Abstract
Semantic processing impairments are present in a proportion of individuals with autism spectrum disorder (ASD). Despite the numerous imaging studies investigating this language domain in ASD, there is a lack of consensus regarding the brain structures showing abnormal pattern of activity. This meta-analysis aimed to identify neural activation patterns present during semantic processing in ASD. Findings reveal activation of areas associated with semantic processing and executive functions in ASD. However, the activation was less concise in comparison to controls and there was less activation in the right hemisphere and in areas associated with executive functions. This provides strong support for impaired semantic processing in ASD that is consistently associated with abnormal patterns of neural activity in the semantic network.
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References
Agt, H. V., Verhoeven, L., Brink, G. V. D., & Koning, H. D. (2011). The impact on socio-emotional development and quality of life of language impairment in 8-year-old children. Developmental Medicine & Child Neurology, 53(1), 81–88. https://doi.org/10.1111/j.1469-8749.2010.03794.x.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Association. https://doi.org/10.1176/appi.books.9780890425596.
Ardila, A., Bernal, B., & Rosselli, M. (2016). How localized are language brain areas? A review of Brodmann areas involvement in oral language. Archives of Clinical Neuropsychology, 31(1), 112–122. https://doi.org/10.1093/arclin/acv081.
Bastian, A. J., & Thach, W. T. (1995). Cerebellar outflow lesions: A comparison of movement deficits resulting from lesions at the levels of the cerebellum and thalamus. Annals of Neurology, 38(6), 881–892. https://doi.org/10.1002/ana.410380608.
Bednarz, H. M., Maximo, J. O., Murdaugh, D. L., O’Kelley, S., & Kana, R. K. (2017). “Decoding versus comprehension”: Brain responses underlying reading comprehension in children with autism. Brain and Language, 169, 39–47. https://doi.org/10.1016/j.bandl.2017.01.002.
Boddaert, N., Belin, P., Chabane, N., Poline, J.-B., Barthélémy, C., Mouren-Simeoni, M.-C., Brunelle, F., Samson, Y., & Zilbovicius, M. (2003). Perception of complex sounds: Abnormal pattern of cortical activation in autism. The American Journal of Psychiatry, 160(11), 2057–2060. https://doi.org/10.1176/appi.ajp.160.11.2057.
Bookheimer, S. (2002). Functional MRI of language: New approaches to understanding the cortical organization of semantic processing. Annual Review of Neuroscience, 25(1), 151–188. https://doi.org/10.1146/annurev.neuro.25.112701.142946.
Brignell, A., Morgan, A. T., Woolfenden, S., Klopper, F., May, T., Sarkozy, V., & Williams, K. (2018). A systematic review and meta-analysis of the prognosis of language outcomes for individuals with autism spectrum disorder. Autism & Developmental Language Impairments, 3, 239694151876761. https://doi.org/10.1177/2396941518767610.
Coderre, E. L., Chernenok, M., Gordon, B., & Ledoux, K. (2017). Linguistic and non-linguistic semantic processing in individuals with autism spectrum disorders: An ERP study. Journal of Autism and Developmental Disorders, 47(3), 795–812. https://doi.org/10.1007/s10803-016-2985-0.
Corbett, F., Jefferies, E., & Ralph, M. A. L. (2009). Exploring multimodal semantic control impairments in semantic aphasia: Evidence from naturalistic object use. Neuropsychologia, 47(13), 2721–2731. https://doi.org/10.1016/j.neuropsychologia.2009.05.020.
Courchesne, E., Townsend, J., Akshoomoff, N. A., Saitoh, O., Yeung-Courchesne, R., Lincoln, A. J., James, H. E., Haas, R. H., Schreibman, L., & Lau, L. (1994). Impairment in shifting attention in autistic and cerebellar patients. Behavioral Neuroscience, 108(5), 848–865. https://doi.org/10.1037//0735-7044.108.5.848.
Dunn, M. A., & Bates, J. C. (2005). Developmental change in neutral processing of words by children with autism. Journal of Autism and Developmental Disorders, 35(3), 361–376. https://doi.org/10.1007/s10803-005-3304-3.
Eickhoff, S. B., Bzdok, D., Laird, A. R., Kurth, F., & Fox, P. T. (2012). Activation likelihood estimation meta-analysis revisited. NeuroImage, 59(3), 2349–2361. https://doi.org/10.1016/j.neuroimage.2011.09.017.
Eickhoff, S. B., Laird, A. R., Grefkes, C., Wang, L. E., Zilles, K., & Fox, P. T. (2009). Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: A random-effects approach based on empirical estimates of spatial uncertainty. Human Brain Mapping, 30(9), 2907–2926. https://doi.org/10.1002/hbm.20718.
