CMV DNA; 10 of the 11 had normal GJB2 sequence and had negative test results for the mtDNA 1555A>G mutation. Brain MRI scans for 97 patients demonstrated a higher proportion of abnormalities in patients with positive CMV test results (80%) compared with those with no detectable CMV DNA (33%) (P = .006). GJB2 mutations and the mtDNA 1555A>G mutation were seen in 10 of 88 patients (11%) and 1 of 97 patients (1%) with SNHL, respectively. The presence of brain abnormalities in most patients with congenital CMV infection suggests that neurological damage in otherwise asymptomatic patients may not be limited to SNHL. Congenital CMV infection accounted for a significant proportion of patients with SNHL, with an incidence rate comparable with that of GJB2-related SNHL.

  17. Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

    PubMed Central

    McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

    2013-01-01

    Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

  18. ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones.

    PubMed

    Masuda, Takamasa; Wada, Yasutaka; Kawamura, Satoru

    2016-03-01

    Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria.

  19. Isolated amygdala enlargement in temporal lobe epilepsy: A systematic review.

    PubMed

    Beh, S M Jessica; Cook, Mark J; D'Souza, Wendyl J

    2016-07-01

    The objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies. PubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords 'amygdala enlargement', 'epilepsy', and 'seizures' in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included. Of 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small samples of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67-100% vs. 26-47%), and they have an excellent response to antiepileptic drugs (81.8%-100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls. Reliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests

  20. Job enlargement and mechanical exposure variability in cyclic assembly work.

    PubMed

    Möller, Therése; Mathiassen, Svend Erik; Franzon, Helena; Kihlberg, Steve

    2004-01-15

    Cyclic assembly work is known to imply a high risk for musculoskeletal disorders. To have operators rotate between work tasks is believed to be one way of decreasing this risk, since it is expected to increase variation in mechanical and psychological exposures (physical and mental loads). This assumption was investigated by assessing mechanical exposure variability in three assembly tasks in an electronics assembly plant, each on a separate workstation, as well as in a 'job enlargement' scenario combining all three stations. Five experienced operators worked for 1 h on each station. Data on upper trapezius and forearm extensor muscle activity were obtained by means of electromyography (EMG), and working postures of the head and upper arms were assessed by inclinometry. The cycle-to-cycle variance of parameters representing the three exposure dimensions: level, frequency and duration was estimated using ANOVA algorithms for each workstation separately as well as for a balanced combination of all three. For a particular station, the variability of trapezius EMG activity levels relative to the mean was higher than for extensor EMG: between-cycles coefficients of variation (CV) about 0.15 and 0.10, respectively. A similar relationship between CV applied to the parameter describing frequency of EMG activity. Except for head inclination levels, the between-cycles CV was larger for posture parameters than for EMG. The between-cycles variance increased up to six fold in the job enlargement scenario, as compared to working at only one station. The difference in mean exposure between workstations was larger for trapezius EMG parameters than for forearm extensor EMG and postures, and hence the effect of job enlargement on exposure variability was more pronounced for the trapezius. For some stations, job enlargement even implied less cycle-to-cycle variability in forearm extensor EMG parameters than working at that station only. Whether the changes in exposure variability

  1. Brain size and thermoregulation during the evolution of the genus Homo.

    PubMed

    Naya, Daniel E; Naya, Hugo; Lessa, Enrique P

    2016-01-01

    Several hypotheses have been proposed to explain the evolution of an energetically costly brain in the genus Homo. Some of these hypotheses are based on the correlation between climatic factors and brain size recorded for this genus during the last millions of years. In this study, we propose a complementary climatic hypothesis that is based on the mechanistic connection between temperature, thermoregulation, and size of internal organs in endothermic species. We hypothesized that global cooling during the last 3.2 my may have imposed an increased energy expenditure for thermoregulation, which in the case of hominids could represent a driver for the evolution of an expanded brain, or at least, it could imply the relaxation of a negative selection pressure acting upon this costly organ. To test this idea, here we (1) assess variation in the energetic costs of thermoregulation and brain maintenance for the last 3.2 my, and (2) evaluate the relationship between Earth temperature and brain maintenance cost for the same period, taking into account the effects of body mass and fossil age. We found that: (1) the energetic cost associated with brain enlargement represents an important fraction (between 47.5% and 82.5%) of the increase in energy needed for thermoregulation; (2) fossil age is a better predictor of brain maintenance cost than Earth temperature, suggesting that (at least) another factor correlated with time was more relevant than ambient temperature in brain size evolution; and (3) there is a significant negative correlation between the energetic cost of brain and Earth temperature, even after accounting for the effect of body mass and fossil age. Thus, our results expand the current energetic framework for the study of brain size evolution in our lineage by suggesting that a fall in Earth temperature during the last millions of years may have facilitated brain enlargement. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism

    NASA Astrophysics Data System (ADS)

    Shou, Guofa; Mosconi, Matthew W.; Wang, Jun; Ethridge, Lauren E.; Sweeney, John A.; Ding, Lei

    2017-08-01

    Objective. Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. Approach. Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. Main results. Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. Significance. Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.

  3. Whole-brain functional connectivity identification of functional dyspepsia.

    PubMed

    Nan, Jiaofen; Liu, Jixin; Li, Guoying; Xiong, Shiwei; Yan, Xuemei; Yin, Qing; Zeng, Fang; von Deneen, Karen M; Liang, Fanrong; Gong, Qiyong; Qin, Wei; Tian, Jie

    2013-01-01

    Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.

  4. Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

    2011-02-14

    Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. The maternal brain and its plasticity in humans

    PubMed Central

    Kim, Pilyoung; Strathearn, Lane; Swain, James E.

    2015-01-01

    Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

  6. Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder.

    PubMed

    Piras, I S; Haapanen, L; Napolioni, V; Sacco, R; Van de Water, J; Persico, A M

    2014-05-01

    Circulating 45 and 62kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N=355), their unaffected siblings (N=142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62kDa antibodies are correlated with autism severity: the 45kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62kDa autoAb in the child is significantly associated with presence of the 39 and/or 73kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Abnormal brain structure in youth who commit homicide

    PubMed Central

    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

  8. Abnormal brain structure in youth who commit homicide.

    PubMed

    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

    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. 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). 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. Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses.

  9. Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats.

    PubMed

    Nakajima, Yuko; Horiuchi, Yutaka; Kamata, Hiroshi; Yukawa, Masayoshi; Kuwabara, Masato; Tsubokawa, Takashi

    2010-07-01

    Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

  10. Evolution of complex higher brain centers and behaviors: behavioral correlates of mushroom body elaboration in insects.

    PubMed

    Farris, Sarah M

    2013-01-01

    Large, complex higher brain centers have evolved many times independently within the vertebrates, but the selective pressures driving these acquisitions have been difficult to pinpoint. It is well established that sensory brain centers become larger and more structurally complex to accommodate processing of a particularly important sensory modality. When higher brain centers such as the cerebral cortex become greatly expanded in a particular lineage, it is likely to support the coordination and execution of more complex behaviors, such as those that require flexibility, learning, and social interaction, in response to selective pressures that made these new behaviors advantageous. Vertebrate studies have established a link between complex behaviors, particularly those associated with sociality, and evolutionary expansions of telencephalic higher brain centers. Enlarged higher brain centers have convergently evolved in groups such as the insects, in which multimodal integration and learning and memory centers called the mushroom bodies have become greatly elaborated in at least four independent lineages. Is it possible that similar selective pressures acting on equivalent behavioral outputs drove the evolution of large higher brain centers in all bilaterians? Sociality has greatly impacted brain evolution in vertebrates such as primates, but it has not been a major driver of higher brain center enlargement in insects. However, feeding behaviors requiring flexibility and learning are associated with large higher brain centers in both phyla. Selection for the ability to support behavioral flexibility appears to be a common thread underlying the evolution of large higher brain centers, but the precise nature of these computations and behaviors may vary. © 2013 S. Karger AG, Basel.

