Long-Term Functional Outcomes and Correlation with Regional Brain Connectivity by MRI Diffusion Tractography Metrics in a Near-Term Rabbit Model of Intrauterine Growth Restriction

Background Intrauterine growth restriction (IUGR) affects 5–10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. Methodology At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. Principal Findings The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. Conclusions The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR. The description of the pattern of microstructural changes underlying functional defects may help to develop biomarkers based in diffusion MRI and connectivity analysis.

[1]  NervousSystem Disorders,et al.  INSTITUTE OF MEDICINE FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS , 2013 .

[2]  Lingzhong Fan,et al.  Inferior frontal white matter asymmetry correlates with executive control of attention , 2013, Human brain mapping.

[3]  E. Gratacós,et al.  Fetal Brain MRI Texture Analysis Identifies Different Microstructural Patterns in Adequate and Small for Gestational Age Fetuses at Term , 2013, Fetal Diagnosis and Therapy.

[4]  S. Khushu,et al.  Individual differences in trait anxiety are associated with white matter tract integrity in fornix and uncinate fasciculus: Preliminary evidence from a DTI based tractography study , 2013, Behavioural Brain Research.

[5]  F. Scott Hall,et al.  Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene–environment interactions? , 2012, Physiology & Behavior.

[6]  J. Fadel,et al.  Comparison of the activation of somatostatin- and neuropeptide Y-containing neuronal populations of the rat amygdala following two different anxiogenic stressors , 2012, Experimental Neurology.

[7]  Karim Nader,et al.  Involvement of the anterior cingulate cortex in formation, consolidation, and reconsolidation of recent and remote contextual fear memory. , 2012, Learning & memory.

[8]  Do P. M. Tromp,et al.  Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. , 2012, Archives of general psychiatry.

[9]  Sarah Durston,et al.  Decreased frontostriatal microstructural organization in attention deficit/hyperactivity disorder , 2012, Human brain mapping.

[10]  V. Mathews,et al.  White matter abnormalities associated with disruptive behavior disorder in adolescents with and without attention-deficit/hyperactivity disorder , 2012, Psychiatry Research: Neuroimaging.

[11]  M. Barbe,et al.  Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage , 2012, Behavioural Brain Research.

[12]  W. Chang,et al.  Comparing quantitative tractography metrics of motor and sensory pathways in children with periventricular leukomalacia and different levels of gross motor function , 2012, Neuroradiology.

[13]  A. Reiss,et al.  Diffusion tensor imaging reveals white matter abnormalities in Attention-Deficit/Hyperactivity Disorder , 2012, Psychiatry Research: Neuroimaging.

[14]  M. Catani,et al.  Frontotemporal white-matter microstructural abnormalities in adolescents with conduct disorder: a diffusion tensor imaging study , 2012, Psychological Medicine.

[15]  Leire Zubiaurre Elorza,et al.  Tractography of the corticospinal tracts in infants with focal perinatal injury: comparison with normal controls and to motor development , 2012, Neuroradiology.

[16]  David C Rowland,et al.  Neural Correlates of Long-Term Object Memory in the Mouse Anterior Cingulate Cortex , 2012, The Journal of Neuroscience.

[17]  Emma Muñoz-Moreno,et al.  Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome , 2012, NeuroImage.

[18]  Bruce S. McEwen,et al.  Basal anxiety-like behavior predicts differences in dendritic morphology in the medial prefrontal cortex in two strains of rats , 2012, Behavioural Brain Research.

[19]  A. Saykin,et al.  Selective changes in white matter integrity in MCI and older adults with cognitive complaints. , 2012, Biochimica et biophysica acta.

[20]  Emma Muñoz-Moreno,et al.  Neonatal Neurobehavior and Diffusion MRI Changes in Brain Reorganization Due to Intrauterine Growth Restriction in a Rabbit Model , 2012, PloS one.

[21]  R. Halari,et al.  A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention , 2012, Cortex.

[22]  S. Funahashi,et al.  Thalamic mediodorsal nucleus and working memory , 2012, Neuroscience & Biobehavioral Reviews.

[23]  C. Verney,et al.  Neuroanatomical, Sensorimotor and Cognitive Deficits in Adult Rats with White Matter Injury Following Prenatal Ischemia , 2012, Brain pathology.