Eickhoff, S. B., Nichols, T. E., Laird, A. R., Hoffstaedter, F., Amunts, K., Fox, P. T., Bzdok, D., & Eickhoff, C. R. (2016). Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation. NeuroImage, 137, 70–85. https://doi.org/10.1016/j.neuroimage.2016.04.072.
Erdler, M., Beisteiner, R., Mayer, D., Kaindl, T., Edward, V., Windischberger, C., Lindinger, G., & Deecke, L. (2000). Supplementary motor area activation preceding voluntary movement is detectable with a whole-scalp magnetoencephalography system. NeuroImage, 11(6 Pt 1), 697–707. https://doi.org/10.1006/nimg.2000.0579.
Fiez, J. A., Petersen, S. E., Cheney, M. K., & Raichle, M. E. (1992). Impaired non-motor learning and error detection associated with cerebellar damagea single case study. Brain, 115(1), 155–178. https://doi.org/10.1093/brain/115.1.155.
Friederici, A. D., Rüschemeyer, S.-A., Hahne, A., & Fiebach, C. J. (2003). The role of left inferior frontal and superior temporal cortex in sentence comprehension: Localizing syntactic and semantic processes. Cerebral Cortex (New York, N.Y.: 1991), 13(2), 170–177.
Gasparini, M., Di Piero, V., Ciccarelli, O., Cacioppo, M. M., Pantano, P., & Lenzi, G. L. (1999). Linguistic impairment after right cerebellar stroke: A case report. European Journal of Neurology, 6(3), 353–356. https://doi.org/10.1046/j.1468-1331.1999.630353.x.
Gervais, H., Belin, P., Boddaert, N., Leboyer, M., Coez, A., Sfaello, I., Barthélémy, C., Brunelle, F., Samson, Y., & Zilbovicius, M. (2004). Abnormal cortical voice processing in autism. Nature Neuroscience, 7(8), 801–802. https://doi.org/10.1038/nn1291.
Gutchess, A. H., Hedden, T., Ketay, S., Aron, A., & Gabrieli, J. D. E. (2010). Neural differences in the processing of semantic relationships across cultures. Social Cognitive and Affective Neuroscience, 5(2–3), 254–263. https://doi.org/10.1093/scan/nsp059.
Hahne, A., Eckstein, K., & Friederici, A. D. (2004). Brain signatures of syntactic and semantic processes during children’s language development. Journal of Cognitive Neuroscience, 16(7), 1302–1318. https://doi.org/10.1162/0898929041920504.
Herringshaw, A. J., Ammons, C. J., DeRamus, T. P., & Kana, R. K. (2016). Hemispheric differences in language processing in autism spectrum disorders: A meta-analysis of neuroimaging studies. Autism Research, 9(10), 1046–1057. https://doi.org/10.1002/aur.1599.
Howard, D., Patterson, K., Wise, R., Brown, W. D., Friston, K., Weiller, C., & Frackowiak, R. (1992). The cortical localization of the lexicons. Positron emission tomography evidence. Brain: A Journal of Neurology, 115(Pt 6), 1769–1782.
Jackson, R. L., Hoffman, P., Pobric, G., & Ralph, M. A. L. (2016). The semantic network at work and rest: Differential connectivity of anterior temporal lobe subregions. Journal of Neuroscience, 36(5), 1490–1501. https://doi.org/10.1523/JNEUROSCI.2999-15.2016.
Jefferies, E., & Lambon Ralph, M. A. (2006). Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain: A Journal of Neurology, 129(Pt 8), 2132–2147. https://doi.org/10.1093/brain/awl153.
Jefferies, E., Patterson, K., & Ralph, M. A. L. (2008). Deficits of knowledge versus executive control in semantic cognition: Insights from cued naming. Neuropsychologia, 46(2), 649–658. https://doi.org/10.1016/j.neuropsychologia.2007.09.007.
Joseph, J., Noble, K., & Eden, G. (2001). The neurobiological basis of reading. Journal of Learning Disabilities, 34(6), 566–579. https://doi.org/10.1177/002221940103400609.
Jueptner, M., Rijntjes, M., Weiller, C., Faiss, J. H., Timmann, D., Mueller, S. P., & Diener, H. C. (1995). Localization of a cerebellar timing process using PET. Neurology, 45(8), 1540–1545. https://doi.org/10.1212/wnl.45.8.1540.