  11. Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder.

    PubMed

    Yuksel, C; Du, F; Ravichandran, C; Goldbach, J R; Thida, T; Lin, P; Dora, B; Gelda, J; O'Connor, L; Sehovic, S; Gruber, S; Ongur, D; Cohen, B M

    2015-09-01

    Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.

  12. Longitudinal MRI Study of Cortical Development through Early Childhood in Autism

    PubMed Central

    Schumann, C.M.; Bloss, C.S.; Barnes, C. Carter; Wideman, G.M.; Carper, R.A.; Akshoomoff, N.; Pierce, K.; Hagler, D.; Schork, N.; Lord, C.; Courchesne, E.

    2010-01-01

    Cross-sectional MRI studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however this has never been confirmed by a longitudinal study. We carried out the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent utilizing structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of Autistic Disorder at ~48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter was significantly enlarged in toddlers with Autistic Disorder, with the most severe enlargement occurring in frontal, temporal and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with Autistic Disorder that was mainly characterized by a quadratic age effect. Females with Autistic Disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers in order to determine the underlying neuropathological processes causing the onset of autistic symptoms. PMID:20335478

  13. Selective mutism and abnormal electroencephalography (EEG) tracings.

    PubMed

    Politi, Keren; Kivity, Sara; Goldberg-Stern, Hadassa; Halevi, Ayelet; Shuper, Avinoam

    2011-11-01

    Epileptic discharges are not considered a part of the clinical picture of selective mutism, and electroencephalography is generally not recommended in its work-up. This report describes 6 children with selective mutism who were found to have a history of epilepsy and abnormal interictal or subclinical electroencephalography recordings. Two of them had benign epilepsy of childhood with centro-temporal spikes. The mutism was not related in time to the presence of active seizures. While seizures could be controlled in all children by medications, the mutism resolved only in 1. Although the discharges could be coincidental, they might represent a co-morbidity of selective mutism or even play a role in its pathogenesis. Selective mutism should be listed among the psychiatric disorders that may be associated with electroencephalographic abnormalities. It can probably be regarded as a symptom of a more complicated organic brain disorder.

  14. Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects

    NASA Astrophysics Data System (ADS)

    Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

    2017-08-01

    Objective. Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. Approach. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. Main results. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. Significance. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

  15. Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects.

    PubMed

    Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

    2017-08-01

    Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

  16. Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases.

    PubMed

    Wheeler, Richard; Turner, Robert D; Bailey, Richard G; Salamaga, Bartłomiej; Mesnage, Stéphane; Mohamad, Sharifah A S; Hayhurst, Emma J; Horsburgh, Malcolm; Hobbs, Jamie K; Foster, Simon J

    2015-07-28

    Most bacterial cells are enclosed in a single macromolecule of the cell wall polymer, peptidoglycan, which is required for shape determination and maintenance of viability, while peptidoglycan biosynthesis is an important antibiotic target. It is hypothesized that cellular enlargement requires regional expansion of the cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that are together required for cell enlargement and correct cellular morphology of Staphylococcus aureus, demonstrating the overall importance of this enzyme activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the explanation of the observed morphological defects in terms of the mechanical and biochemical properties of peptidoglycan. It was shown that cells lacking groups of these hydrolases have increased surface stiffness and, in the absence of SagB, substantially increased glycan chain length. This indicates that, beyond their established roles (for example in cell separation), some hydrolases enable cellular enlargement by making peptidoglycan easier to stretch, providing the first direct evidence demonstrating that cellular enlargement occurs via modulation of the mechanical properties of peptidoglycan. Understanding bacterial growth and division is a fundamental problem, and knowledge in this area underlies the treatment of many infectious diseases. Almost all bacteria are surrounded by a macromolecule of peptidoglycan that encloses the cell and maintains shape, and bacterial cells must increase the size of this molecule in order to enlarge themselves. This requires not only the insertion of new peptidoglycan monomers, a process targeted by antibiotics, including penicillin, but also breakage of existing bonds, a potentially hazardous activity for the cell. Using Staphylococcus aureus, we have identified a set of enzymes that are critical for cellular enlargement. We

  17. Quantification of abnormal intracranial pressure waves and isotope cisternography for diagnosis of occult communicating hydrocephalus

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

    Cardoso, E.R.; Piatek, D.; Del Bigio, M.R.

    1989-01-01

    Nineteen consecutive patients with suspected occult communicating hydrocephalus were investigated by means of clinical evaluation, neuropsychological testing, isotope cisternography, computed tomography scanning, and continuous intracranial pressure monitoring. Semi-quantitative grading systems were used in the evaluation of the clinical, neuropsychological, and cisternographic assessments. Clinical examination, neuropsychological testing, and computed tomography scanning were repeated 3 months after ventriculoperitoneal shunting. All patients showed abnormal intracranial pressure waves and all improved after shunting. There was close correlation between number, peak, and pulse pressures of B waves and the mean intracranial pressure. However, quantification of B waves by means of number, frequency, and amplitude didmore » not help in predicting the degree of clinical improvement postshunting. The most sensitive predictor of favorable response to shunting was enlargement of the temporal horns on computed tomography scan. Furthermore, the size of temporal horns correlated with mean intracranial pressure. There was no correlation between abnormalities on isotope cisternography and clinical improvement.« less

  18. Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

    PubMed

    Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

    2016-10-01

    This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

  19. The universe, life, and intelligence (Sixth enlarged edition)

    NASA Astrophysics Data System (ADS)

    Shklovskii, Iosif Samuilovich

    This classic work examines the possibility of the existence of life (including intelligent life) on other planetary systems. This enlarged edition includes essays on the search for extraterrestrial civilizations and the possibility of communication with intelligent beings on other planets.

  20. Features of Brain MRI in Dogs with Treated and Untreated Mucopolysaccharidosis Type I

    PubMed Central

    Vite, Charles H; Nestrasil, Igor; Mlikotic, Anton; Jens, Jackie K; Snella, Elizabeth M; Gross, William; Shapiro, Elsa G; Kovac, Victor; Provenzale, James M; Chen, Steven; Le, Steven Q; Kan, Shih-hsin; Banakar, Shida; Wang, Raymond Y; Haskins, Mark E; Ellinwood, N Matthew; Dickson, Patricia I

