Abstract
There is growing consensus that atypical cognitive and behavioral function in ASD is associated with abnormalities in brain network organization. This chapter reviews the anatomical and functional evidence on connectivity in ASD from diffusion tensor imaging (DTI) and functional connectivity MRI (FCMRI) studies. DTI studies overwhelmingly present evidence of white matter compromise across virtually all major fiber tracts of the brain in children and adults with ASD (although infants show a different pattern of early white matter development). While many FCMRI studies have found underconnectivity in ASD, others have reported diffuse overconnectivity. Both types of findings may reflect a reduced differentiation of networks in ASD. However, the field has been hampered by lack of methodological awareness, which is necessary to avoid misleading generalizations. Functional and anatomical connectivity have often been studied in isolation in the past, but a combination of imaging techniques will be necessary for a more comprehensive understanding of the impact of abnormal connectivity on cognitive processing in ASD.
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References
Alexander AL, Lee JE, Lazar M, Boudos R, Dubray MB, Oakes TR, Miller JN, Lu J, Jeong EK, McMahon WM, Bigler ED, Lainhart JE. Diffusion tensor imaging of the corpus callosum in autism. Neuroimage. 2007;34:61–73.
Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31:137–45.
Ameis SH, Fan J, Rockel C, Voineskos AN, Lobaugh NJ, Soorya L, Wang AT, Hollander E, Anagnostou E. Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study. PLoS One. 2011;6:e28044.
Anderson JS, Druzgal TJ, Froehlich A, DuBray MB, Lange N, Alexander AL, Abildskov T, Nielsen JA, Cariello AN, Cooperrider JR, Bigler ED, Lainhart JE. Decreased interhemispheric functional connectivity in autism. Cereb Cortex. 2011a;21:1134–46.
Anderson JS, Nielsen JA, Froehlich AL, DuBray MB, Druzgal TJ, Cariello AN, Cooperrider JR, Zielinski BA, Ravichandran C, Fletcher PT, Alexander AL, Bigler ED, Lange N, Lainhart JE. Functional connectivity magnetic resonance imaging classification of autism. Brain. 2011b;134:3742–54.
Assaf M, Jagannathan K, Calhoun VD, Miller L, Stevens MC, Sahl R, O’Boyle JG, Schultz RT, Pearlson GD. Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients. Neuroimage. 2010;53:247–56.
Barnea-Goraly N, Kwon H, Menon V, Eliez S, Lotspeich L, Reiss AL. White matter structure in autism: preliminary evidence from diffusion tensor imaging. Biol Psychiatry. 2004;55:323–6.
Beacher FD, Minati L, Baron-Cohen S, Lombardo MV, Lai MC, Gray MA, Harrison NA, Critchley HD. Autism attenuates sex differences in brain structure: a combined voxel-based morphometry and diffusion tensor imaging study. AJNR Am J Neuroradiol. 2012;33:83–9.
Ben Bashat D, Kronfeld-Duenias V, Zachor DA, Ekstein PM, Hendler T, Tarrasch R, Even A, Levy Y, Ben Sira L. Accelerated maturation of white matter in young children with autism: a high b value DWI study. Neuroimage. 2007;37:40–7.
Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34:537–41.
Carper RA, Moses P, Tigue ZD, Courchesne E. Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage. 2002;16:1038–51.
Castelli F, Frith C, Happe F, Frith U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain. 2002;125:1839–49.
Cheon KA, Kim YS, Oh SH, Park SY, Yoon HW, Herrington J, Nair A, Koh YJ, Jang DP, Kim YB, Leventhal BL, Cho ZH, Castellanos FX, Schultz RT. Involvement of the anterior thalamic radiation in boys with high functioning autism spectrum disorders: a Diffusion Tensor Imaging study. Brain Res. 2011;1417:77–86.
Cherkassky VL, Kana RK, Keller TA, Just MA. Functional connectivity in a baseline resting-state network in autism. Neuroreport. 2006;17:1687–90.
Chugani D. Autism. In: Ernst M, Rumsey J, editors. The foundation and future of functional neuroimaging in child psychiatry. New York: Cambridge University Press; 2000. p. 171–88.