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: A Journal of Neurology, 127(Pt 8), 1811–1821. https://doi.org/10.1093/brain/awh199.
Kamio, Y., & Toichi, M. (2000). Dual access to semantics in autism: Is pictorial access superior to verbal access? Journal of Child Psychology and Psychiatry, and Allied Disciplines, 41(7), 859–867.
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: A Journal of Neurology, 129(Pt 9), 2484–2493. https://doi.org/10.1093/brain/awl164.
Kang, A. M., Constable, R. T., Gore, J. C., & Avrutin, S. (1999). An event-related fMRI study of implicit phrase-level syntactic and semantic processing. NeuroImage, 10(5), 555–561. https://doi.org/10.1006/nimg.1999.0493.
Keren-Happuch, E., Chen, S.-H. A., Ho, M.-H. R., & Desmond, J. E. (2014). A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies. Human Brain Mapping, 35(2), 593–615. https://doi.org/10.1002/hbm.22194.
Klein, A. P., Ulmer, J. L., Quinet, S. A., Mathews, V., & Mark, L. P. (2016). Nonmotor functions of the cerebellum: An introduction. AJNR. American Journal of Neuroradiology, 37(6), 1005–1009. https://doi.org/10.3174/ajnr.A4720.
Knaus, T. A., Silver, A. M., Kennedy, M., Lindgren, K. A., Dominick, K. C., Siegel, J., & Tager-Flusberg, H. (2010). Language laterality in autism spectrum disorder and typical controls: A functional, volumetric, and diffusion tensor MRI study. Brain and Language, 112(2), 113. https://doi.org/10.1016/j.bandl.2009.11.005.
Knaus, T. A., Silver, A. M., Lindgren, K. A., Hadjikhani, N., & Tager-Flusberg, H. (2008). FMRI activation during a language task in adolescents with ASD. Journal of the International Neuropsychological Society: JINS, 14(6), 967–979. https://doi.org/10.1017/S1355617708081216.
Koyama, M. S., Di Martino, A., Zuo, X.-N., Kelly, C., Mennes, M., Jutagir, D. R., Castellanos, F. X., & Milham, M. P. (2011). Resting-state functional connectivity indexes reading competence in children and adults. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 31(23), 8617–8624. https://doi.org/10.1523/JNEUROSCI.4865-10.2011.
Kuperberg, G. R., McGuire, P. K., Bullmore, E. T., Brammer, M. J., Rabe-Hesketh, S., Wright, I. C., Lythgoe, D. J., Williams, S. C., & David, A. S. (2000). Common and distinct neural substrates for pragmatic, semantic, and syntactic processing of spoken sentences: An fMRI study. Journal of Cognitive Neuroscience, 12(2), 321–341. https://doi.org/10.1162/089892900562138.
Kutas, M., & Federmeier, K. D. (2011). Thirty years and counting: Finding meaning in the N400 component of the event related brain potential (ERP). Annual Review of Psychology, 62, 621–647. https://doi.org/10.1146/annurev.psych.093008.131123.
Kutas, M., Hillyard, S. A., & Gazzaniga, M. S. (1988). Processing of semantic anomaly by right and left hemispheres of commissurotomy patients. Evidence from event-related brain potentials. Brain: A Journal of Neurology, 111(Pt 3), 553–576. https://doi.org/10.1093/brain/111.3.553.
Lai, M.-C., Lombardo, M. V., & Baron-Cohen, S. (2014). Autism. Lancet (London, England), 383(9920), 896–910. https://doi.org/10.1016/S0140-6736(13)61539-1.
Laird, A. R., Robinson, J. L., McMillan, K. M., Tordesillas-Gutiérrez, D., Moran, S. T., Gonzales, S. M., Ray, K. L., Franklin, C., Glahn, D. C., Fox, P. T., & Lancaster, J. L. (2010). Comparison of the disparity between Talairach and MNI coordinates in functional neuroimaging data: Validation of the Lancaster transform. NeuroImage, 51(2), 677–683. https://doi.org/10.1016/j.neuroimage.2010.02.048.
Lau, E. F., Phillips, C., & Poeppel, D. (2008). A cortical network for semantics: (De)constructing the N400. Nature Reviews Neuroscience, 9(12), 920–933. https://doi.org/10.1038/nrn2532.
Laufer, I., Negishi, M., Lacadie, C. M., Papademetris, X., & Constable, R. T. (2011). Dissociation between the activity of the right middle frontal gyrus and the middle temporal gyrus in processing semantic priming. PLOS ONE, 6(8), e22368. https://doi.org/10.1371/journal.pone.0022368.