    2013-01-01

    The mucopolysaccharidosis type I (MPS I) dog model has been important in the development of therapies for human patients. We treated dogs with enzyme replacement therapy (ERT) by various approaches. Dogs assessed included untreated MPS I dogs, heterozygous carrier dogs, and MPS I dogs treated with intravenous ERT as adults (beginning at age 13 to 16 mo), intrathecal and intravenous ERT as adults (beginning at age 13 to 16 mo), or intrathecal ERT as juveniles (beginning at age 4 mo). We then characterized the neuroimaging findings of 32 of these dogs (age, 12 to 30 mo). Whole and midsagittal volumes of the corpus callosum, measured from brain MRI, were significantly smaller in affected dogs compared with unaffected heterozygotes. Corpus callosum volumes in dogs that were treated with intrathecal ERT from 4 mo until 21 mo of age were indistinguishable from those of age-matched carrier controls. Dogs with MPS I showed cerebral ventricular enlargement and cortical atrophy as early as 12 mo of age. Ventricular enlargement was greater in untreated MPS I dogs than in age-matched dogs treated with intrathecal ERT as juveniles or adults. However, treated dogs still showed some ventricular enlargement or cortical atrophy (or both). Understanding the progression of neuroimaging findings in dogs with MPS I and their response to brain-directed therapy may improve preclinical studies for new human-directed therapies. In particular, corpus callosum volumes may be useful quantitative neuroimaging markers for MPS-related brain disease and its response to therapy. PMID:23582423

  1. Digital atlas of fetal brain MRI.

    PubMed

    Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

    2010-02-01

    Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

  2. Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

    PubMed Central

    Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

    2015-01-01

    Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

  3. Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns

    PubMed Central

    Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

    2013-01-01

    Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

  4. Hypoplastic uterus and clitoris enlargement in Swyer syndrome.

    PubMed

    Hétu, Valérie; Caron, Evelyne; Francoeur, Diane

    2010-02-01

    Swyer syndrome is associated with absent testicular differentiation in a 46XY phenotypic female. A 17-year-old female presented with primary amenorrhea and 46XY karyotype. Breast and pubic hair development were Tanner 2, and clitoral enlargement was noted. Magnetic resonance imaging revealed a hypoplastic uterus and 2 "normal ovaries." Serum follicle-stimulating hormone and luteinizing hormone were elevated. Testosterone and androstenedione were in the female range. Dehydroepiandrosterone sulfate was slightly elevated. Laparoscopic bilateral gonadectomy was performed. Pathology reports showed bilateral microscopic benign hilar cell tumors. The diagnosis was a real puzzle for the clinicians because of the association of clitoral hypertrophy without hirsutism, female internal genitalia, and a 46XY karyotype. Clitoral enlargement can be explained by transient androgen secretion by the hilar cells found in the resected gonads. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  5. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    ERIC Educational Resources Information Center

    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.…

  6. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

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

    USDA-ARS?s Scientific Manuscript database

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

  8. Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

    PubMed

    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.

  9. Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

    PubMed

    Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

    2016-07-01

    Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

  10. Cortical enlargement in autism is associated with a functional VNTR in the monoamine oxidase A gene.

    PubMed

    Davis, Lea K; Hazlett, Heather C; Librant, Amy L; Nopoulos, Peggy; Sheffield, Val C; Piven, Joesph; Wassink, Thomas H

    2008-10-05

    Monoamine oxidase A (MAOA) is an enzyme expressed in the brain that metabolizes dopamine, norepinephrine, epinephrine, and serotonin. Abnormalities of serotonin neurotransmission have long been implicated in the psychopathology of autism. A polymorphism exists within the promoter region of the MAOA gene that influences MAOA expression levels so that "low activity" alleles are associated with increased neurotransmitter levels in the brain. Individuals with autism often exhibit elevated serotonin levels. Additional studies indicate that the "low activity" allele may be associated with lower IQ and more severe autistic symptoms. In this study we genotyped the MAOA promoter polymorphism in a group of 29 males (age 2-3 years) with autism and a group of 39 healthy pediatric controls for whom brain MRI data was available. We found a consistent association between the "low activity" allele and larger brain volumes for regions of the cortex in children with autism but not in controls. We did not find evidence for over-transmission of the "low activity" allele in a separate sample of 114 affected sib pair families. Nor did we find any unknown SNPs in yet another sample of 96 probands. Future studies will determine if there is a more severe clinical phenotype associated with both the "low activity" genotype and the larger brain volumes in our sample.

  11. Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

    PubMed

    Crespo, Iris; Santos, Alicia; Gómez-Ansón, Beatriz; López-Mourelo, Olga; Pires, Patricia; Vives-Gilabert, Yolanda; Webb, Susan M; Resmini, Eugenia

    2016-09-01

    Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety.

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

    PubMed

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

    2017-01-01

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

  13. Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation.

    PubMed

    Mizumura, Sunao; Kumita, Shin-ichiro; Cho, Keiichi; Ishihara, Makiko; Nakajo, Hidenobu; Toba, Masahiro; Kumazaki, Tatsuo

    2003-06-01

    Through visual assessment by three-dimensional (3D) brain image analysis methods using stereotactic brain coordinates system, such as three-dimensional stereotactic surface projections and statistical parametric mapping, it is difficult to quantitatively assess anatomical information and the range of extent of an abnormal region. In this study, we devised a method to quantitatively assess local abnormal findings by segmenting a brain map according to anatomical structure. Through quantitative local abnormality assessment using this method, we studied the characteristics of distribution of reduced blood flow in cases with dementia of the Alzheimer type (DAT). Using twenty-five cases with DAT (mean age, 68.9 years old), all of whom were diagnosed as probable Alzheimer's disease based on NINCDS-ADRDA, we collected I-123 iodoamphetamine SPECT data. A 3D brain map using the 3D-SSP program was compared with the data of 20 cases in the control group, who age-matched the subject cases. To study local abnormalities on the 3D images, we divided the whole brain into 24 segments based on anatomical classification. We assessed the extent of an abnormal region in each segment (rate of the coordinates with a Z-value that exceeds the threshold value, in all coordinates within a segment), and severity (average Z-value of the coordinates with a Z-value that exceeds the threshold value). This method clarified orientation and expansion of reduced accumulation, through classifying stereotactic brain coordinates according to the anatomical structure. This method was considered useful for quantitatively grasping distribution abnormalities in the brain and changes in abnormality distribution.

  14. Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

    PubMed Central

    Provenzale, James M.; Nestrasil, Igor; Chen, Steven; Kan, Shih-hsin; Le, Steven Q.; Jens, Jacqueline K.; Snella, Elizabeth M.; Vondrak, Kristen N.; Yee, Jennifer K.; Vite, Charles H.; Elashoff, David; Duan, Lewei; Wang, Raymond Y.; Ellinwood, N. Matthew; Guzman, Miguel A.; Shapiro, Elsa G.; Dickson, Patricia I.

    2015-01-01

    Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

  15. NATO Enlargement 2000 - 2015. Implications for Defense Planning

    DTIC Science & Technology

    2001-01-01

    alliance, while reaffirming its commitment to the collective defense of its members, expanded its mission to include conflict prevention and conflict ... management throughout Europe, including areas outside the boundaries of the NATO treaty area. Both NATO’s enlargement and its transformation have been

  16. Viewing-zone enlargement method for sampled hologram that uses high-order diffraction.

    PubMed

    Mishina, Tomoyuki; Okui, Makoto; Okano, Fumio

    2002-03-10

    We demonstrate a method of enlarging the viewing zone for holography that has holograms with a pixel structure. First, aliasing generated by the sampling of a hologram by pixel is described. Next the high-order diffracted beams reproduced from the hologram that contains aliasing are explained. Finally, we show that the viewing zone can be enlarged by combining these high-order reconstructed beams from the hologram with aliasing.

