Altered brain connectivity in sagittal craniosynostosis

Laboratory investigation

Joel S. Beckett M.D., M.H.S.1, Eric D. Brooks B.S.2, Cheryl Lacadie B.S.3, Brent Vander Wyk Ph.D.4, Roger J. Jou M.D., Ph.D.4, Derek M. Steinbacher D.M.D., M.D.2, R. Todd Constable Ph.D.3,5,6, Kevin A. Pelphrey Ph.D.4, and John A. Persing M.D.2
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  • 1 Department of Neurosurgery, University of California, Los Angeles, California;
  • | 2 Section of Plastic and Reconstructive Surgery, Yale School of Medicine;
  • | 3 Department of Diagnostic Radiology, Yale School of Medicine;
  • | 4 Center for Translational Developmental Neuroscience, Child Study Center, Yale University;
  • | 5 Department of Biomedical Engineering, Yale University; and
  • | 6 Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut
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Object

Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of NSC. The condition is associated with a high prevalence (> 50%) of deficits in executive function. The authors employed diffusion tensor imaging (DTI) and functional MRI to evaluate whether hypothesized structural and functional connectivity differences underlie the observed neurocognitive morbidity of sNSC.

Methods

Using a 3-T Siemens Trio MRI system, the authors collected DTI and resting-state functional connectivity MRI data in 8 adolescent patients (mean age 12.3 years) with sNSC that had been previously corrected via total vault cranioplasty and 8 control children (mean age 12.3 years) without craniosynostosis. Data were analyzed using the FMRIB Software Library and BioImageSuite.

Results

Analyses of the DTI data revealed white matter alterations approaching statistical significance in all supratentorial lobes. Statistically significant group differences (sNSC < control group) in mean diffusivity were localized to the right supramarginal gyrus. Analysis of the resting-state seed in relation to whole-brain data revealed significant increases in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y, z]: −6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the sNSC group relative to controls. Furthermore, in the sNSC patients versus controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left angular gyrus (MNI coordinates −31, −61, 34), posterior cingulate cortex (MNI coordinates 13, −52, 18), precuneus (MNI coordinates 10, −55, 54), left and right parahippocampus (MNI coordinates −13, −52, 2 and MNI coordinates 11, −50, 2, respectively), lingual (MNI coordinates −11, −86, −10), and fusiform gyri (MNI coordinates −30, −79, −18). Intrinsic connectivity analysis also revealed altered connectivity between central nodes in the default mode network in sNSC relative to controls; the left and right posterior cingulate cortices (MNI coordinates −5, −35, 34 and MNI coordinates 6, −42, 39, respectively) were negatively correlated to right hemisphere precuneus (MNI coordinates 6, −71, 46), while the left ventromedial prefrontal cortex (MNI coordinates 6, 34, −8) was negatively correlated to right middle frontal gyrus (MNI coordinates 40, 4, 33). All group comparisons (sNSC vs controls) were conducted at a whole brain–corrected threshold of p < 0.05.

Conclusions

This study demonstrates altered neocortical structural and functional connectivity in sNSC that may, in part or substantially, underlie the neuropsychological deficits commonly reported in this population. Future studies combining analysis of multimodal MRI and clinical characterization data in larger samples of participants are warranted.

Abbreviations used in this paper:

BA = Brodmann area; DMN = default mode network; DTI = diffusion tensor imaging; MNI = Montreal Neurological Institute; NSC = nonsyndromic craniosynostosis; ROI = region of interest; rs-fcMRI = resting-state functional connectivity MRI; sNSC = sagittal NSC; WISC-III = Wechsler Intelligence Scale for Children 3rd edition.

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  • 1

    Becker DB, , Petersen JD, , Kane AA, , Cradock MM, , Pilgram TK, & Marsh JL: Speech, cognitive, and behavioral outcomes in nonsyndromic craniosynostosis. Plast Reconstr Surg 116:400407, 2005

    • Search Google Scholar
    • Export Citation
  • 2

    Bogousslavsky J, , Miklossy J, , Deruaz JP, , Assal G, & Regli F: Lingual and fusiform gyri in visual processing: a clinicopathologic study of superior altitudinal hemianopia. J Neurol Neurosurg Psychiatry 50:607614, 1987

    • Search Google Scholar
    • Export Citation
  • 3

    Borkowska AR, , Francuz P, , Soluch P, & Wolak T: Brain activation in teenagers with isolated spelling disorder during tasks involving spelling assessment and comparison of pseudo-words. fMRI study. Brain Dev [epub ahead of print], 2013

    • Search Google Scholar
    • Export Citation
  • 4

    Buckner RL, , Andrews-Hanna JR, & Schacter DL: The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:138, 2008

    • Search Google Scholar
    • Export Citation
  • 5

    Castellanos FX, , Margulies DS, , Kelly C, , Uddin LQ, , Ghaffari M, & Kirsch A, et al.: Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 63:332337, 2008