Leung, H.-C., Gore, J. C., & Goldman-Rakic, P. S. (2002). Sustained mnemonic response in the human middle frontal gyrus during on-line storage of spatial memoranda. Journal of Cognitive Neuroscience, 14(4), 659–671. https://doi.org/10.1162/08989290260045882.
Liddle, P. F., Kiehl, K. A., & Smith, A. M. (2001). Event-related fMRI study of response inhibition. Human Brain Mapping, 12(2), 100–109.
McCleery, J. P., Ceponiene, R., Burner, K. M., Townsend, J., Kinnear, M., & Schreibman, L. (2010). Neural correlates of verbal and nonverbal semantic integration in children with autism spectrum disorders. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 51(3), 277–286. https://doi.org/10.1111/j.1469-7610.2009.02157.x.
Moberget, T., Gullesen, E. H., Andersson, S., Ivry, R. B., & Endestad, T. (2014). Generalized role for the cerebellum in encoding internal models: Evidence from semantic processing. The Journal of Neuroscience, 34(8), 2871–2878. https://doi.org/10.1523/JNEUROSCI.2264-13.2014.
Mody, M., & Belliveau, J. W. (2013). Speech and language impairments in autism: Insights from behavior and neuroimaging. North American Journal of Medicine & Science, 5(3), 157–161.
Murdoch, B. E. (2010). The cerebellum and language: Historical perspective and review. Cortex; a Journal Devoted to the Study of the Nervous System and Behavior, 46(7), 858–868. https://doi.org/10.1016/j.cortex.2009.07.018.
Nachev, P., Wydell, H., O’neill, K., Husain, M., & Kennard, C. (2007). The role of the pre-supplementary motor area in the control of action. NeuroImage, 36(Suppl 2), T155–T163. https://doi.org/10.1016/j.neuroimage.2007.03.034.
Neumann, S., Quinting, J., Rosenkranz, A., de Beer, C., Jonas, K., & Stenneken, P. (2019). Quality of life in adults with neurogenic speech-language-communication difficulties: A systematic review of existing measures. Journal of Communication Disorders, 79, 24–45. https://doi.org/10.1016/j.jcomdis.2019.01.003.
Nicola, K., & Watter, P. (2015). Health-related quality of life from the perspective of children with severe specific language impairment. Health and Quality of Life Outcomes, 13. https://doi.org/10.1186/s12955-015-0326-1.
Noonan, K. A., Jefferies, E., Visser, M., & Lambon Ralph, M. A. (2013). Going beyond inferior prefrontal involvement in semantic control: Evidence for the additional contribution of dorsal angular gyrus and posterior middle temporal cortex. Journal of Cognitive Neuroscience, 25(11), 1824–1850. https://doi.org/10.1162/jocn_a_00442.
Oh, A., Duerden, E. G., & Pang, E. W. (2014). The role of the insula in speech and language processing. Brain and Language, 135, 96–103. https://doi.org/10.1016/j.bandl.2014.06.003.
Ojemann, G. A., & Whitaker, H. A. (1978). Language localization and variability. Brain and Language, 6(2), 239–260. https://doi.org/10.1016/0093-934X(78)90061-5.
Owen, A. M., McMillan, K. M., Laird, A. R., & Bullmore, E. (2005). N-back working memory paradigm: A meta-analysis of normative functional neuroimaging studies. Human Brain Mapping, 25(1), 46–59. https://doi.org/10.1002/hbm.20131.
Petersen, S. E., Fox, P. T., Posner, M. I., Mintun, M., & Raichle, M. E. (1988). Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature, 331(6157), 585–589. https://doi.org/10.1038/331585a0.
Petrides, M. (2005). Lateral prefrontal cortex: Architectonic and functional organization. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360(1456), 781–795. https://doi.org/10.1098/rstb.2005.1631.
Pijnacker, J., Geurts, B., van Lambalgen, M., Buitelaar, J., & Hagoort, P. (2010). Exceptions and anomalies: An ERP study on context sensitivity in autism. Neuropsychologia, 48(10), 2940–2951. https://doi.org/10.1016/j.neuropsychologia.2010.06.003.
Poldrack, R. A., Wagner, A. D., Prull, M. W., Desmond, J. E., Glover, G. H., & Gabrieli, J. D. E. (1999). Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex. NeuroImage, 10(1), 15–35. https://doi.org/10.1006/nimg.1999.0441.
Price, C. J. (2012). A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading. NeuroImage, 62(2), 816–847. https://doi.org/10.1016/j.neuroimage.2012.04.062.