  17. Alterations in brain temperatures as a possible cause of migraine headache.

    PubMed

    Horváth, Csilla

    2014-05-01

    Migraine is a debilitating disease with a recurring generally unilateral headache and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that affects some 11-18% of the population. Most of the mechanisms previously put forward to explain the attacks have been questioned or give an explanation only some of the symptoms. Moreover, the best drugs for treatment are still the 20-year-old triptans, which have serious limitations as regards both efficacy and tolerability. As the dura and some cranial vessels are the only intracranial structures capable of pain sensations, a vascular theory of migraine emerged, but has been debated. Recent theories identified the hyperexcitability of structures involved in pain transmission, such as the trigeminal system or the cortex, or an abnormal modulatory function of the brainstem. However, there is ongoing scientific debate concerning these theories, neither of which is fully capable of explaining the occurrence of a migraine attack. The present article puts forward a hypothesis of the possibility of abnormal temperature regulation in certain regions or the overall brain in migraineurs, the attack being a defense mechanism to prevent neuronal damage. Few examinations have been made of temperature regulation in the human brain. It lacks the carotid rete, a vascular heat exchanger that serves in many animals to provide constant brain temperature. The human brain contains a high density of neurons with a considerable energy demand that is converted to heat. The human brain has a higher temperature than other parts of the body and needs continuous cooling. Recent studies revealed unexpectedly great variations in temperature of various structures of the brain and considerable changes in response to functional activation. There is various evidence in support of the hypothesis that accumulated heat in some structure or the overall brain may be behind the symptoms observed, such as a platelet abnormality, a decreased

  18. Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

    PubMed

    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.

  19. Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence.

    PubMed

    Choy, Christopher H; Saffi, Golam; Gray, Matthew A; Wallace, Callen; Dayam, Roya M; Ou, Zhen-Yi A; Lenk, Guy; Puertollano, Rosa; Watkins, Simon C; Botelho, Roberto J

    2018-05-21

    Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects, including embryonic lethality, neurodegeneration and overt inflammation. The reasons for such drastic lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF, enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition, and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells. © 2018. Published by The Company of Biologists Ltd.

  20. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

    PubMed

    Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

    2011-07-07

    Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

  1. mTOR regulates brain morphogenesis by mediating GSK3 signaling

    PubMed Central

    Ka, Minhan; Condorelli, Gianluigi; Woodgett, James R.; Kim, Woo-Yang

    2014-01-01

    Balanced control of neural progenitor maintenance and neuron production is crucial in establishing functional neural circuits during brain development, and abnormalities in this process are implicated in many neurological diseases. However, the regulatory mechanisms of neural progenitor homeostasis remain poorly understood. Here, we show that mammalian target of rapamycin (mTOR) is required for maintaining neural progenitor pools and plays a key role in mediating glycogen synthase kinase 3 (GSK3) signaling during brain development. First, we generated and characterized conditional mutant mice exhibiting deletion of mTOR in neural progenitors and neurons in the developing brain using Nestin-cre and Nex-cre lines, respectively. The elimination of mTOR resulted in abnormal cell cycle progression of neural progenitors in the developing brain and thereby disruption of progenitor self-renewal. Accordingly, production of intermediate progenitors and postmitotic neurons were markedly suppressed. Next, we discovered that GSK3, a master regulator of neural progenitors, interacts with mTOR and controls its activity in cortical progenitors. Finally, we found that inactivation of mTOR activity suppresses the abnormal proliferation of neural progenitors induced by GSK3 deletion. Our findings reveal that the interaction between mTOR and GSK3 signaling plays an essential role in dynamic homeostasis of neural progenitors during brain development. PMID:25273085

  2. Abnormalities of Object Visual Processing in Body Dysmorphic Disorder

    PubMed Central

    Feusner, Jamie D.; Hembacher, Emily; Moller, Hayley; Moody, Teena D.

    2013-01-01

    Background Individuals with body dysmorphic disorder may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with body dysmorphic disorder have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. Methods Fourteen medication-free participants with DSM-IV body dysmorphic disorder and 14 healthy controls participated. We performed functional magnetic resonance imaging while participants matched photographs of houses that were unaltered, contained only high spatial frequency (high detail) information, or only low spatial frequency (low detail) information. The primary outcome was group differences in blood oxygen level-dependent signal changes. Results The body dysmorphic disorder group showed lesser activity in the parahippocampal gyrus, lingual gyrus, and precuneus for low spatial frequency images. There were greater activations in medial prefrontal regions for high spatial frequency images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lesser activity in dorsal occipital cortex and ventrolateral prefrontal cortex for normal and high spatial frequency images. Conclusions Individuals with body dysmorphic disorder have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details is consistent with a model of imbalances in global vs. local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms. PMID:21557897

  3. Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

    PubMed Central

    Mac Donald, Christine L.; Johnson, Ann M.; Cooper, Dana; Nelson, Elliot C.; Werner, Nicole J.; Shimony, Joshua S.; Snyder, Abraham Z.; Raichle, Marcus E.; Witherow, John R.; Fang, Raymond; Flaherty, Stephen F.; Brody, David L.

    2011-01-01

    BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast

  4. Impact of brain injury on functional measures of amplitude-integrated EEG at term equivalent age in premature infants.

    PubMed

    El Ters, N M; Vesoulis, Z A; Liao, S M; Smyser, C D; Mathur, A M

    2017-08-01

    To evaluate the association between qualitative and quantitative amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain injury on magnetic resonance imaging (MRI) in preterm infants. A cohort of premature infants born at <30 weeks of gestation and with moderate-to-severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of gestational age-matched control infants also born at <30 weeks of gestation with none/mild injury on MRI was also recruited. Quantitative aEEG measures, including maximum and minimum amplitudes, bandwidth span and spectral edge frequency (SEF 90 ), were calculated using an offline software package. The aEEG recordings were qualitatively scored using the Burdjalov system. MRI scans, performed on the same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42) weeks and were scored for abnormality in a blinded manner using an established MRI scoring system. Twenty-eight (46.7%) infants had a normal MRI or mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain abnormality. Univariate regression analysis demonstrated an association between severity of brain abnormality and quantitative measures of left and right SEF 90 and bandwidth span (β=-0.38, -0.40 and 0.30, respectively) and qualitative measures of cyclicity, continuity and total Burdjalov score (β=-0.10, -0.14 and -0.12, respectively). After correcting for confounding variables, the relationship between MRI abnormality score and aEEG measures of SEF 90 , bandwidth span and Burdjalov score remained significant. Brain abnormalities on MRI at TEA in premature infants are associated with abnormalities on term aEEG measures, suggesting that anatomical brain injury may contribute to delay in functional brain maturation as assessed using aEEG.

  5. Evaluating the Patterns of Aging-Related Tau Astrogliopathy Unravels Novel Insights Into Brain Aging and Neurodegenerative Diseases.

