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Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status

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Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with prominent impairments in sociocommunicative abilities, which have been linked to anomalous brain network organization. Despite ample evidence of atypical long-distance connectivity, the literature on local connectivity remains small and divergent. We used resting-state functional MRI regional homogeneity (ReHo) as a local connectivity measure in comparative analyses across several well-matched low-motion subsamples from the Autism Brain Imaging Data Exchange and in-house data, with a grand total of 147 ASD and 184 typically developing (TD) participants, ages 7–18 years. We tested for group differences in each subsample, with additional focus on the difference between eyes-open and eyes-closed resting states. Despite selection of highest quality data and tight demographic and motion matching between groups and across samples, few effects in exactly identical loci (voxels) were found across samples. However, there was gross consistency across all eyes-open samples of local overconnectivity (ASD > TD) in posterior, visual regions. There was also gross consistency of local underconnectivity (ASD < TD) in cingulate gyrus, although exact loci varied between mid/posterior and anterior sections. While all eyes-open datasets showed the described gross similarities, the pattern of group differences for participants scanned with eyes closed was different, with local overconnectivity in ASD in posterior cingulate gyrus, but underconnectivity in some visual regions. Our findings suggest that fMRI local connectivity measures may be relatively susceptible to site and cohort variability and that some previous inconsistencies in the ASD ReHo literature may be reconciled by more careful consideration of eye status.

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References

  • Abbott, A. E., Nair, A., Keown, C. L., Datko, M. C., Jahedi, A., Fishman, I., & Müller, R.-A. (2015). Patterns of atypical functional connectivity and behavioral links in autism differ between default, salience, and executive networks. Cerebral Cortex, 26, 4034.

    Article  PubMed  Google Scholar 

  • Agam, Y., Joseph, R. M., Barton, J. J., & Manoach, D. S. (2010). Reduced cognitive control of response inhibition by the anterior cingulate cortex in autism spectrum disorders. NeuroImage, 52(1), 336–347.

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson, J. S., Zielinski, B. A., Nielsen, J. A., & Ferguson, M. A. (2014). Complexity of low-frequency blood oxygen level-dependent fluctuations covaries with local connectivity. Human Brain Mapping, 35(4), 1273–1283.

    Article  PubMed  Google Scholar 

  • Assaf, M., Jagannathan, K., Calhoun, V. D., Miller, L., Stevens, M. C., Sahl, R., O'Boyle, J. G., Schultz, R. T., & Pearlson, G. D. (2010). Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients. NeuroImage, 53(1), 247–256.

    Article  PubMed  PubMed Central  Google Scholar 

  • Belmonte, M. K., Allen, G., Beckel-Mitchener, A., Boulanger, L. M., Carper, R. A., & Webb, S. J. (2004). Autism and abnormal development of brain connectivity. The Journal of Neuroscience, 24(42), 9228–9231.

    Article  CAS  PubMed  Google Scholar 

  • Brown, G. G., Mathalon, D. H., Stern, H., Ford, J., Mueller, B., Greve, D. N., et al. (2011). Multisite reliability of cognitive BOLD data. NeuroImage, 54(3), 2163–2175.

    Article  PubMed  Google Scholar 

  • Burrows, C. A., Laird, A. R., & Uddin, L. Q. (2016). Functional connectivity of brain regions for self- and other-evaluation in children, adolescents and adults with autism. Developmental Science, 19, 564.

    Article  PubMed  Google Scholar 

  • Casanova, M. F., van Kooten, I. A., Switala, A. E., van Engeland, H., Heinsen, H., Steinbusch, H. W., Hof, P. R., Trippe, J., Stone, J., & Schmitz, C. (2006). Minicolumnar abnormalities in autism. Acta Neuropathol (Berl), 112(3), 287–303.

    Article  Google Scholar 

  • Cerliani, L., Mennes, M., Thomas, R. M., Di Martino, A., Thioux, M., & Keysers, C. (2015). Increased functional connectivity between subcortical and cortical resting-state networks in autism Spectrum disorder. JAMA Psychiatry., 72, 767.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cox, R. W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29, 162–173.