Raij, T. (1999). Patterns of brain activity during visual imagery of letters. Journal of Cognitive Neuroscience, 11(3), 282–299.
Rapin, I., & Dunn, M. (1997). Language disorders in children with autism. Seminars in Pediatric Neurology, 4(2), 86–92. https://doi.org/10.1016/S1071-9091(97)80024-1.
Ribeiro, T., Valasek, C., Minati, L., & Boggio, P. (2013). Altered semantic integration in autism beyond language. Neuroreport, 24(8), 414–418. https://doi.org/10.1097/WNR.0b013e328361315e.
Samson, F., Zeffiro, T. A., Doyon, J., Benali, H., & Mottron, L. (2015). Speech acquisition predicts regions of enhanced cortical response to auditory stimulation in autism spectrum individuals. Journal of Psychiatric Research, 68, 285–292. https://doi.org/10.1016/j.jpsychires.2015.05.011.
Sur, S., & Sinha, V. K. (2009). Event-related potential: An overview. Industrial Psychiatry Journal, 18(1), 70–73. https://doi.org/10.4103/0972-6748.57865.
Tager-Flusberg, H., Paul, R., & Lord, C. (2005). Language and communication in autism. In Handbook of autism and pervasive developmental disorders: Diagnosis, development, neurobiology, and behavior (Vol. 1, 3rd ed., pp. 335–364). Hoboken, NJ: John Wiley & Sons Inc..
Tesink, C. M. J. Y., Buitelaar, J. K., Petersson, K. M., van der Gaag, R. J., Teunisse, J.-P., & Hagoort, P. (2011). Neural correlates of language comprehension in autism spectrum disorders: When language conflicts with world knowledge. Neuropsychologia, 49(5), 1095–1104. https://doi.org/10.1016/j.neuropsychologia.2011.01.018.
Thompson, R. F. (1988). The neural basis of basic associative learning of discrete behavioral responses. Trends in Neurosciences, 11(4), 152–155. https://doi.org/10.1016/0166-2236(88)90141-5.
Toichi, M., & Kamio, Y. (2002). Long-term memory and levels-of-processing in autism. Neuropsychologia, 40(7), 964–969.
Toichi, M., & Kamio, Y. (2003). Long-term memory in high-functioning autism: Controversy on episodic memory in autism reconsidered. Journal of Autism and Developmental Disorders, 33(2), 151–161.
Turkeltaub, P. E., Eickhoff, S. B., Laird, A. R., Fox, M., Wiener, M., & Fox, P. (2012). Minimizing within-experiment and within-group effects in activation likelihood estimation meta-analyses. Human Brain Mapping, 33(1), 1–13. https://doi.org/10.1002/hbm.21186.
Wildgruber, D., Erb, M., Klose, U., & Grodd, W. (1997). Sequential activation of supplementary motor area and primary motor cortex during self-paced finger movement in human evaluated by functional MRI. Neuroscience Letters, 227(3), 161–164.
Williams, D. L., Cherkassky, V. L., Mason, R. A., Keller, T. A., Minshew, N. J., & Just, M. A. (2013). Brain function differences in language processing in children and adults with autism. Autism Research: Official Journal of the International Society for Autism Research, 6(4), 288–302. https://doi.org/10.1002/aur.1291.
Xiang, H., Lin, C., Ma, X., Zhang, Z., Bower, J. M., Weng, X., & Gao, J.-H. (2003). Involvement of the cerebellum in semantic discrimination: An fMRI study. Human Brain Mapping, 18(3), 208–214. https://doi.org/10.1002/hbm.10095.
Yelland, G. W. (1994). Word recognition and lexical access. In A. Bowers (Ed.). Encyclopedia of Language and Linguistics. Edinburgh: Pergamon Press.
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We would like to thank Zahra Emami for providing helpful comments and guidance while the manuscript was being prepared. An earlier version of this manuscript was submitted in partial fulfilment of a graduate course credit by the first author.
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L.P. conceived and planned the analysis. L.P carried out the literature search and the analyses. L.P, C.A. and E.P. contributed to interpretation of results. L.P took the lead in writing the manuscript, and all authors provided feedback and contributed to the final version of the manuscript. C.A supervised the project.
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Phan, L., Tariq, A., Lam, G. et al. The Neurobiology of Semantic Processing in Autism Spectrum Disorder: An Activation Likelihood Estimation Analysis. J Autism Dev Disord 51, 3266–3279 (2021). https://doi.org/10.1007/s10803-020-04794-9
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DOI: https://doi.org/10.1007/s10803-020-04794-9