    PubMed

    Kovacs, Gabor G; Robinson, John L; Xie, Sharon X; Lee, Edward B; Grossman, Murray; Wolk, David A; Irwin, David J; Weintraub, Dan; Kim, Christopher F; Schuck, Theresa; Yousef, Ahmed; Wagner, Stephanie T; Suh, Eunran; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Trojanowski, John Q

    2017-04-01

    The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania. We found that (i) the amygdala is a hotspot for all ARTAG types; (ii) age at death, male sex, and presence of primary frontotemporal lobar degeneration (FTLD) tauopathy are significantly associated with ARTAG; (iii) age at death, greater degree of brain atrophy, ventricular enlargement, and Alzheimer disease (AD)-related variables are associated with subpial, white matter, and perivascular ARTAG types; (iv) AD-related variables are associated particularly with lobar white matter ARTAG; and (v) gray matter ARTAG in primary FTLD-tauopathies appears in areas without neuronal tau pathology. We provide a reference map of ARTAG types and propose at least 5 constellations of ARTAG. Furthermore, we propose a conceptual link between primary FTLD-tauopathy and ARTAG-related astrocytic tau pathologies. Our observations serve as a basis for etiological stratification and definition of progression patterns of ARTAG. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  6. A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

    PubMed

    Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

    2018-01-09

    Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

  7. A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

    PubMed Central

    Shafi, Mouhsin M.; Whitfield-Gabrieli, Susan; Chu, Catherine J.; Pascual-Leone, Alvaro; Chang, Bernard S.

    2017-01-01

    Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be

  8. Harmonious functional and aesthetic correction of severe localised pregnancy-induced gingival enlargement associated with capillary haemangioma

    PubMed Central

    Kaushal, Shalini; Kumar, Avadhesh; Azmatullah, Mohammed; Gupta, Sanjay; Singh, Rajeev Kumar

    2013-01-01

    Gingival enlargement is a clinical condition that has been widely studied and is directly associated with specific local or systemic conditions. Pregnancy has been presented to increase susceptibility to gingival inflammation. Sex hormones are believed to be a risk factor for periodontitis because of their ability to proliferate specific periodontal microorganisms and affect host immunological response, but it is unclear whether pregnancy gingivitis exposes or proceeds to periodontitis. In this case report, the patient reported with severe localised enlarged gingival mass which initiated when she was pregnant. After parturition, gingival enlargement was persisting and causing functional and aesthetic problem. Enlargement did not resolve even after non-surgical therapy; therefore, surgical excision of the entire enlarged gingival mass was preformed. Histopathological examination revealed capillary haemangioma. No evidence of malignancy was seen. No recurrence was seen even after 2 years of follow-up. PMID:23774710

  9. Early white matter abnormalities, progressive brain pathology and motor deficits in a novel knock-in mouse model of Huntington's disease

    PubMed Central

    Jin, Jing; Peng, Qi; Hou, Zhipeng; Jiang, Mali; Wang, Xin; Langseth, Abraham J.; Tao, Michael; Barker, Peter B.; Mori, Susumu; Bergles, Dwight E.; Ross, Christopher A.; Detloff, Peter J.; Zhang, Jiangyang; Duan, Wenzhen

    2015-01-01

    White matter abnormalities have been reported in premanifest Huntington's disease (HD) subjects before overt striatal neuronal loss, but whether the white matter changes represent a necessary step towards further pathology and the underlying mechanism of these changes remains unknown. Here, we characterized a novel knock-in mouse model that expresses mouse HD gene homolog (Hdh) with extended CAG repeat- HdhQ250, which was derived from the selective breeding of HdhQ150 mice. HdhQ250 mice manifest an accelerated and robust phenotype compared with its parent line. HdhQ250 mice exhibit progressive motor deficits, reduction in striatal and cortical volume, accumulation of mutant huntingtin aggregation, decreased levels of DARPP32 and BDNF and altered striatal metabolites. The abnormalities detected in this mouse model are reminiscent of several aspects of human HD. In addition, disturbed myelination was evident in postnatal Day 14 HdhQ250 mouse brain, including reduced levels of myelin regulatory factor and myelin basic protein, and decreased numbers of myelinated axons in the corpus callosum. Thinner myelin sheaths, indicated by increased G-ratio of myelin, were also detected in the corpus callosum of adult HdhQ250 mice. Moreover, proliferation of oligodendrocyte precursor cells is altered by mutant huntingtin both in vitro and in vivo. Our data indicate that this model is suitable for understanding comprehensive pathogenesis of HD in white matter and gray matter as well as developing therapeutics for HD. PMID:25609071

  10. The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder.

    PubMed

    Abramovic, Lucija; Boks, Marco P M; Vreeker, Annabel; Bouter, Diandra C; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H; Ophoff, Roel A; Kahn, René S; van Haren, Neeltje E M

    2016-11-01

    There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  11. Patterns of differences in brain morphology in humans as compared to extant apes.

    PubMed

    Aldridge, Kristina

    2011-01-01

    Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Patterns of differences in brain morphology in humans as compared to extant apes

    PubMed Central

    Aldridge, Kristina

    2010-01-01

    Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. PMID:21056456

  13. Correlation between blink reflex abnormalities and magnetic resonance imaging findings in patients with multiple sclerosis.

    PubMed

    Degirmenci, Eylem; Erdogan, Cagdas; Bir, Levent Sinan

    2013-09-01

    This study investigates the correlation between brain magnetic resonance imaging findings and blink reflex abnormalities in patients with relapsing remitting multiple sclerosis. Twenty-six patients and 17 healthy subjects were included in this study. Blink reflex test (BRT) results were obtained using right and left stimulations; thus, 52 BRT results were recorded for the patient group, and 34 BRT results were recorded for the control group. The magnetic resonance imaging (MRI) findings were classified based on the existence of brainstem lesions (hyperintense lesion on T2 weighted (W) and fast fluid-attenuated inversion recovery MRI or contrast-enhancing lesion on T1W MRI). Correlation analysis was performed for the BRT and MRI findings. The percentage of individuals with abnormal BRT results (including R1 latency, ipsilateral R2 latency, and contralateral R2 latency) was significantly higher in the patient group as compared to the control group (p values: 0.015, 0.001, and 0.002, respectively). Correlation analysis revealed significant correlations between contralateral R2 latency abnormalities and brainstem lesions (p value: 0.011). Our results showed significant correlation correlations between contralateral R2 latency abnormalities and brainstem lesions and these results may be explained the effects of multiple demyelinating lesions of the brain stem of patients with relapsing remitting multiple sclerosis.

  14. Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A Cross-Sectional Study.

    PubMed

    Quiroz, Yakeel T; Schultz, Aaron P; Chen, Kewei; Protas, Hillary D; Brickhouse, Michael; Fleisher, Adam S; Langbaum, Jessica B; Thiyyagura, Pradeep; Fagan, Anne M; Shah, Aarti R; Muniz, Martha; Arboleda-Velasquez, Joseph F; Munoz, Claudia; Garcia, Gloria; Acosta-Baena, Natalia; Giraldo, Margarita; Tirado, Victoria; Ramírez, Dora L; Tariot, Pierre N; Dickerson, Bradford C; Sperling, Reisa A; Lopera, Francisco; Reiman, Eric M

    2015-08-01

    cingulate cortex with medial temporal lobe regions (mean [SD] parameter estimates were 0.038 [0.070] for noncarriers and 0.190 [0.057] for carriers), as well as greater gray matter volumes in temporal regions (eg, left parahippocampus; P < . 049, corrected for multiple comparisons). Children at genetic risk for ADAD have functional and structural brain changes and abnormal levels of plasma Aβ1-42. The extent to which the underlying brain changes are either neurodegenerative or developmental remains to be determined. This study provides additional information about the earliest known biomarker changes associated with ADAD.