  • Dajani D. R., Uddin L. Q. (2015) Local brain connectivity across development in autism spectrum disorder: A cross-sectional investigation. Autism research: official journal of the International Society for Autism Research. 9:43.

  • Dakin, S., & Frith, U. (2005). Vagaries of visual perception in autism. Neuron, 48(3), 497–507.

    Article  CAS  PubMed  Google Scholar 

  • Di Martino, A., Yan, C. G., Li, Q., Denio, E., Castellanos, F. X., Alaerts, K., Anderson, J. S., Assaf, M., Bookheimer, S. Y., Dapretto, M., Deen, B., Delmonte, S., Dinstein, I., Ertl-Wagner, B., Fair, D. A., Gallagher, L., Kennedy, D. P., Keown, C. L., Keysers, C., Lainhart, J. E., Lord, C., Luna, B., Menon, V., Minshew, N. J., Monk, C. S., Mueller, S., Müller, R. A., Nebel, M. B., Nigg, J. T., O'Hearn, K., Pelphrey, K. A., Peltier, S. J., Rudie, J. D., Sunaert, S., Thioux, M., Tyszka, J. M., Uddin, L. Q., Verhoeven, J. S., Wenderoth, N., Wiggins, J. L., Mostofsky, S. H., & Milham, M. P. (2014). The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Molecular Psychiatry, 19(6), 659–667.

    Article  CAS  PubMed  Google Scholar 

  • Dosenbach, N. U., Fair, D. A., Miezin, F. M., Cohen, A. L., Wenger, K. K., Dosenbach, R. A., Fox, M. D., Snyder, A. Z., Vincent, J. L., Raichle, M. E., Schlaggar, B. L., & Petersen, S. E. (2007). Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences of the United States of America, 104(26), 11073–11078.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doyle-Thomas K. A., Lee W., Foster N. E., Tryfon A., Ouimet T., Hyde K. L., Evans A. C., Lewis J., Zwaigenbaum L., Anagnostou E., NeuroDevNet A. S. D. I. G. (2015) Atypical functional brain connectivity during rest in autism spectrum disorders. Annals of Neurology, 77(5), 866–876.

  • Ebisch, S. J., Gallese, V., Willems, R. M., Mantini, D., Groen, W. B., Romani, G. L., Buitelaar, J. K., & Bekkering, H. (2011). Altered intrinsic functional connectivity of anterior and posterior insula regions in high-functioning participants with autism spectrum disorder. Human Brain Mapping, 32(7), 1013–1028.

    Article  PubMed  Google Scholar 

  • Eilam-Stock, T., Xu, P., Cao, M., Gu, X., Van Dam, N. T., Anagnostou, E., Kolevzon, A., Soorya, L., Park, Y., Siller, M., He, Y., Hof, P. R., & Fan, J. (2014). Abnormal autonomic and associated brain activities during rest in autism spectrum disorder. Brain, 137(Pt 1), 153–171.

    Article  PubMed  PubMed Central  Google Scholar 

  • Eussen, M. L., Gool, A. R., Louwerse, A., Verhulst, F. C., & Greaves-Lord, K. (2016). Superior disembedding performance in childhood predicts adolescent severity of repetitive behaviors: a seven years follow-up of individuals with autism Spectrum disorder. Autism research : official journal of the International Society for Autism Research, 9(2), 282–291.

    Article  Google Scholar 

  • Falahpour, M., Thompson, W. K., Abbott, A. E., Jahedi, A., Mulvey, M. E., Datko, M., Liu, T. T., & Müller, R. A. (2016). Underconnected, but not broken? Dynamic functional connectivity MRI shows underconnectivity in autism is linked to increased intra-individual variability across time. Brain Connectivity, 6(5), 403–414.

    Article  PubMed  PubMed Central  Google Scholar 

  • Forman, S. D., Cohen, J. D., Fitzgerald, M., Eddy, W. F., Mintun, M. A., & Noll, D. C. (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magnetic Resonance in Medicine, 33(5), 636–647.

    Article  CAS  PubMed  Google Scholar 

  • Friedman, L., Glover, G. H., & The FBIRN Consortium. (2006). Reducing interscanner variability of activation in a multicenter fMRI study: controlling for signal-to-fluctuation-noise-ratio (SFNR) differences. NeuroImage, 33(2), 471–481.

