Cerebellar Functional Connectivity in Term‐ and Very Preterm‐Born Infants

&NA; Cortical resting state networks have been consistently identified in infants using resting state‐functional connectivity magnetic resonance imaging (rs‐fMRI). Comparable studies in adults have demonstrated cerebellar components of well‐established cerebral networks. However, there has been limited investigation of early cerebellar functional connectivity. We acquired non‐sedated rs‐fMRI data in the first week of life in 57 healthy, term‐born infants and at term‐equivalent postmenstrual age in 20 very preterm infants (mean birth gestational age 27 ± 2 weeks) without significant cerebral or cerebellar injury. Seed correlation analyses were performed using regions of interests spanning the cortical and subcortical gray matter and cerebellum. Parallel analyses were performed using rs‐fMRI data acquired in 100 healthy adults. Our results demonstrate that cortico‐cerebellar functional connectivity is well‐established by term. Intra‐ and cortico‐cerebellar functional connectivity were largely similar in infants and adults. However, infants showed more functional connectivity structure within the cerebellum, including stronger homotopic correlations and more robust anterior‐posterior anticorrelations. Prematurity was associated with reduced correlation magnitudes, but no alterations in intra‐ and cortico‐cerebellar functional connectivity topography. These results add to the growing evidence that the cerebellum plays an important role in shaping early brain development during infancy.

[1]  Catherine J. Stoodley.  The Cerebellum and Neurodevelopmental Disorders , 2015, The Cerebellum.

[2]  J. Gilmore,et al.  Infant Brain Atlases from Neonates to 1- and 2-Year-Olds , 2011, PloS one.

[3]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[4]  R. Buckner.  The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging , 2013, Neuron.

[5]  Jeremy D. Schmahmann,et al.  Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies , 2009, NeuroImage.

[6]  Catherine J. Stoodley,et al.  The Cerebellum and Cognition: Evidence from Functional Imaging Studies , 2011, The Cerebellum.

[7]  Katherine E. Prater,et al.  Distinct Cerebellar Contributions to Intrinsic Connectivity Networks , 2009, NeuroImage.

[8]  Christopher L. Asplund,et al.  The organization of the human cerebellum estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[9]  A. Gunn,et al.  What brakes the preterm brain? An arresting story , 2014, Pediatric Research.

[10]  H. Glass,et al.  Outcomes for Extremely Premature Infants , 2015, Anesthesia and analgesia.

[11]  Nicolas Guizard,et al.  Injury to the premature cerebellum: outcome is related to remote cortical development. , 2014, Cerebral cortex.

[12]  J. Stein,et al.  Cerebellar Function in Developmental Dyslexia , 2012, The Cerebellum.

[13]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[14]  Catherine Limperopoulos,et al.  Does Cerebellar Injury in Premature Infants Contribute to the High Prevalence of Long-term Cognitive, Learning, and Behavioral Disability in Survivors? , 2007, Pediatrics.

[15]  Nicolas Guizard,et al.  Regional Cerebellar Volumes Predict Functional Outcome in Children with Cerebellar Malformations , 2011, The Cerebellum.

[16]  M. Steinlin.  The cerebellum in cognitive processes: Supporting studies in children , 2008, The Cerebellum.

[17]  Catherine Limperopoulos,et al.  Structure-function relationships in the developing cerebellum: Evidence from early-life cerebellar injury and neurodevelopmental disorders. , 2016, Seminars in fetal & neonatal medicine.

[18]  M. Steinlin.  Cerebellar Disorders in Childhood: Cognitive Problems , 2008, The Cerebellum.

[19]  F. Turkheimer,et al.  Emergence of resting state networks in the preterm human brain , 2010, Proceedings of the National Academy of Sciences.

[20]  Kevin Murphy,et al.  Towards a consensus regarding global signal regression for resting state functional connectivity MRI , 2017, NeuroImage.

[21]  Masao Ito.  Control of mental activities by internal models in the cerebellum , 2008, Nature Reviews Neuroscience.

[22]  Ninon Burgos,et al.  New advances in the Clinica software platform for clinical neuroimaging studies , 2019 .

[23]  Nicolas Guizard,et al.  Cerebellar Injury in the Premature Infant Is Associated With Impaired Growth of Specific Cerebral Regions , 2010, Pediatric Research.

[24]  T. Huisman,et al.  Prenatal Cerebellar Disruptions: Neuroimaging Spectrum of Findings in Correlation with Likely Mechanisms and Etiologies of Injury. , 2016, Neuroimaging clinics of North America.

[25]  Ralph-Axel Müller,et al.  Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder , 2015, Biological Psychiatry.

[26]  Richard J. T. Wingate,et al.  Consensus Paper: Cerebellar Development , 2015, The Cerebellum.

[27]  Jeffrey J. Neil,et al.  Transport, monitoring, and successful brain MR imaging in unsedated neonates , 2008, Pediatric Radiology.

[28]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Anqi Qiu,et al.  Cerebellar Functional Parcellation Using Sparse Dictionary Learning Clustering , 2016, Front. Neurosci..

[30]  Mark W. Woolrich,et al.  FSL , 2012, NeuroImage.

[31]  J. Volpe.  Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important , 2009, Journal of child neurology.

[32]  S. Foster-Cohen,et al.  Very preterm children show impairments across multiple neurodevelopmental domains by age 4 years , 2009, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[33]  R L Sidman,et al.  Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans , 1970, The Journal of comparative neurology.

[34]  Vijay A. Mittal,et al.  Differential motor and prefrontal cerebello-cortical network development: Evidence from multimodal neuroimaging , 2016, NeuroImage.

[35]  Peter Fransson,et al.  Resting-state networks in the infant brain , 2007, Proceedings of the National Academy of Sciences.

[36]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[37]  M. Onis.  WHO Motor Development Study: Windows of achievement for six gross motor development milestones , 2006, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[38]  J K Smith,et al.  Functional Connectivity MR Imaging Reveals Cortical Functional Connectivity in the Developing Brain , 2008, American Journal of Neuroradiology.

[39]  Jeffrey J Neil,et al.  Use of resting-state functional MRI to study brain development and injury in neonates. , 2015, Seminars in perinatology.

[40]  Anish Mitra,et al.  Resting-State Network Complexity and Magnitude Are Reduced in Prematurely Born Infants. , 2016, Cerebral cortex.

[41]  D. Prayer,et al.  Disrupted cerebellar development in preterm infants is associated with impaired neurodevelopmental outcome , 2008, European Journal of Pediatrics.

[42]  M. Fox,et al.  The global signal and observed anticorrelated resting state brain networks. , 2009, Journal of neurophysiology.

[43]  Dost Öngür,et al.  Anticorrelations in resting state networks without global signal regression , 2012, NeuroImage.

[44]  Abraham Z. Snyder,et al.  Functional connectivity MRI in infants: Exploration of the functional organization of the developing brain , 2011, NeuroImage.

[45]  Jie Lu,et al.  Focal Pontine Lesions Provide Evidence That Intrinsic Functional Connectivity Reflects Polysynaptic Anatomical Pathways , 2011, The Journal of Neuroscience.

[46]  H. Johansen-Berg,et al.  Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. , 2010, Cerebral cortex.

[47]  Tomoki Arichi,et al.  Specialization and integration of functional thalamocortical connectivity in the human infant , 2015, Proceedings of the National Academy of Sciences.

[48]  J. Neil,et al.  New MR Imaging Assessment Tool to Define Brain Abnormalities in Very Preterm Infants at Term , 2013, American Journal of Neuroradiology.

[49]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[50]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[51]  J. Morris,et al.  Loss of Intranetwork and Internetwork Resting State Functional Connections with Alzheimer's Disease Progression , 2012, The Journal of Neuroscience.

[52]  Carl D. Hacker,et al.  Resting state network estimation in individual subjects , 2013, NeuroImage.

[53]  Susanne M. Jaeggi,et al.  Resting state cortico-cerebellar functional connectivity networks: a comparison of anatomical and self-organizing map approaches , 2012, Front. Neuroanat..

[54]  P. P. Berg,et al.  Neurologic and Developmental Disability at Six Years of Age After Extremely Preterm Birth , 2006 .

[55]  Roderick I. Nicolson,et al.  Dyslexia, dysgraphia, procedural learning and the cerebellum , 2011, Cortex.

[56]  Alan C. Evans,et al.  Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. , 2002, JAMA.

[57]  A. Snyder,et al.  Longitudinal analysis of neural network development in preterm infants. , 2010, Cerebral cortex.

[58]  Catherine Limperopoulos,et al.  Functional properties of resting state networks in healthy full-term newborns , 2015, Scientific Reports.

[59]  Aleksandra Badura,et al.  The Cerebellum, Sensitive Periods, and Autism , 2014, Neuron.

[60]  Jack L. Lancaster,et al.  A modality‐independent approach to spatial normalization of tomographic images of the human brain , 1995 .

[61]  Chiara Nosarti,et al.  Vermis and lateral lobes of the cerebellum in adolescents born very preterm , 2005, Neuroreport.

[62]  Catherine Limperopoulos,et al.  Developmental Cerebellar Cognitive Affective Syndrome in Ex-preterm Survivors Following Cerebellar Injury , 2014, The Cerebellum.

[63]  Nasser Kehtarnavaz,et al.  Average field map image template for Echo-Planar image analysis , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[64]  Richard L Robertson,et al.  Late Gestation Cerebellar Growth Is Rapid and Impeded by Premature Birth , 2005, Pediatrics.

[65]  Richard L Robertson,et al.  Impaired Trophic Interactions Between the Cerebellum and the Cerebrum Among Preterm Infants , 2005, Pediatrics.