  15. Temporal bone changes in patients with Goldenhar syndrome with special emphasis on inner ear abnormalities.

    PubMed

    Hennersdorf, Florian; Friese, Natascha; Löwenheim, Hubert; Tropitzsch, Anke; Ernemann, Ulrike; Bisdas, Sotirios

    2014-06-01

    Goldenhar syndrome is a developmental disorder presenting with orofacial and vertebral anomalies, which are also accompanied by abnormalities in other organs. We examined temporal bone changes with special emphasis on inner ear abnormalities in these patients. A retrospective review of 7 new cases in addition to a previously published series of 14 cases with clinically diagnosed Goldenhar syndrome was carried out to search for inner ear anomalies. In addition, temporal bone imaging studies from the literature were summarized and compared with our results. Departments of Neuroradiology and Otorhinolaryngology at a university hospital. In addition to the previous series of 14 patients, 7 new patients with Goldenhar syndrome were identified. Patients underwent otologic examination, audiometric studies, and high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) of the temporal bone. Temporal bone changes and specifically inner ear malformations. Nineteen of 21 patients showed changes of the external and middle ear correlating with the literature. Seven of 21 patients showed inner ear abnormalities constituting one-third of all patients. These ranged from mild such as vestibular enlargement to severe defects such as cochlear hypoplasia and common cavity. Inner ear abnormalities were present in one-third of patients. Although in some cases, these might not be of clinical significance, some patients show severe defects of the inner ear requiring more complex hearing loss therapy. Therefore, imaging of the temporal bone structures is important in the care of these patients.

  16. Prolactin deficiency, obesity, and enlarged testes--a new syndrome?

    PubMed Central

    Roitman, A; Assa, S; Kauli, R; Laron, Z

    1980-01-01

    A 4-year-old boy is described who was obese and slightly mentally retarded. His testes were enlarged. The only endocrine disorder present was a failure to increase plasma prolactin after stimulation. Images Figure PMID:7436524

  17. Quantitative analysis of brain magnetic resonance imaging for hepatic encephalopathy

    NASA Astrophysics Data System (ADS)

    Syh, Hon-Wei; Chu, Wei-Kom; Ong, Chin-Sing

    1992-06-01

    High intensity lesions around ventricles have recently been observed in T1-weighted brain magnetic resonance images for patients suffering hepatic encephalopathy. The exact etiology that causes magnetic resonance imaging (MRI) gray scale changes has not been totally understood. The objective of our study was to investigate, through quantitative means, (1) the amount of changes to brain white matter due to the disease process, and (2) the extent and distribution of these high intensity lesions, since it is believed that the abnormality may not be entirely limited to the white matter only. Eleven patients with proven haptic encephalopathy and three normal persons without any evidence of liver abnormality constituted our current data base. Trans-axial, sagittal, and coronal brain MRI were obtained on a 1.5 Tesla scanner. All processing was carried out on a microcomputer-based image analysis system in an off-line manner. Histograms were decomposed into regular brain tissues and lesions. Gray scale ranges coded as lesion were then brought back to original images to identify distribution of abnormality. Our results indicated the disease process involved pallidus, mesencephalon, and subthalamic regions.

  18. Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

    PubMed

    Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

    2015-11-01

    The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the

  19. Excision of an enlarging vaginal epidermal inclusion cyst during pregnancy: a case report.

    PubMed

    Pereira, Nigel; Guilfoil, Daniel S

    2012-07-01

    The study aimed to report the case of a patient with an enlarging and symptomatic epidermal inclusion cyst during pregnancy that required surgical excision. This study was a case report of a 28-year-old woman (gravida 8, para 5, aborta 2) at a gestational age of 18 weeks 5 days who reported a tender vaginal mass that had grown larger for more than a week. An enlarging symptomatic cystic mass was surgically excised. Histopathologic findings of the excised mass were consistent with an epidermal inclusion cyst with surrounding moderate chronic inflammation and cyst rupture. The patient's symptoms resolved completely by her postoperative visit. Although most epithelial inclusion cysts are asymptomatic and can be managed expectantly, cysts that enlarge or become symptomatic should be excised surgically.

  20. Enlargement of basilar artery aneurysms following balloon occlusion--"water-hammer effect". Report of two cases.

    PubMed

    Kwan, E S; Heilman, C B; Shucart, W A; Klucznik, R P

    1991-12-01

    Two patients with distal basilar aneurysms were treated with intra-aneurysmal balloon occlusion. After apparently successful therapy, follow-up angiograms demonstrated aneurysm enlargement with balloon migration distally in the sac. Geometric mismatch between the base of the balloons and the aneurysm neck together with transmitted pulsation through the 2-hydroxyl-ethylmethacrylate (HEMA)-filled balloon directly contributed to aneurysm enlargement. In this report, the authors discuss the problems of progressive aneurysm enlargement due to a "water-hammer effect" and the possibility of hemorrhage following subtotal occlusion.

  1. Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

    PubMed Central

    Liu, Yu-Ju; Tsai, Po-Yi; Chern, Yijuang

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS. PMID:28522961

  2. Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder

    PubMed Central

    Piras, I.S.; Haapanen, L.; Napolioni, V.; Sacco, R.; Van de Water, J.; Persico, A.M.

    2014-01-01

    Circulating 45 and 62 kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73 kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N = 355), their unaffected siblings (N = 142) and mothers (N = 333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62 kDa antibodies are correlated with autism severity: the 45 kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62 kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P < 0.05). On the other hand, maternal 37, 39 and 73 kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P < 0.05). Presence of the 62 kDa autoAb in the child is significantly associated with presence of the 39 and/or 73 kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for antibrain antibodies in autism while demonstrating their familial clustering. PMID:24389156

  3. Gingival enlargement in a pregnant woman with acute monocytic leukaemia: a case report.

    PubMed

    Fu, Y-W; Xu, H-Z

    2017-09-01

    The objective of the present study was to report the case of a pregnant woman with severe gingival enlargement for 3 months with undiagnosed acute leukaemia. The pregnant woman presented with anaemia and generalized gingival enlargement. A provisional diagnosis of gingival enlargement in pregnancy was made. Twelve days after the initial treatment, the patient was referred and admitted to the haematology department of a local hospital with clinical signs of anaemia and thrombocytopenia. Blood count showed a white blood cell count of 9.68 × 10 9 /L, with a haemoglobin count of 64.0 g/L and a platelet count of 17 × 10 9 /L. Bone marrow aspiration showed 94.5% monoblasts, and the morphological diagnosis was acute monocytic leukaemia. One day after admission, the patient delivered a male infant by Caesarean section. Ten days after the Caesarean section, the patient was started on a course of chemotherapy. Pulmonary infection, hypokalaemia, and respiratory failure developed, and the patient died 23 days after the Caesarean section. The present case shows the importance of awareness of severe gingival enlargement as an initial oral sign of acute leukaemia. © 2017 Australian Dental Association.

  4. Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases

    PubMed Central

    Wheeler, Richard; Turner, Robert D.; Bailey, Richard G.; Salamaga, Bartłomiej; Mesnage, Stéphane; Mohamad, Sharifah A. S.; Hayhurst, Emma J.; Horsburgh, Malcolm; Hobbs, Jamie K.