Cole DM, Smith SM, Beckmann CF. Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Front Syst Neurosci. 2010;4:8.
Conturo TE, Williams DL, Smith CD, Gultepe E, Akbudak E, Minshew NJ. Neuronal fiber pathway abnormalities in autism: an initial MRI diffusion tensor tracking study of hippocampo-fusiform and amygdalo-fusiform pathways. J Int Neuropsychol Soc. 2008;14:933–46.
Cordes D, Haughton VM, Arfanakis K, Carew JD, Turski PA, Moritz CH, Quigley MA, Meyerand ME. Frequencies contributing to functional connectivity in the cerebral cortex in “resting-state” data. AJNR Am J Neuroradiol. 2001;22:1326–33.
Courchesne E, Pierce K. Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol. 2005;15:225–30.
Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988;318:1349–54.
Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45.
Damasio AR, Maurer RG. A neurological model for childhood autism. Arch Neurol. 1978;35:777–86.
Di Martino A, Kelly C, Grzadzinski R, Zuo XN, Mennes M, Mairena MA, Lord C, Castellanos FX, Milham MP. Aberrant striatal functional connectivity in children with autism. Biol Psychiatry. 2011;69:847–56.
Dinstein I, Pierce K, Eyler L, Solso S, Malach R, Behrmann M, Courchesne E. Disrupted neural synchronization in toddlers with autism. Neuron. 2011;70:1218–25.
Dosenbach NU, Fair DA, Miezin FM, Cohen AL, Wenger KK, Dosenbach RA, Fox MD, Snyder AZ, Vincent JL, Raichle ME, Schlaggar BL, Petersen SE. Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci U S A. 2007;104:11073–8.
Ebisch SJ, Gallese V, Willems RM, Mantini D, Groen WB, Romani GL, Buitelaar JK, Bekkering H. Altered intrinsic functional connectivity of anterior and posterior insula regions in high-functioning participants with autism spectrum disorder. Hum Brain Mapp. 2011;32:1013–28.
Fair DA, Schlaggar BL, Cohen AL, Miezin FM, Dosenbach NU, Wenger KK, Fox MD, Snyder AZ, Raichle ME, Petersen SE. A method for using blocked and event-related fMRI data to study “resting state” functional connectivity. Neuroimage. 2007;35:396–405.
Fletcher PT, Whitaker RT, Tao R, DuBray MB, Froehlich A, Ravichandran C, Alexander AL, Bigler ED, Lange N, Lainhart JE. Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism. Neuroimage. 2010;51:1117–25.
Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8:700–11.
Fox MD, Corbetta M, Snyder AZ, Vincent JL, Raichle ME. Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proc Natl Acad Sci U S A. 2006;103:10046–51.
Frazier TW, Hardan AY. A meta-analysis of the corpus callosum in autism. Biol Psychiatry. 2009;66:935–41.
Friston KJ, Price CJ. Dynamic representations and generative models of brain function. Brain Res Bull. 2001;54:275–85.
Friston KJ, Frith CD, Frackowiak RSJ. Time-dependent changes in effective connectivity measured with PET. Hum Brain Mapp. 1993;1:69–79.
Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003;100:253–8.
Hampson M, Peterson BS, Skudlarski P, Gatenby JC, Gore JC. Detection of functional connectivity using temporal correlations in MR images. Hum Brain Mapp. 2002;15:247–62.
Honey CJ, Kotter R, Breakspear M, Sporns O. Network structure of cerebral cortex shapes functional connectivity on multiple time scales. Proc Natl Acad Sci USA. 2007;104:10240–5.
Honey CJ, Sporns O, Cammoun L, Gigandet X, Thiran JP, Meuli R, Hagmann P. Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci USA. 2009;106:2035–40.
Hong S, Ke X, Tang T, Hang Y, Chu K, Huang H, Ruan Z, Lu Z, Tao G, Liu Y. Detecting abnormalities of corpus callosum connectivity in autism using magnetic resonance imaging and diffusion tensor tractography. Psychiatry Res. 2011;194:333–9.
Horwitz B, Rumsey JM, Grady CL, Rapoport SI. The cerebral metabolic landscape in autism: intercorrelations of regional glucose utilization. Arch Neurol. 1988;45:749–55.
Ipser JC, Syal S, Bentley J, Adnams CM, Steyn B, Stein DJ. 1H-MRS in autism spectrum disorders: a systematic meta-analysis. Metab Brain Dis. 2012;27:275–87.
Johnson MH. Interactive specialization: a domain-general framework for human functional brain development. Dev Cogn Neurosci. 2011;1:7–21.
Jones TB, Bandettini PA, Kenworthy L, Case LK, Milleville SC, Martin A, Birn RM. Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder. Neuroimage. 2010;49:401–14.
Jou RJ, Mateljevic N, Kaiser MD, Sugrue DR, Volkmar FR, Pelphrey KA. Structural neural phenotype of autism: preliminary evidence from a diffusion tensor imaging study using tract-based spatial statistics. AJNR Am J Neuroradiol. 2011;32:1607–13.
Just MA, Cherkassky VL, Keller TA, Minshew NJ. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain. 2004;127:1811–21.
Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ. Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb Cortex. 2007;17:951–61.
Kana RK, Keller TA, Cherkassky VL, Minshew NJ, Just MA. Sentence comprehension in autism: thinking in pictures with decreased functional connectivity. Brain. 2006;129:2484–93.
Kana RK, Keller TA, Minshew NJ, Just MA. Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks. Biol Psychiatry. 2007;62:198–206.
Kana RK, Keller TA, Cherkassky VL, Minshew NJ, Adam Just M. Atypical frontal-posterior synchronization of theory of mind regions in autism during mental state attribution. Soc Neurosci. 2009;4:135–52.
Keehn B, Shih P, Brenner L, Townsend J, Müller R-A. Functional connectivity for an “island of sparing” in autism spectrum disorder: an fMRI study of visual search. Hum Brain Mapp. 2012 (in press).
Kennedy DP, Courchesne E. The intrinsic functional organization of the brain is altered in autism. Neuroimage. 2008;39:1877–85.
Kleinhans NM, Richards T, Sterling L, Stegbauer KC, Mahurin R, Johnson LC, Greenson J, Dawson G, Aylward E. Abnormal functional connectivity in autism spectrum disorders during face processing. Brain. 2008;131:1000–12.
Koshino H, Carpenter PA, Minshew NJ, Cherkassky VL, Keller TA, Just MA. Functional connectivity in an fMRI working memory task in high-functioning autism. Neuroimage. 2005;24:810–21.
Le Bihan D. Looking into the functional architecture of the brain with diffusion MRI. Nat Rev Neurosci. 2003;4:469–80.
Lee PS, Yerys BE, Della Rosa A, Foss-Feig J, Barnes KA, James JD, VanMeter J, Vaidya CJ, Gaillard WD, Kenworthy LE. Functional connectivity of the inferior frontal cortex changes with age in children with autism spectrum disorders: a FCMRI study of response inhibition. Cereb Cortex. 2009;19:1787–94.
Lewis CM, Baldassarre A, Committeri G, Romani GL, Corbetta M. Learning sculpts the spontaneous activity of the resting human brain. Proc Natl Acad Sci USA. 2009;106:17558–63.
Lo YC, Soong WT, Gau SS, Wu YY, Lai MC, Yeh FC, Chiang WY, Kuo LW, Jaw FS, Tseng WY. The loss of asymmetry and reduced interhemispheric connectivity in adolescents with autism: a study using diffusion spectrum imaging tractography. Psychiatry Res. 2011;192:60–6.
Logothetis NK, Pfeuffer J. On the nature of the BOLD fMRI contrast mechanism. Magn Reson Imaging. 2004;22:1517–31.
Lombardo MV, Chakrabarti B, Bullmore ET, Sadek SA, Pasco G, Wheelwright SJ, Suckling J, Baron-Cohen S. Atypical neural self-representation in autism. Brain. 2010;133:611–24.
Lowe MJ, Dzemidzic M, Lurito JT, Mathews VP, Phillips MD. Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections. Neuroimage. 2000;12:582–7.
Mason RA, Williams DL, Kana RK, Minshew N, Just MA. Theory of mind disruption and recruitment of the right hemisphere during narrative comprehension in autism. Neuropsychologia. 2008;46:269–80.
Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.
Mesulam MM. Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol. 1990;28:597–613.
Mizuno A, Villalobos ME, Davies MM, Dahl BC, Müller R-A. Partially enhanced thalamo-cortical functional connectivity in autism. Brain Res. 2006;1104:160–74.
Monk CS, Peltier SJ, Wiggins JL, Weng SJ, Carrasco M, Risi S, Lord C. Abnormalities of intrinsic functional connectivity in autism spectrum disorders. Neuroimage. 2009;47:764–72.
Mostofsky SH, Powell SK, Simmonds DJ, Goldberg MC, Caffo B, Pekar JJ. Decreased connectivity and cerebellar activity in autism during motor task performance. Brain. 2009;132:2413–25.
Mountcastle VB. The columnar organization of the neocortex. Brain. 1997;120(Pt 4):701–22.
Müller R-A. Functional connectivity. In: Volkmar F, editor. Encyclopedia of autism spectrum disorders. New York: Springer (in press).
Müller R-A, Shih P, Keehn B, Deyoe JR, Leyden KM, Shukla DK. Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders. Cereb Cortex. 2011;21:2233–43.
Nagae LM, Zarnow DM, Blaskey L, Dell J, Khan SY, Qasmieh S, Levy SE, Roberts TP. Elevated mean diffusivity in the left hemisphere superior longitudinal fasciculus in autism spectrum disorders increases with more profound language impairment. AJNR Am J Neuroradiol. 2012;33:1720–25.
Nir Y, Hasson U, Levy I, Yeshurun Y, Malach R. Widespread functional connectivity and fMRI fluctuations in human visual cortex in the absence of visual stimulation. Neuroimage. 2006;30:1313–24.
Noonan SK, Haist F, Müller R-A. Aberrant functional connectivity in autism: Evidence from low-frequency BOLD signal fluctuations. Brain Res. 2009;1262:48–63.
Pardini M, Garaci FG, Bonzano L, Roccatagliata L, Palmieri MG, Pompili E, Coniglione F, Krueger F, Ludovici A, Floris R, Benassi F, Emberti Gialloreti L. White matter reduced streamline coherence in young men with autism and mental retardation. Eur J Neurol. 2009;16:1185–90.
Passingham RE, Stephan KE, Kotter R. The anatomical basis of functional localization in the cortex. Nat Rev Neurosci. 2002;3:606–16.
Philip RC, Dauvermann MR, Whalley HC, Baynham K, Lawrie SM, Stanfield AC. A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders. Neurosci Biobehav Rev. 2011;36:901–42.
Pierce K, Müller RA, Ambrose J, Allen G, Courchesne E. Face processing occurs outside the fusiform “face area” in autism: evidence from functional MRI. Brain. 2001;124:2059–73.
Pierce K, Haist F, Sedaghat F, Courchesne E. The brain response to personally familiar faces in autism: findings of fusiform activity and beyond. Brain. 2004;127:2703–16.
Piven J, Arndt S. The cerebellum and autism. Neurology. 1995;45:398–402.
Poustka L, Jennen-Steinmetz C, Henze R, Vomstein K, Haffner J, Sieltjes B. Fronto-temporal disconnectivity and symptom severity in children with autism spectrum disorder. World J Biol Psychiatry. 2012;13:269–80.
Redcay E. The superior temporal sulcus performs a common function for social and speech perception: implications for the emergence of autism. Neurosci Biobehav Rev. 2008;32:123–42.
Rudie JD, Shehzad Z, Hernandez LM, Colich NL, Bookheimer SY, Iacoboni M, Dapretto M. Reduced functional integration and segregation of distributed neural systems underlying social and emotional information processing in autism spectrum disorders. Cereb Cortex. 2012;22:1025–37.
Rutter M. The development of infantile autism. Psychol Med. 1974;4:147–63.
Sadaghiani S, Hesselmann G, Friston KJ, Kleinschmidt A. The relation of ongoing brain activity, evoked neural responses, and cognition. Front Syst Neurosci. 2010;4:20.
Schölvinck ML, Maier A, Ye FQ, Duyn JH, Leopold DA. Neural basis of global resting-state fMRI activity. Proc Natl Acad Sci U S A. 2010;107:10238–43.
Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F, Skudlarski P, Lacadie C, Cohen DJ, Gore JC. Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome [see comments]. Arch Gen Psychiatry. 2000;57:331–40.
Shen MD, Shih P, Öttl B, Keehn BM, Leyden KM, Gaffrey MS, Müller R-A. Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity. Neuroimage. 2012;62:1780–91.
Shih P, Shen M, Öttl B, Keehn B, Gaffrey MS, Müller R-A. Atypical network connectivity for imitation in autism spectrum disorder. Neuropsychologia. 2010;48:2931–9.
Shih P, Keehn B, Oram JK, Leyden KM, Keown CL, Müller R-A. Functional differentiation of posterior superior temporal sulcus in autism: a functional connectivity magnetic resonance imaging study. Biol Psychiatry. 2011;70:270–7.
Shukla DK, Keehn B, Lincoln AJ, Müller R-A. White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study. J Am Acad Child Adolesc Psychiatry. 2010;49:1269–78, 1278 e1261–62.
Shukla DK, Keehn B, Smylie DM, Müller R-A. Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder. Neuropsychologia. 2011;49:1378–82.
Sivaswamy L, Kumar A, Rajan D, Behen M, Muzik O, Chugani D, Chugani H. A diffusion tensor imaging study of the cerebellar pathways in children with autism spectrum disorder. J Child Neurol. 2010;25:1223–31.
Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR, Beckmann CF. Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci U S A. 2009;106:13040–5.
Solomon M, Ozonoff SJ, Ursu S, Ravizza S, Cummings N, Ly S, Carter CS. The neural substrates of cognitive control deficits in autism spectrum disorders. Neuropsychologia. 2009;47:2515–26.
Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT, Chugani DC. Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cereb Cortex. 2008;18:2659–65.
Turner KC, Frost L, Linsenbardt D, McIlroy JR, Müller R-A. Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism. Behav Brain Funct. 2006;2:34–45.
Van Dijk KR, Hedden T, Venkataraman A, Evans KC, Lazar SW, Buckner RL. Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization. J Neurophysiol. 2010;103:297–321.
Villalobos ME, Mizuno A, Dahl BC, Kemmotsu N, Müller R-A. Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism. Neuroimage. 2005;25:916–25.
Vissers ME, Cohen MX, Geurts HM. Brain connectivity and high functioning autism: a promising path of research that needs refined models, methodological convergence, and stronger behavioral links. Neurosci Biobehav Rev. 2012;36:604–25.
Weinstein M, Ben-Sira L, Levy Y, Zachor DA, Ben Itzhak E, Artzi M, Tarrasch R, Eksteine PM, Hendler T, Ben Bashat D. Abnormal white matter integrity in young children with autism. Hum Brain Mapp. 2011;32:534–43.
Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S, Bullmore E. Functional disconnectivity of the medial temporal lobe in Asperger’s syndrome. Biol Psychiatry. 2005;57:991–8.
Wicker B, Fonlupt P, Hubert B, Tardif C, Gepner B, Deruelle C. Abnormal cerebral effective connectivity during explicit emotional processing in adults with autism spectrum disorder. Soc Cogn Affect Neurosci. 2008;3:135–43.
Wolff JJ, Gu H, Gerig G, Elison JT, Styner M, Gouttard S, Botteron KN, Dager SR, Dawson G, Estes AM, Evans AC, Hazlett HC, Kostopoulos P, McKinstry RC, Paterson SJ, Schultz RT, Zwaigenbaum L, Piven J. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry. 2012;169:589–600.
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Work on this chapter was supported by the National Institutes of Health (R01-MH081023, R01-DC006155).
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Müller, RA. (2014). Anatomical and Functional Connectivity in Autism Spectrum Disorders. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_192
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