    Article  Google Scholar 

  • Friedman, L., Stern, H., Brown, G. G., Mathalon, D. H., Turner, J., Glover, G. H., et al. (2008). Test-retest and between-site reliability in a multicenter fMRI study. Human Brain Mapping, 29(8), 958–972.

    Article  PubMed  PubMed Central  Google Scholar 

  • Geschwind, D. H., & State, M. W. (2015). Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurology, 14, 1109.

    Article  PubMed  Google Scholar 

  • Gotts, S. J., Saad, Z. S., Jo, H. J., Wallace, G. L., Cox, R. W., & Martin, A. (2013). The perils of global signal regression for group comparisons: a case study of autism Spectrum disorders. Frontiers in Human Neuroscience, 7, 356.

    Article  PubMed  PubMed Central  Google Scholar 

  • Greicius, M. (2008). Resting-state functional connectivity in neuropsychiatric disorders. Current Opinion in Neurology, 21(4), 424–430.

    Article  PubMed  Google Scholar 

  • Happe, F. (1999). Autism: cognitive deficit or cognitive style? Trends in Cognitive Sciences, 3(6), 216–222.

    Article  CAS  PubMed  Google Scholar 

  • Horlin, C., Black, M., Falkmer, M., & Falkmer, T. (2016). Proficiency of individuals with autism spectrum disorder at disembedding figures: a systematic review. Developmental Neurorehabilitation, 19(1), 54–63.

    Article  PubMed  Google Scholar 

  • Itahashi, T., Yamada, T., Watanabe, H., Nakamura, M., Ohta, H., Kanai, C., Iwanami, A., Kato, N., & Hashimoto, R. (2015). Alterations of local spontaneous brain activity and connectivity in adults with high-functioning autism spectrum disorder. Molecular autism, 6, 30.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jao Keehn R. J., Sanchez S. S., Stewart C. R., Zhao W., Grenesko-Stevens E. L., Keehn B., Müller R.-A. (2016). Impaired downregulation of visual cortex during auditory processing is associated with autism symptomatology in children and adolescents with autism spectrum disorder. Autism research: official journal of the International Society for Autism Research.

  • Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage, 17(2), 825–841.

  • Jiang, L., Hou, X. H., Yang, N., Yang, Z., & Zuo, X. N. (2015). Examination of local functional homogeneity in autism. BioMed Research International, 2015, 174371.

    PubMed  PubMed Central  Google Scholar 

  • Joseph, R. M., Keehn, B., Connolly, C., Wolfe, J. M., & Horowitz, T. S. (2009). Why is visual search superior in autism spectrum disorder? Developmental Science, 12(6), 1083–1096.

    Article  PubMed  Google Scholar 

  • Just, M. A., Cherkassky, V. L., Keller, T. A., & Minshew, N. J. (2004). Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain, 127(Pt 8), 1811–1821.

    Article  PubMed  Google Scholar 

  • Kaldy, Z., Giserman, I., Carter, A. S., & Blaser, E. (2013). The mechanisms underlying the ASD advantage in visual search. Journal of Autism and Developmental Disorders, 46, 1513.

    Article  Google Scholar 

  • Kana, R. K., Keller, T. A., Cherkassky, V. L., Minshew, N. J., & Just, M. A. (2006). Sentence comprehension in autism: thinking in pictures with decreased functional connectivity. Brain, 129(Pt 9), 2484–2493.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kana, R. K., Keller, T. A., Minshew, N. J., & Just, M. A. (2007). Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks. Biological Psychiatry, 62(3), 198–206.

    Article  PubMed  Google Scholar 

  • Keehn, B., Brenner, L. A., Ramos, A. I., Lincoln, A. J., Marshall, S. P., & Müller, R.-A. (2009). Brief report: eye-movement patterns during an embedded figures test in children with ASD. Journal of Autism and Developmental Disorders, 39(2), 383–387.

    Article  PubMed  Google Scholar 

  • Keown, C. L., Shih, P., Nair, A., Peterson, N., & Müller, R.-A. (2013). Local functional overconnectivity in posterior brain regions is associated with symptom severity in autism spectrum disorders. Cell Reports, 5(3), 567–572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koldewyn, K., Yendiki, A., Weigelt, S., Gweon, H., Julian, J., Richardson, H., Malloy, C., Saxe, R., Fischl, B., & Kanwisher, N. (2014). Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder. Proceedings of the National Academy of Sciences of the United States of America, 111(5), 1981–1986.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leech, R., & Sharp, D. J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain, 137(Pt 1), 12–32.

    Article  PubMed  Google Scholar 

  • Liu, D., Dong, Z., Zuo, X., Wang, J., & Zang, Y. (2013). Eyes-open/eyes-closed dataset sharing for reproducibility evaluation of resting state fMRI data analysis methods. Neuroinformatics, 11(4), 469–476.

    Article  PubMed  Google Scholar 

  • Lopez-Larson, M. P., Anderson, J. S., Ferguson, M. A., & Yurgelun-Todd, D. (2011). Local brain connectivity and associations with gender and age. Developmental Cognitive Neuroscience, 1(2), 187–197.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.

  • Lord, C., Risi, S., Lambrecht, L., Cook, E. H. Jr., Leventhal, B. L., Dilavore, P. C., et al. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 05–223.

  • Lu, J. T., Kishida, K. T., De Asis-Cruz, J., Lohrenz, T., Treadwell-Deering, D., Beauchamp, M., & Montague, P. R. (2015). Single-stimulus functional MRI produces a neural individual difference measure for autism spectrum disorder. Clinical Psychological Science, 3(3), 422–432.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maximo, J. O., Keown, C. L., Nair, A., & Müller, R.-A. (2013). Approaches to local connectivity in autism using resting state functional connectivity MRI. Frontiers in Human Neuroscience, 7, 605.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maximo, J. O., Cadena, E. J., & Kana, R. K. (2014). The implications of brain connectivity in the neuropsychology of autism. Neuropsychology Review, 24(1), 16–31.

    Article  PubMed  PubMed Central  Google Scholar 

  • Minshew, N. J., & Williams, D. L. (2007). The new neurobiology of autism: cortex, connectivity, and neuronal organization. Archives of Neurology, 64(7), 945–950.

    Article  PubMed  PubMed Central  Google Scholar 

  • Monk, C. S., Peltier, S. J., Wiggins, J. L., Weng, S. J., Carrasco, M., Risi, S., & Lord, C. (2009). Abnormalities of intrinsic functional connectivity in autism spectrum disorders. NeuroImage, 47(2), 764–772.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mottron, L., Dawson, M., Soulieres, I., Hubert, B., & Burack, J. (2006). Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception. Journal of Autism and Developmental Disorders, 36(1), 27–43.

    Article  PubMed  Google Scholar 

  • Müller, R.-A. (2007). The study of autism as a distributed disorder. Mental Retardation and Developmental Disabilities Research Reviews, 13, 85–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller, R.-A., Shih, P., Keehn, B., Deyoe, J. R., Leyden, K. M., & Shukla, D. K. (2011). Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders. Cerebral Cortex, 21(10), 2233–2243.

    Article  PubMed  PubMed Central  Google Scholar 

  • Murphy, K., Birn, R. M., Handwerker, D. A., Jones, T. B., & Bandettini, P. A. (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? NeuroImage, 44(3), 893–905.

    Article  PubMed  Google Scholar 

  • Nair, A., Keown, C. L., Datko, M., Shih, P., Keehn, B., & Müller, R. A. (2014). Impact of methodological variables on functional connectivity findings in autism spectrum disorders. Human Brain Mapping, 35(8), 4035–4048.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nelson, S. B., & Valakh, V. (2015). Excitatory/inhibitory balance and circuit homeostasis in autism Spectrum disorders. Neuron, 87(4), 684–698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nomi, J. S., & Uddin, L. Q. (2015). Developmental changes in large-scale network connectivity in autism. NeuroImage Clinical, 7, 732–741.

    Article  PubMed  PubMed Central  Google Scholar 

  • Paakki, J. J., Rahko, J., Long, X., Moilanen, I., Tervonen, O., Nikkinen, J., Starck, T., Remes, J., Hurtig, T., Haapsamo, H., Jussila, K., Kuusikko-Gauffin, S., Mattila, M. L., Zang, Y., & Kiviniemi, V. (2010). Alterations in regional homogeneity of resting-state brain activity in autism spectrum disorders. Brain Research, 1321, 169.

    Article  CAS  PubMed  Google Scholar 

  • Palmen, S. J., van Engeland, H., Hof, P. R., & Schmitz, C. (2004). Neuropathological findings in autism. Brain, 127(Pt 12), 2572–2583.

    Article  PubMed  Google Scholar 

  • Patriat, R., Molloy, E. K., Meier, T. B., Kirk, G. R., Nair, V. A., Meyerand, M. E., Prabhakaran, V., & Birn, R. M. (2013). The effect of resting condition on resting-state fMRI reliability and consistency: a comparison between resting with eyes open, closed, and fixated. NeuroImage, 78, 463–473.

    Article  PubMed  PubMed Central  Google Scholar 

  • Power, J. D., Mitra, A., Laumann, T. O., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2014). Methods to detect, characterize, and remove motion artifact in resting state fMRI. NeuroImage, 84, 320–341.

    Article  PubMed  Google Scholar 

  • Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain, and Behavior, 2(5), 255–267.

    Article  CAS  PubMed  Google Scholar 

  • Rudie, J. D., & Dapretto, M. (2013). Convergent evidence of brain overconnectivity in children with autism? Cell Reports, 5(3), 565–566.

    Article  CAS  PubMed  Google Scholar 

  • Sampaio-Baptista, C., Filippini, N., Stagg, C. J., Near, J., Scholz, J., & Johansen-Berg, H. (2015). Changes in functional connectivity and GABA levels with long-term motor learning. NeuroImage, 106, 15–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samson, F., Mottron, L., Soulieres, I., & Zeffiro, T. A. (2012). Enhanced visual functioning in autism: an ALE meta-analysis. Human Brain Mapping, 33(7), 1553–1581.

    Article  PubMed  Google Scholar 

  • Satterthwaite, T. D., Elliott, M. A., Gerraty, R. T., Ruparel, K., Loughead, J., Calkins, M. E., Eickhoff, S. B., Hakonarson, H., Gur, R. C., Gur, R. E., & Wolf, D. H. (2013). An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data. Neuroimage, 64, 240–256.

  • Schipul, S. E., Keller, T. A., & Just, M. A. (2011). Inter-regional brain communication and its disturbance in autism. Frontiers in Systems Neuroscience, 5, 10.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schumann, C. M., & Nordahl, C. W. (2011). Bridging the gap between MRI and postmortem research in autism. Brain Research, 1380, 175–186.

    Article  CAS  PubMed  Google Scholar 

  • Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27(9), 2349–2356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen, M. D., Shih, P., Ottl, B., Keehn, B., Leyden, K. M., Gaffrey, M. S., & Muller, R. A. (2012). Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity. NeuroImage, 62(3), 1780–1791.

    Article  PubMed  Google Scholar 

  • Shih, P., Keehn, B., Oram, J. K., Leyden, K. M., Keown, C. L., & Müller, R.-A. (2011). Functional differentiation of posterior superior temporal sulcus in autism: a functional connectivity magnetic resonance imaging study. Biological Psychiatry, 70(3), 270–277.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shukla, D. K., Keehn, B. M., & Müller, R.-A. (2010). Regional homogeneity of fMRI time series in autism spectrum disorders. Neuroscience Letters, 476, 46–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simmons, D. R., Robertson, A. E., McKay, L. S., Toal, E., McAleer, P., & Pollick, F. E. (2009). Vision in autism spectrum disorders. Vision Research, 49(22), 2705–2739.

    Article  PubMed  Google Scholar 

  • Simms, M. L., Kemper, T. L., Timbie, C. M., Bauman, M. L., & Blatt, G. J. (2009). The anterior cingulate cortex in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups. Acta Neuropathologica, 118(5), 673–684.

    Article  PubMed  Google Scholar 

  • Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E., Johansen-Berg, H., et al. (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage, 23(Suppl. 1), S208–S219.

  • Spoormaker, V. I., Schroter, M. S., Gleiser, P. M., Andrade, K. C., Dresler, M., Wehrle, R., Samann, P. G., & Czisch, M. (2010). Development of a large-scale functional brain network during human non-rapid eye movement sleep. The Journal of Neuroscience, 30(34), 11379–11387.

    Article  CAS  PubMed  Google Scholar 

  • Sridharan, D., Levitin, D. J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences of the United States of America, 105(34), 12569–12574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stagg, C. J., Bachtiar, V., Amadi, U., Gudberg, C. A., Ilie, A. S., Sampaio-Baptista, C., O'Shea, J., Woolrich, M., Smith, S. M., Filippini, N., Near, J., & Johansen-Berg, H. (2014). Local GABA concentration is related to network-level resting functional connectivity. eLife, 3, e01465.

    Article  PubMed  PubMed Central  Google Scholar 

  • Supekar, K., Uddin, L. Q., Khouzam, A., Phillips, J., Gaillard, W. D., Kenworthy, L. E., Yerys, B. E., Vaidya, C. J., & Menon, V. (2013). Brain hyperconnectivity in children with autism and its links to social deficits. Cell Reports, 5(3), 738–747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutton, B. P., Goh, J., Hebrank, A., Welsh, R. C., Chee, M. W. L., & Park, D. C. (2008). Investigation and validation of intersite fMRI studies using the same imaging hardware. Journal of Magnetic Resonance Imaging, 28(1), 21–28.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tagliazucchi, E., von Wegner, F., Morzelewski, A., Borisov, S., Jahnke, K., & Laufs, H. (2012). Automatic sleep staging using fMRI functional connectivity data. NeuroImage, 63(1), 63–72.

    Article  PubMed  Google Scholar 

  • Turner, J. A., Damaraju, E., Van Erp, T. G. M., Mathalon, D. H., Ford, J. M., Voyvodic, J., et al. (2013). A multi-site resting state fMRI study on the amplitude of low frequency fluctuations in schizophrenia. Frontiers in Neuroscience, 7(7 AUG), 137.

    PubMed  PubMed Central  Google Scholar 

  • Uddin, L. Q., Supekar, K., Lynch, C. J., Khouzam, A., Phillips, J., Feinstein, C., Ryali, S., & Menon, V. (2013). Salience network-based classification and prediction of symptom severity in children with autism. JAMA Psychiatry, 70(8), 1–11.

    Article  Google Scholar 

  • Uppal, N., Wicinski, B., Buxbaum, J. D., Heinsen, H., Schmitz, C., & Hof, P. R. (2014). Neuropathology of the anterior midcingulate cortex in young children with autism. Journal of Neuropathology and Experimental Neurology, 73(9), 891–902.

    Article  PubMed  Google Scholar 

  • Vissers, M. E., Cohen, M. X., & Geurts, H. M. (2012). Brain connectivity and high functioning autism: a promising path of research that needs refined models, methodological convergence, and stronger behavioral links. Neuroscience and Biobehavioral Reviews, 36(1), 604–625.

    Article  PubMed  Google Scholar 

  • von dem Hagen, E. A., Stoyanova, R. S., Baron-Cohen, S., & Calder, A. J. (2013). Reduced functional connectivity within and between 'social' resting state networks in autism spectrum conditions. Social Cognitive and Affective Neuroscience, 8(6), 694–701.

    Article  Google Scholar 

  • Wang, X. H., Li, L., Xu, T., & Ding, Z. (2015). Investigating the temporal patterns within and between intrinsic connectivity networks under eyes-open and eyes-closed resting states: a dynamical functional connectivity study based on phase synchronization. PloS One, 10(10), e0140300.

    Article  PubMed  PubMed Central  Google Scholar 

  • Washington, S. D., Gordon, E. M., Brar, J., Warburton, S., Sawyer, A. T., Wolfe, A., Mease-Ference, E. R., Girton, L., Hailu, A., Mbwana, J., Gaillard, W. D., Kalbfleisch, M. L., & Vanmeter, J. W. (2013). Dysmaturation of the default mode network in autism. Human Brain Mapping, 35, 1284.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wass, S. (2011). Distortions and disconnections: disrupted brain connectivity in autism. Brain and Cognition, 75(1), 18–28.

    Article  PubMed  Google Scholar 

  • Yang, D. Y., Beam, D., Pelphrey, K. A., Abdullahi, S., & Jou, R. J. (2016). Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification. Molecular autism, 7, 11.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zang, Y., Jiang, T., Lu, Y., He, Y., & Tian, L. (2004). Regional homogeneity approach to fMRI data analysis. NeuroImage, 22(1), 394–400.

    Article  PubMed  Google Scholar 

  • Zhang, Y., Brady, M., & Smith, S. (2001). Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Transactions on Medical Imaging, 20, 45–57.

  • Zou, Q., Long, X., Zuo, X., Yan, C., Zhu, C., Yang, Y., Liu, D., He, Y., & Zang, Y. (2009). Functional connectivity between the thalamus and visual cortex under eyes closed and eyes open conditions: a resting-state fMRI study. Human Brain Mapping, 30(9), 3066–3078.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zou, Q., Miao, X., Liu, D., Wang, D. J., Zhuo, Y., & Gao, J. H. (2015). Reliability comparison of spontaneous brain activities between BOLD and CBF contrasts in eyes-open and eyes-closed resting states. NeuroImage, 121, 91–105.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, 6363 Alvarado Ct., Suite 200, San Diego, CA, 92120, USA

    Sangeeta Nair, R. Joanne Jao Keehn, Michael M. Berkebile, José Omar Maximo, Natalia Witkowska & Ralph-Axel Müller

  2. Department of Psychology, University of Alabama, Birmingham, AL, USA

    José Omar Maximo

  3. Joint Doctoral Program in Clinical Psychology, San Diego State University and University of California, San Diego, San Diego, CA, USA

    Ralph-Axel Müller

Authors
  1. Sangeeta Nair
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  2. R. Joanne Jao Keehn
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  3. Michael M. Berkebile
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  4. José Omar Maximo
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  5. Natalia Witkowska
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  6. Ralph-Axel Müller
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Corresponding author

Correspondence to Ralph-Axel Müller.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the appropriate institutional research boards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This study was supported by the National Institutes of Health R01 MH081023 (PI: RAM), K01 MH097972 (PI: Inna Fishman), and IMSD R25GM058906.

Conflict of interest

All authors declare that they have no conflict of interest related to the study presented here.

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Supplementary Fig. 1

Surface renderings of regional homogeneity differences between ASD and TD groups for each subsample from analyses without global signal regression and with non-standardized KCC-Z ReHo values (a), and without GSR and with standardized KCC ReHo values (b). In all supplementary figures, the two columns on the left depict the left hemisphere and the two columns on the right depict the right hemisphere (p < .05, corrected).

High resolution image (TIFF 87857 kb)

Supplementary Fig. 2

Surface renderings for direct comparison of ReHo between eyes open and eyes closed cohorts for ASD and TD groups without GSR and with non-standardized KCC-Z ReHo values (a) and without GSR and with standardized KCC ReHo values (b).

High resolution image (TIFF 33839 kb)

Supplementary Fig. 3

Surface renderings of regional homogeneity differences between ASD and TD groups (a), and between ABIDE eyes open and eyes closed cohorts shown separately for ASD and TD groups (b) for multi-site subsamples (with site and head motion included as nuisance covariates).

High resolution image (TIFF 56561 kb)

Supplementary Fig. 4

Surface renderings of regional homogeneity differences between ASD and TD groups for each subsample, limiting inclusion to sites contributing ≥10 participants per group.

High resolution image (TIFF 33297 kb)

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Nair, S., Jao Keehn, R.J., Berkebile, M.M. et al. Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status. Brain Imaging and Behavior 12, 168–179 (2018). https://doi.org/10.1007/s11682-017-9678-y

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  • DOI: https://doi.org/10.1007/s11682-017-9678-y

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