    2015-01-01

    ABSTRACT Most bacterial cells are enclosed in a single macromolecule of the cell wall polymer, peptidoglycan, which is required for shape determination and maintenance of viability, while peptidoglycan biosynthesis is an important antibiotic target. It is hypothesized that cellular enlargement requires regional expansion of the cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that are together required for cell enlargement and correct cellular morphology of Staphylococcus aureus, demonstrating the overall importance of this enzyme activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the explanation of the observed morphological defects in terms of the mechanical and biochemical properties of peptidoglycan. It was shown that cells lacking groups of these hydrolases have increased surface stiffness and, in the absence of SagB, substantially increased glycan chain length. This indicates that, beyond their established roles (for example in cell separation), some hydrolases enable cellular enlargement by making peptidoglycan easier to stretch, providing the first direct evidence demonstrating that cellular enlargement occurs via modulation of the mechanical properties of peptidoglycan. PMID:26220963

  5. Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice

    PubMed Central

    Nielsen, Corinne M.; Cuervo, Henar; Ding, Vivianne W.; Kong, Yupeng; Huang, Eric J.; Wang, Rong A.

    2014-01-01

    Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis. PMID:25209249

  6. Enlargement and sculpturing of a small and deformed glans.

    PubMed

    Perovic, Savra; Radojicic, Zoran I; Djordjevic, Miroslav Lj; Vukadinovic, Vojkan V

    2003-10-01

    We present 2 techniques of enhancement and sculpturing of a small and/or deformed glans. The small glans in primary or re-do hypospadias repair was enhanced by longitudinal double-faced island flaps incorporated onto the ventral side of the glans between the glans wings. The deformed glans, of small or normal size (with normal urethra or well functioning neourethra), was enlarged and sculptured by injection of hydrogel. Between May 1997 and March 2002, 27 patients underwent glans enhancement and sculpturing. Small deformed glans occurred after failed hypospadias repair in 10 patients, penile trauma in 3, hemangioma sclerozation in 2, primary hypospadias in 8 and normally developed penile body in 4. A double-faced island flap was performed in 14 patients, glans was enhanced by hydrogel injection in 9 and both procedures were performed in 4. Mean followup was 34 months for the double-faced flap technique 17 months for hydrogel injection. Satisfactory enlargement and esthetic appearance were achieved in 13 of the 14 patients who underwent the double-faced flap technique and 1 required surgical correction. Of the 9 patients who underwent either single or multistage hydrogel injection 8 had good results and 1 required partial removal of hydrogel after hypercorrection. The combination of these 2 techniques provided satisfactory results in all 4 cases. Enlargement and sculpturing of a small deformed glans are challenging and difficult. A double-faced island flap and/or injection of hydrogel resolves this problem satisfactorily.

  7. Amygdala enlargement and emotional responses in (autoimmune) temporal lobe epilepsy.

    PubMed

    Holtmann, Olga; Schlossmacher, Insa; Moenig, Constanze; Johnen, Andreas; Rutter, Lisa-Marie; Tenberge, Jan-Gerd; Schiffler, Patrick; Everding, Judith; Golombeck, Kristin S; Strippel, Christine; Dik, Andre; Schwindt, Wolfram; Wiendl, Heinz; Meuth, Sven G; Bruchmann, Maximilian; Melzer, Nico; Straube, Thomas

    2018-06-22

    Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.

  8. Abnormal activation of the social brain during face perception in autism.

    PubMed

    Hadjikhani, Nouchine; Joseph, Robert M; Snyder, Josh; Tager-Flusberg, Helen

    2007-05-01

    ASD involves a fundamental impairment in processing social-communicative information from faces. Several recent studies have challenged earlier findings that individuals with autism spectrum disorder (ASD) have no activation of the fusiform gyrus (fusiform face area, FFA) when viewing faces. In this study, we examined activation to faces in the broader network of face-processing modules that comprise what is known as the social brain. Using 3T functional resonance imaging, we measured BOLD signal changes in 10 ASD subjects and 7 healthy controls passively viewing nonemotional faces. We replicated our original findings of significant activation of face identity-processing areas (FFA and inferior occipital gyrus, IOG) in ASD. However, in addition, we identified hypoactivation in a more widely distributed network of brain areas involved in face processing [including the right amygdala, inferior frontal cortex (IFC), superior temporal sulcus (STS), and face-related somatosensory and premotor cortex]. In ASD, we found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (IFC, STS) and other face-processing areas. The severity of the social symptoms measured by the Autism Diagnostic Observation Schedule was correlated with the right IFC cortical thickness and with functional activation in that area. When viewing faces, adults with ASD show atypical patterns of activation in regions forming the broader face-processing network and social brain, outside the core FFA and IOG regions. These patterns suggest that areas belonging to the mirror neuron system are involved in the face-processing disturbances in ASD.

  9. Effect analysis of intradermal hyaluronic acid injection to treat enlarged facial pores.

    PubMed

    Qian, Wei; Zhang, Yan-Kun; Hou, Ying; Lyu, Wei; Cao, Qian; Li, Yan-Qi; Fan, Ju-Feng

    2017-08-08

    To investigate the clinical application and efficacy of intradermal injection of low molecular weight hyaluronic acid (LMW-HA) for treating enlarged facial pores. From January 2015 to May 2016, 42 subjects who sought aesthetic treatment underwent intradermal injection of LMW-HA to improve enlarged facial pores. For each treatment, 2.5 mL (25 mg) of LMW-HA was injected into the skin of the full face. The treatment was repeated 2-5 times with an interval of 1 to 1.5 months between consecutive treatments. The postoperative follow-up period was 1 to 6 months. Statistical analysis was used to compare the degree of enlargement of facial pores before and after injection. The clinical efficacy and adverse effects were recorded. The enlarged facial pores before and after treatment were categorized and subjected to the Wilcoxon matched-pairs signed-rank test. The difference was statistically significant (P<.01). The improvement rate was 40.03±18.41%. No infection, nodules, or pigmentation was reported at the injection sites in the subjects who sought aesthetic treatment. The overall satisfaction rate was 92.8%. Intradermal injection of LMW-HA can significantly improve skin texture, reduce pore size, and enhance skin radiance. The injection technique was simple, safe, and effective and could easily be extended to clinical practice. © 2017 Wiley Periodicals, Inc.

  10. Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

    PubMed

    Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

    2016-07-01

    This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment. © The Author(s) 2016.

  11. Addiction Related Alteration in Resting-state Brain Connectivity

    PubMed Central

    Ma, Ning; Liu, Ying; Li, Nan; Wang, Chang-Xin; Zhang, Hao; Jiang, Xiao-Feng; Xu, Hu-Sheng; Fu, Xian-Ming; Hu, Xiaoping; Zhang, Da-Ren

    2009-01-01

    It is widely accepted that addictive drug use is related to abnormal functional organization in the user’s brain. The present study aimed to identify this type of abnormality within the brain networks implicated in addiction by resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI). With fMRI data acquired during resting state from 14 chronic heroin users (12 of whom were being treated with methadone) and 13 non-addicted controls, we investigated the addiction related alteration in functional connectivity between the regions in the circuits implicated in addiction with seed-based correlation analysis. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens and ventral/rostral anterior cingulate cortex (ACC), and orbital frontal cortex (OFC), between amygdala and OFC; and reduced functional connectivity between prefrontal cortex and OFC, and ACC. These observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state. PMID:19703568