    • Search Google Scholar
    • Export Citation
  • 6

    Cavanna AE, & Trimble MR: The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129:564583, 2006

  • 7

    Chan JW, , Stewart CL, , Stalder MW, , St Hilaire H, , McBride L, & Moses MH: Endoscope-assisted versus open repair of craniosynostosis: a comparison of perioperative cost and risk. J Craniofac Surg 24:170174, 2013

    • Search Google Scholar
    • Export Citation
  • 8

    Derderian C, & Seaward J: Syndromic craniosynostosis. Semin Plast Surg 26:6475, 2012

  • 9

    Eckert MA, , Hu D, , Eliez S, , Bellugi U, , Galaburda A, & Korenberg J, et al.: Evidence for superior parietal impairment in Williams syndrome. Neurology 64:152153, 2005

    • Search Google Scholar
    • Export Citation
  • 10

    Fox MD, , Snyder AZ, , Vincent JL, , Corbetta M, , Van Essen DC, & Raichle ME: The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102:96739678, 2005

    • Search Google Scholar
    • Export Citation
  • 11

    Hampson M, , Driesen NR, , Skudlarski P, , Gore JC, & Constable RT: Brain connectivity related to working memory performance. J Neurosci 26:1333813343, 2006

    • Search Google Scholar
    • Export Citation
  • 12

    Horwitz B, , Rumsey JM, & Donohue BC: Functional connectivity of the angular gyrus in normal reading and dyslexia. Proc Natl Acad Sci U S A 95:89398944, 1998

    • Search Google Scholar
    • Export Citation
  • 13

    Jane JA, , Edgerton MT, , Futrell JW, & Park TS: Immediate correction of sagittal synostosis. J Neurosurg 49:705710, 1978

  • 14

    Jimenez DF, & Barone CM: Early treatment of anterior calvarial craniosynostosis using endoscopic-assisted minimally invasive techniques. Childs Nerv Syst 23:14111419, 2007

    • Search Google Scholar
    • Export Citation
  • 15

    Johnson MK, , Nolen-Hoeksema S, , Mitchell KJ, & Levin Y: Medial cortex activity, self-reflection and depression. Soc Cogn Affect Neurosci 4:313327, 2009

    • Search Google Scholar
    • Export Citation
  • 16

    Just MA, , Keller TA, , Malave VL, , Kana RK, & Varma S: Autism as a neural systems disorder: a theory of frontal-posterior underconnectivity. Neurosci Biobehav Rev 36:12921313, 2012

    • Search Google Scholar
    • Export Citation
  • 17

    Kapp-Simon KA, , Speltz ML, , Cunningham ML, , Patel PK, & Tomita T: Neurodevelopment of children with single suture craniosynostosis: a review. Childs Nerv Syst 23:269281, 2007

    • Search Google Scholar
    • Export Citation
  • 18

    Kolar JC: An epidemiological study of nonsyndromal craniosynostoses. J Craniofac Surg 22:4749, 2011

  • 19

    Korpilahti P, , Saarinen P, & Hukki J: Deficient language acquisition in children with single suture craniosynostosis and deformational posterior plagiocephaly. Childs Nerv Syst 28:419425, 2012

    • Search Google Scholar
    • Export Citation
  • 20

    Liddle EB, , Hollis C, , Batty MJ, , Groom MJ, , Totman JJ, & Liotti M, et al.: Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate. J Child Psychol Psychiatry 52:761771, 2011

    • Search Google Scholar
    • Export Citation
  • 21

    Magge SN, , Westerveld M, , Pruzinsky T, & Persing JA: Long-term neuropsychological effects of sagittal craniosynostosis on child development. J Craniofac Surg 13:99104, 2002

    • Search Google Scholar
    • Export Citation
  • 22

    Maguire EA, , Frith CD, , Burgess N, , Donnett JG, & O'Keefe J: Knowing where things are parahippocampal involvement in encoding object locations in virtual large-scale space. J Cogn Neurosci 10:6176, 1998

    • Search Google Scholar
    • Export Citation
  • 23

    Marrelec G, & Fransson P: Assessing the influence of different ROI selection strategies on functional connectivity analyses of fMRI data acquired during steady-state conditions. PLoS One 6:e14788, 2011

    • Search Google Scholar
    • Export Citation
  • 24

    McFadden KL, , Tregellas JR, , Shott ME, & Frank GK: Reduced salience and default mode network activity in women with anorexia nervosa. J Psychiatry Neurosci 38:130046, 2013

    • Search Google Scholar
    • Export Citation
  • 25

    Mundy P: Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system. J Child Psychol Psychiatry 44:793809, 2003

    • Search Google Scholar
    • Export Citation
  • 26

    Peng ZW, , Xu T, , He QH, , Shi CZ, , Wei Z, & Miao GD, et al.: Default network connectivity as a vulnerability marker for obsessive compulsive disorder. Psychol Med [epub ahead of print], 2013

    • Search Google Scholar
    • Export Citation
  • 27

    Petersen SE, & Posner MI: The attention system of the human brain: 20 years after. Annu Rev Neurosci 35:7389, 2012

  • 28

    Ridderinkhof KR, , Ullsperger M, , Crone EA, & Nieuwenhuis S: The role of the medial frontal cortex in cognitive control. Science 306:443447, 2004

    • Search Google Scholar
    • Export Citation
  • 29

    Rubia K, , Overmeyer S, , Taylor E, , Brammer M, , Williams SC, & Simmons A, et al.: Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. Am J Psychiatry 156:891896, 1999

    • Search Google Scholar
    • Export Citation
  • 30

    Rushworth MFS, , Walton ME, , Kennerley SW, & Bannerman DM: Action sets and decisions in the medial frontal cortex. Trends Cogn Sci 8:410417, 2004

    • Search Google Scholar
    • Export Citation
  • 31

    Sambataro F, , Wolf ND, , Pennuto M, , Vasic N, & Wolf RC: Revisiting default mode network function in major depression: evidence for disrupted subsystem connectivity. Psychol Med [epub ahead of print], 2013

    • Search Google Scholar
    • Export Citation
  • 32

    Schmidt SA, , Akrofi K, , Carpenter-Thompson JR, & Husain FT: Default mode, dorsal attention and auditory resting state networks exhibit differential functional connectivity in tinnitus and hearing loss. PLoS ONE 8:e76488, 2013

    • Search Google Scholar
    • Export Citation
  • 33

    Seghier ML: The angular gyrus: multiple functions and multiple subdivisions. Neuroscientist 19:4361, 2013

  • 34

    Sharma RK: Craniosynostosis. Indian J Plast Surg 46:1827, 2013

  • 35

    Shen X, , Tokoglu F, , Papademetris X, & Constable RT: Groupwise whole-brain parcellation from resting-state fMRI data for network node identification. Neuroimage 82:403415, 2013

    • Search Google Scholar
    • Export Citation
  • 36

    Shipster C, , Hearst D, , Somerville A, , Stackhouse J, , Hayward R, & Wade A: Speech, language, and cognitive development in children with isolated sagittal synostosis. Dev Med Child Neurol 45:3443, 2003

    • Search Google Scholar
    • Export Citation
  • 37

    Small DM, , Gitelman DR, , Gregory MD, , Nobre AC, , Parrish TB, & Mesulam MM: The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention. Neuroimage 18:633641, 2003

    • Search Google Scholar
    • Export Citation
  • 38

    Smith SM: Fast robust automated brain extraction. Hum Brain Mapp 17:143155, 2002

  • 39

    Smith SM, , Jenkinson M, , Johansen-Berg H, , Rueckert D, , Nichols TE, & Mackay CE, et al.: Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:14871505, 2006

    • Search Google Scholar
    • Export Citation
  • 40

    Smith SM, , Jenkinson M, , Woolrich MW, , Beckmann CF, , Behrens TE, & Johansen-Berg H, et al.: Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23:Suppl 1 S208S219, 2004

    • Search Google Scholar
    • Export Citation
  • 41

    Sonuga-Barke EJ, & Fairchild G: Neuroeconomics of attention-deficit/hyperactivity disorder: differential influences of medial, dorsal, and ventral prefrontal brain networks on suboptimal decision making?. Biol Psychiatry 72:126133, 2012

    • Search Google Scholar
    • Export Citation
  • 42

    Speltz ML, , Kapp-Simon K, , Collett B, , Keich Y, , Gaither R, & Cradock MM, et al.: Neurodevelopment of infants with single-suture craniosynostosis: presurgery comparisons with case-matched controls. Plast Reconstr Surg 119:18741881, 2007

    • Search Google Scholar
    • Export Citation
  • 43

    Volz KG, , Schubotz RI, & von Cramon DY: Variants of uncertainty in decision-making and their neural correlates. Brain Res Bull 67:403412, 2005

    • Search Google Scholar
    • Export Citation
  • 44

    Wang K, , Liang M, , Wang L, , Tian L, , Zhang X, & Li K, et al.: Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study. Hum Brain Mapp 28:967978, 2007

    • Search Google Scholar
    • Export Citation
  • 45

    Watanabe T, , Hirose S, , Wada H, , Imai Y, , Machida T, & Shirouzu I, et al.: A pairwise maximum entropy model accurately describes resting-state human brain networks. Nat Commun 4:1370, 2013

    • Search Google Scholar
    • Export Citation
  • 46

    Wechsler D: WISC-III: Wechsler Intelligence Scale for Children ed 3 San Antonio, TX, Psychological Corporation, 1991

  • 47

    Whitfield-Gabrieli S, & Ford JM: Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol 8:4976, 2012

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