[24]  L. Lagae,et al.  Integrity of the inferior longitudinal fasciculus and impaired object recognition in children: a diffusion tensor imaging study , 2012, Developmental medicine and child neurology.

[25]  J. Lahti,et al.  Neurocognitive abilities in young adults with very low birth weight , 2011, Neurology.

[26]  J. Kim,et al.  Hippocampal and Prefrontal Projections to the Basal Amygdala Mediate Contextual Regulation of Fear after Extinction , 2011, The Journal of Neuroscience.

[27]  Mary Tolcos,et al.  Intrauterine growth restriction affects the maturation of myelin , 2011, Experimental Neurology.

[28]  Sandra Rees,et al.  The biological basis of injury and neuroprotection in the fetal and neonatal brain , 2011, International Journal of Developmental Neuroscience.

[29]  F. Cauda,et al.  Different functions in the cingulate cortex, a meta-analytic connectivity modeling study , 2011, NeuroImage.

[30]  John D Medaglia,et al.  Examining working memory task acquisition in a disrupted neural network. , 2011, Brain : a journal of neurology.

[31]  Gisella Vetere,et al.  Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory , 2011, Proceedings of the National Academy of Sciences.

[32]  F. Figueras,et al.  Impact on fetal mortality and cardiovascular Doppler of selective ligature of uteroplacental vessels compared with undernutrition in a rabbit model of intrauterine growth restriction. , 2011, Placenta.

[33]  K. Maršál,et al.  Cognitive Function After Intrauterine Growth Restriction and Very Preterm Birth , 2011, Pediatrics.

[34]  Stephen M. Smith,et al.  DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease , 2011, NeuroImage.

[35]  Ralph-Axel Müller,et al.  Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder. , 2011, Journal of child psychology and psychiatry, and allied disciplines.

[36]  R. Geva,et al.  Intrauterine growth-restricted neonates born at term or preterm: how different? , 2011, Pediatric neurology.

[37]  C. Studholme,et al.  Diffusion-Weighted Imaging in Fetuses with Severe Congenital Heart Defects , 2011, American Journal of Neuroradiology.

[38]  E. Gratacós,et al.  Delayed Childbearing: Effects on Fertility and the Outcome of Pregnancy , 2011, Fetal Diagnosis and Therapy.

[39]  A. Ennaceur.  One-trial object recognition in rats and mice: Methodological and theoretical issues , 2010, Behavioural Brain Research.

[40]  Dieter Wolke,et al.  Behavioural symptoms of attention deficit/hyperactivity disorder in preterm and term children born small and appropriate for gestational age: A longitudinal study , 2010, BMC pediatrics.

[41]  Malcolm W. Brown,et al.  Recognition memory: Material, processes, and substrates , 2010, Hippocampus.

[42]  S. Buka,et al.  Fetal growth and the lifetime risk of generalized anxiety disorder , 2010, Depression and anxiety.

[43]  O. Sporns,et al.  White matter maturation reshapes structural connectivity in the late developing human brain , 2010, Proceedings of the National Academy of Sciences.

[44]  Klaus Scheffler,et al.  Structural and functional imaging approaches in attention deficit/hyperactivity disorder: Does the temporal lobe play a key role? , 2010, Psychiatry Research: Neuroimaging.

[45]  N. Bargalló,et al.  Abnormal brain microstructure and metabolism in small‐for‐gestational‐age term fetuses with normal umbilical artery Doppler , 2010, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[46]  F. Crispi,et al.  An Experimental Model of Fetal Growth Restriction Based on Selective Ligature of Uteroplacental Vessels in the Pregnant Rabbit , 2009, Fetal Diagnosis and Therapy.

[47]  Francesc Figueras,et al.  Neurobehavior in Term, Small-for-Gestational Age Infants With Normal Placental Function , 2009, Pediatrics.

[48]  L. Ment,et al.  Imaging biomarkers of outcome in the developing preterm brain , 2009, The Lancet Neurology.

[49]  P. Khong,et al.  Mild Hypoxic-Ischemic Injury in the Neonatal Rat Brain: Longitudinal Evaluation of White Matter Using Diffusion Tensor MR Imaging , 2009, American Journal of Neuroradiology.

[50]  M. Moseley,et al.  Changes in Parahippocampal White Matter Integrity in Amnestic Mild Cognitive Impairment: A Diffusion Tensor Imaging Study , 2009, Behavioural neurology.

[51]  Gail M. Williams,et al.  Fetal growth and behaviour problems in early adolescence: findings from the Mater University Study of Pregnancy. , 2009, International journal of epidemiology.

[52]  P. Whalen,et al.  The Structural Integrity of an Amygdala–Prefrontal Pathway Predicts Trait Anxiety , 2009, The Journal of Neuroscience.

[53]  J. Oosterlaan,et al.  Meta-Analysis of Neurobehavioral Outcomes in Very Preterm and/or Very Low Birth Weight Children , 2009, Pediatrics.

[54]  Jan Sijbers,et al.  Comparing isotropic and anisotropic smoothing for voxel‐based DTI analyses: A simulation study , 2009, Human brain mapping.

[55]  David C Rowland,et al.  Neural correlates of novel object and novel location recognition behavior in the mouse anterior cingulate cortex. , 2009, Journal of neurophysiology.

[56]  J. Grafman,et al.  Neural correlates of anxiety in healthy volunteers: a voxel-based morphometry study. , 2009, The Journal of neuropsychiatry and clinical neurosciences.

[57]  H. Poissant,et al.  [Structural and functional neuroanatomy of attention-deficit hyperactivity disorder (ADHD)]. , 2009, L'Encephale.

[58]  Marcos Martín-Fernández,et al.  Characterization of the similarity between diffusion tensors for image registration , 2009, Comput. Biol. Medicine.

[59]  S. Haber,et al.  The cortico-basal ganglia integrative network: The role of the thalamus , 2009, Brain Research Bulletin.

[60]  Moo K. Chung,et al.  A study of diffusion tensor imaging by tissue-specific, smoothing-compensated voxel-based analysis , 2009, NeuroImage.

[61]  M. VanElzakker,et al.  Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex. , 2008, Learning & memory.

[62]  H. Poissant,et al.  Structural and functional neuroanatomy in attention deficit and hyperactivity disorder (ADHD) , 2008, International Journal of Developmental Neuroscience.

[63]  F. Lazeyras,et al.  Primary cortical folding in the human newborn: an early marker of later functional development. , 2008, Brain : a journal of neurology.

[64]  Simon K Warfield,et al.  Intrauterine Growth Restriction Affects the Preterm Infant's Hippocampus , 2008, Pediatric Research.

[65]  Aina Puce,et al.  The left amygdala knows fear: laterality in the amygdala response to fearful eyes. , 2008, Social cognitive and affective neuroscience.

[66]  Sandra Rees,et al.  An adverse intrauterine environment: implications for injury and altered development of the brain , 2008, International Journal of Developmental Neuroscience.

[67]  E. Melhem,et al.  Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. , 2007, Radiology.

[68]  Stephan E Maier,et al.  Developmental changes and injury induced disruption of the radial organization of the cortex in the immature rat brain revealed by in vivo diffusion tensor MRI. , 2007, Cerebral cortex.

[69]  Pat Levitt,et al.  Three-Dimensional High-Resolution Diffusion Tensor Imaging and Tractography of the Developing Rabbit Brain , 2007, Developmental Neuroscience.

[70]  R. Deriche,et al.  Regularized, fast, and robust analytical Q‐ball imaging , 2007, Magnetic resonance in medicine.

[71]  H. Eichenbaum,et al.  The medial temporal lobe and recognition memory. , 2007, Annual review of neuroscience.

[72]  S. Jang,et al.  Diffusion tensor imaging demonstrates focal lesions of the corticospinal tract in hemiparetic patients with cerebral palsy , 2007, Neuroscience Letters.

[73]  Jean-Marie Bonny,et al.  In vivo analysis of the post‐natal development of normal mouse brain by DTI , 2007, NMR in biomedicine.

[74]  K. Maršál,et al.  Cognitive function in young adults following intrauterine growth restriction with abnormal fetal aortic blood flow , 2007, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[75]  Ariel J. Jaffa,et al.  Neurodevelopmental Outcome of Children With Intrauterine Growth Retardation: A Longitudinal, 10-Year Prospective Study , 2007, Journal of child neurology.

[76]  B. Merker.  Consciousness without a cerebral cortex: A challenge for neuroscience and medicine , 2007, Behavioral and Brain Sciences.

[77]  C. Westin,et al.  Sequential anisotropic Wiener filtering applied to 3D MRI data. , 2007, Magnetic resonance imaging.

[78]  Alexander Drobyshevsky,et al.  A Model of Cerebral Palsy From Fetal Hypoxia-Ischemia , 2007, Stroke.

[79]  Christian Beaulieu,et al.  Voxel based versus region of interest analysis in diffusion tensor imaging of neurodevelopment , 2007, NeuroImage.

[80]  J. P. Huston,et al.  The case for episodic memory in animals , 2006, Neuroscience & Biobehavioral Reviews.

[81]  R. Geva,et al.  Memory functions of children born with asymmetric intrauterine growth restriction , 2006, Brain Research.

[82]  Ruth Feldman,et al.  Neonatal State Organization, Neuromaturation, Mother-Infant Interaction, and Cognitive Development in Small-for-Gestational-Age Premature Infants , 2006, Pediatrics.

[83]  B. Pouzet,et al.  Beneficial effects of galantamine on performance in the object recognition task in Swiss mice: Deficits induced by scopolamine and by prolonging the retention interval , 2006, Pharmacology Biochemistry and Behavior.

[84]  R. Geva,et al.  Neuropsychological Outcome of Children With Intrauterine Growth Restriction: A 9-Year Prospective Study , 2006, Pediatrics.

[85]  Nicholas Ayache,et al.  Clinical DT-MRI estimation, smoothing and fiber tracking with Log-Euclidean metrics , 2006, 3rd IEEE International Symposium on Biomedical Imaging: Nano to Macro, 2006..

[86]  Zhiyi Zuo,et al.  Prenatal hypoxia-induced adaptation and neuroprotection that is inducible nitric oxide synthase-dependent , 2005, Neurobiology of Disease.

[87]  G. Molenaers,et al.  Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury. , 2005, Brain : a journal of neurology.

[88]  Hsiao-Fang Liang,et al.  Formalin fixation alters water diffusion coefficient magnitude but not anisotropy in infarcted brain , 2005, Magnetic resonance in medicine.

[89]  S. Robinson,et al.  Developmental changes induced by graded prenatal systemic hypoxic–ischemic insults in rats , 2005, Neurobiology of Disease.

[90]  A. Tamas,et al.  Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic–ischemic injury , 2005, Behavioural Brain Research.

[91]  Simon K Warfield,et al.  Early Alteration of Structural and Functional Brain Development in Premature Infants Born with Intrauterine Growth Restriction , 2004, Pediatric Research.

[92]  John S. Duncan,et al.  Noninvasive in vivo demonstration of the connections of the human parahippocampal gyrus , 2004, NeuroImage.

[93]  J. Rawlins,et al.  Regional dissociations within the hippocampus—memory and anxiety , 2004, Neuroscience & Biobehavioral Reviews.

[94]  Sheng-Kwei Song,et al.  Relative indices of water diffusion anisotropy are equivalent in live and formalin‐fixed mouse brains , 2003, Magnetic resonance in medicine.

[95]  Gail M Williams,et al.  Learning, cognitive, and attentional problems in adolescents born small for gestational age. , 2003, Pediatrics.

[96]  T. Tsumoto,et al.  Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[97]  Y. Gahéry,et al.  Behavioural changes induced by early and long-term gravito-inertial force modification in the rat , 2003, Behavioural Brain Research.

[98]  P. Hüppi,et al.  Diffusion tensor imaging of normal and injured developing human brain ‐ a technical review , 2002, NMR in biomedicine.

[99]  Carl-Fredrik Westin,et al.  Processing and visualization for diffusion tensor MRI , 2002, Medical Image Anal..

[100]  J. Rawlins,et al.  Hippocampal cytotoxic lesion effects on species-typical behaviours in mice , 2002, Behavioural Brain Research.

[101]  M. Witter,et al.  Projections from the parahippocampal region to the prefrontal cortex in the rat: evidence of multiple pathways , 2002, The European journal of neuroscience.

[102]  D. Mumby.  Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats , 2001, Behavioural Brain Research.

[103]  J. M. Ree,et al.  Adaptation and habituation to an open field and responses to various stressful events in animals with neonatal lesions in the amygdala or ventral hippocampus , 2001, Brain Research.

[104]  James C. Gee,et al.  Spatial transformations of diffusion tensor magnetic resonance images , 2001, IEEE Transactions on Medical Imaging.

[105]  P. Czernichow,et al.  School difficulties in 20-year-olds who were born small for gestational age at term in a regional cohort study. , 2001, Pediatrics.

[106]  Alan C. Evans,et al.  Maturation of white matter in the human brain: a review of magnetic resonance studies , 2001, Brain Research Bulletin.

[107]  Naam Kariv,et al.  Experimental intrauterine growth retardation alters renal development , 2000, Pediatric Nephrology.

[108]  W J Moorman,et al.  Male adolescent exposure to endocrine‐disrupting pesticides: vinclozolin exposure in peripubertal rabbits , 2000, Andrologia.

[109]  J. Kok,et al.  The discrepancy between maturation of visual-evoked potentials and cognitive outcome at five years in very preterm infants with and without hemodynamic signs of fetal brain-sparing. , 2000, Pediatrics.

[110]  P. Toft,et al.  Prenatal and perinatal striatal injury: a hypothetical cause of attention-deficit-hyperactivity disorder? , 1999, Pediatric neurology.

[111]  N. Cowan,et al.  The role of attention in the development of short-term memory: age differences in the verbal span of apprehension. , 1999, Child development.

[112]  J. Aggleton,et al.  The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat , 1997, Behavioural Brain Research.

[113]  H G Vaughan,et al.  Cognitive and neurologic development of the premature, small for gestational age infant through age 6: comparison by birth weight and gestational age. , 1996, Pediatrics.

[114]  George R. Breese,et al.  Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety , 1996, Brain Research.

[115]  D. Treit,et al.  Anxiogenic stimuli in the elevated plus-maze , 1993, Pharmacology Biochemistry and Behavior.

[116]  P. Royston.  A pocket-calculator algorithm for the Shapiro-Francia test for non-normality: an application to medicine. , 1993, Statistics in medicine.

[117]  A. Ennaceur,et al.  A new one-trial test for neurobiological studies of memory in rats. III. Spatial vs. non-spatial working memory , 1992, Behavioural Brain Research.

[118]  H. Eichenbaum,et al.  Complementary roles of the orbital prefrontal cortex and the perirhinal-entorhinal cortices in an odor-guided delayed-nonmatching-to-sample task , 1992 .

[119]  B. Spruijt,et al.  Ethology and neurobiology of grooming behavior. , 1992, Physiological reviews.

[120]  L. Squire.  Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. , 1992, Psychological review.

[121]  L. Squire,et al.  The primate hippocampal formation: evidence for a time-limited role in memory storage. , 1990, Science.

[122]  J. Delacour,et al.  A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data , 1988, Behavioural Brain Research.

[123]  R. Walsh,et al.  Mechanisms mediating the production of environmentally induced brain changes. , 1975, Psychological bulletin.

[124]  J. W. Papez.  A PROPOSED MECHANISM OF EMOTION , 1937 .

[125]  A. Trocino,et al.  Suitability of behavioural tests for determining the ways rabbits function in the environment and their relationship with some productive traits. , 2008 .

[126]  Nicolas Toussaint,et al.  MedINRIA: Medical Image Navigation and Research Tool by INRIA , 2007 .

[127]  L. Gottwald,et al.  [Intrauterine growth restriction]. , 2005, Przeglad lekarski.

[128]  D. Olton,et al.  Hippocampal function required for nonspatial working memory , 2004, Experimental Brain Research.

[129]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[130]  J. W. Papez.  A proposed mechanism of emotion. 1937. , 1995, The Journal of neuropsychiatry and clinical neurosciences.

[131]  Papez Jw.  A proposed mechanism of emotion. 1937. , 1995 .

[132]  G F Koob,et al.  The role of corticotropin-releasing factor in behavioural responses to stress. , 1993, Ciba Foundation symposium.

[133]  H. Eichenbaum,et al.  Complementary roles of the orbital prefrontal cortex and the perirhinal-entorhinal cortices in an odor-guided delayed-nonmatching-to-sample task. , 1992, Behavioral neuroscience.

[134]  C. Pennartz,et al.  Source (or Part of the following Source): Type Article Title the Construction of Semantic Memory: Grammar-based Representations Learned from Relational Episodic Information. Author(s) , 2022 .