  12. High prevalence of brain pathology in violent prisoners: a qualitative CT and MRI scan study.

    PubMed

    Schiltz, Kolja; Witzel, Joachim G; Bausch-Hölterhoff, Josef; Bogerts, Bernhard

    2013-10-01

    The aim of this study was to determine the frequency and extent of brain anomalies in a large sample of incarcerated violent offenders not previously considered neuropsychiatrically ill, in comparison with non-violent offenders and non-offending controls. MRI and CT brain scans from 287 male prison inmates (162 violent and 125 non-violent) not diagnosed as mentally ill before that were obtained due to headache, vertigo or psychological complaints during imprisonment were assessed and compared to 52 non-criminal controls. Brain scans were rated qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1) or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex and medial temporal structures bilaterally as well as third ventricle. Overall, offenders displayed a significantly higher rate of morphological abnormality, with the violent offenders scoring significantly higher than non-violent offenders and controls. This difference was statistically detectable for frontal/parietal cortex, medial temporal structures, third ventricle and the left but not the right lateral ventricle. The remarkable prevalence of brain pathology in convicted violent prisoners detectable by neuroradiological routine assessment not only highlights the importance of frontal and temporal structures in the control of social, and specifically of violent behaviour, but also raises questions on the legal culpability of violent offenders with brain abnormalities. The high proportion of undetected presence of structural brain damage emphasizes the need that in violent criminals, the comprehensive routine neuropsychiatric assessment usually performed in routine forensic psychiatric expertises should be complemented with brain imaging.

  13. Brain magnetic resonance imaging findings in Smith-Lemli-Opitz syndrome.

    PubMed

    Lee, Ryan W Y; Conley, Sandra K; Gropman, Andrea; Porter, Forbes D; Baker, Eva H

    2013-10-01

    Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by inborn errors of cholesterol metabolism resulting from mutations in 7-dehydrocholesterol reductase (DHCR7). There are only a few studies describing the brain imaging findings in SLOS. This study examines the prevalence of magnetic resonance imaging (MRI) abnormalities in the largest cohort of patients with SLOS to date. Fifty-five individuals with SLOS (27 M, 28 F) between age 0.17 years and 25.4 years (mean = 6.2, SD = 5.8) received a total of 173 brain MRI scans (mean = 3.1 per subject) on a 1.5T GE scanner between September 1998 and December 2003, or on a 3T Philips scanner between October 2010 and September 2012; all exams were performed at the Clinical Center of the National Institutes of Health. We performed a retrospective review of these imaging studies for both major and minor brain anomalies. Aberrant MRI findings were observed in 53 of 55 (96%) SLOS patients, with abnormalities of the septum pellucidum the most frequent (42/55, 76%) finding. Abnormalities of the corpus callosum were found in 38 of 55 (69%) patients. Other findings included cerebral atrophy, cerebellar atrophy, colpocephaly, white matter lesions, arachnoid cysts, Dandy-Walker variant, and type I Chiari malformation. Significant correlations were observed when comparing MRI findings with sterol levels and somatic malformations. Individuals with SLOS commonly have anomalies involving the midline and para-midline structures of the brain. Further studies are required to examine the relationship between structural brain abnormalities and neurodevelopmental disability in SLOS. © 2013 The Authors. American Journal of Medical Genetics Part A Published by U.S. Government Work.

  14. Long term follow up of idiopathic gingival enlargement associated with chronic periodontitis: A case report and review.

    PubMed

    Nagarale, Girish P; Ravindra, S; Thakur, Srinath; Setty, Swati

    2013-03-01

    Idiopathic gingival enlargement is a rare condition characterized by massive enlargement of the gingiva. It may be associated with other diseases/conditions characterizing a syndrome, but rarely associated with periodontitis. This case report describes an unusual clinical form of gingival enlargement associated with chronic periodontitis. Clinical examination revealed diffuse gingival enlargement. The lesion was asymptomatic, firm, and pinkish red. Generalized periodontal pockets were observed. Radiographic evaluation revealed generalized severe alveolar bone loss. Histopathological investigations revealed atrophic epithelium with dense fibrocollagenous tissue. Lesions healed successfully following extraction and surgical excision, and no recurrence was observed after 1 year follow-up but recurrence was observed at 3 and 5-years follow-up. Successful treatment of idiopathic gingival enlargement depends on proper identification of etiologic factors and improving esthetics and function through surgical excision of the over growth. However, there may be recurrence.

  15. Amygdala and Hippocampus Enlargement during Adolescence in Autism

    ERIC Educational Resources Information Center

    Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

    2010-01-01

    Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

  16. Prediction of vascular abnormalities on CT angiography in patients with acute headache.

    PubMed

    Alons, Imanda M E; Goudsmit, Ben F J; Jellema, Korné; van Walderveen, Marianne A A; Wermer, Marieke J H; Algra, Ale

    2018-05-09

    Patients with acute headache increasingly undergo CT-angiography (CTA) to evaluate underlying vascular causes. The aim of this study is to determine clinical and non-contrast CT (NCCT) criteria to select patients who might benefit from CTA. We retrospectively included patients with acute headache who presented to the emergency department of an academic medical center and large regional teaching hospital and underwent NCCT and CTA. We identified factors that increased the probability of finding a vascular abnormality on CTA, performed multivariable regression analyses and determined discrimination with the c-statistic. A total of 384 patients underwent NCCT and CTA due to acute headache. NCCT was abnormal in 194 patients. Among these, we found abnormalities in 116 cases of which 99 aneurysms. In the remaining 190 with normal NCCT we found abnormalities in 12 cases; four unruptured aneurysms, three cerebral venous thrombosis', two reversible cerebral vasoconstriction syndromes, two cervical arterial dissections and one cerebellar infarction. In multivariable analysis abnormal NCCT, lowered consciousness and presentation within 6 hr of headache onset were independently associated with abnormal CTA. The c-statistic of abnormal NCCT alone was 0.80 (95% CI: 0.75-0.80), that also including the other two variables was 0.84 (95% CI: 0.80-0.88). If NCCT was normal no other factors could help identify patients at risk for abnormalities. In patients with acute headache abnormal NCCT is the strongest predictor of a vascular abnormality on CTA. If NCCT is normal no other predictors increase the probability of finding an abnormality on CTA and diagnostic yield is low. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  17. Nature of the abnormal band gap narrowing in highly crystalline Zn1-xCoxO nanorods

    NASA Astrophysics Data System (ADS)

    Qiu, Xiaoqing; Li, Liping; Li, Guangshe

    2006-03-01

    Highly crystalline Zn1-xCoxO nanorods were prepared using a hydrothermal method. With increasing Co2+ dopant concentration, the lattice volume enlarged considerably, which is associated with the enhanced repulsive interactions of defect dipole moments on the wall surfaces. This lattice modification produced a significant decrease in band gap energies with its magnitude that followed the relationship, ΔEg=ΔE0•(e-x/B-1), where x and B are Co2+ dopant concentration and a constant, respectively. The abnormal band gap energies were indicated to originate from the sp-d exchange interactions that are proportional to the square of lattice volume.

  18. Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.

    PubMed

    Hara, Yusuke; Sudo, Tatsuya; Togane, Yu; Akagawa, Hiromi; Tsujimura, Hidenobu

    2018-04-01

    Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers

  19. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    PubMed Central

    2011-01-01

    Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

  20. Microstructure abnormalities in adolescents with internet addiction disorder.

    PubMed

    Yuan, Kai; Qin, Wei; Wang, Guihong; Zeng, Fang; Zhao, Liyan; Yang, Xuejuan; Liu, Peng; Liu, Jixin; Sun, Jinbo; von Deneen, Karen M; Gong, Qiyong; Liu, Yijun; Tian, Jie

    2011-01-01

    Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction. We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD. Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD.