Neuroimaging Insights into Autism Spectrum Disorder: Structural and Functional Brain
Autism Spectrum Disorder (ASD) is a condition that affects social communication, behavior, and interests. This review analyzes recent brain imaging studies to understand the biological basis of ASD. Studies using structural magnetic resonance imaging (sMRI) show that people with ASD often have less gray matter in key brain areas like the amygdala and superior temporal sulcus. There are also concerns with white matter connections in the brain. Functional magnetic resonance imaging (fMRI)studies show reduced connectivity within critical brain networks and irregular activation patterns when processing social information. Intervention studies suggest that targeted training can improve brain function related to social skills. Postmortem research reveals cellular and synaptic changes, such as fewer Purkinje cells and altered neuron organization. These findings highlight the importance of studying the social brain network in ASD and suggest the need for more long-term, comprehensive studies. This review is intended to contribute to the development of advanced diagnostic tools and therapies that will ultimately enhance the quality of life for individuals with ASD.
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Publishing; 2013. doi:10.1176/appi.books.9780890425596
2. Lord C, Risi S, Lambrecht L, et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000;30(3):205-223. doi:10.1023/A:1005592401947
3. Rutter M, Le Couteur A, Lord C. Autism Diagnostic Interview-Revised. Western Psychological Services; 2003.
4. Ecker C, Bookheimer SY, Murphy DGM. Neuroimaging in autism spectrum disorder: Brain structure and function across the lifespan. The Lancet Neurology. 2012;14(11):1121-1134. doi:10.1016/S1474-4422(15)00050-2
5. Hazlett HC, Gu H, Munsell BC, et al. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017;542(7641):348-351. doi:10.1038/nature21369
6. Maximo JO, Cadena EJ, Kana RK. The implications of brain connectivity in the neuropsychology of autism. Neuropsychology Review. 2014;24(1):16-31. doi:10.1007/s11065-014-9250-0
7. Haxby JV, Hoffman EA, Gobbini MI. The distributed human neural system for face perception. Trends in Cognitive Sciences. 2000;4(6):223-233. doi:10.1016/S1364-6613(00)01482-0
8. Adolphs R. Neural systems for recognizing emotion. Current Opinion in Neurobiology. 2002;12(2):169-177. doi:10.1016/S0959-4388(02)00301-X
9. Ecker C. The neuroanatomy of autism spectrum disorder: An overview of structural neuroimaging findings and their translatability to the clinical setting. Autism. 2017;21(1):18-28. doi:10.1177/1362361315627136
10. van Rooij D, Anagnostou E, Arango C, et al. Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group. Am J Psychiatry. 2018;175(4):359-369. doi:10.1176/appi.ajp.2017.17010100
11. Müller RA, Fishman I. Brain connectivity and neuroimaging of social networks in autism. Trends in Cognitive Sciences. 2018;22(12):1103-1116. doi:10.1016/j.tics.2018.09.008
12. Padmanabhan A, Lynch CJ, Schaer M, Menon V. The default mode network in autism. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2017;2(6):476-486.
13. Bailey A, Luthert P, Dean A, et al. A clinicopathological study of autism. Brain. 1998;121(Pt 5):889-905. doi:10.1093/brain/121.5.889
14. Morgan JT, Barger N, Amaral DG, Schumann CM, Courchesne E. Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder. PLoS ONE. 2010;5(11):e13747.
15. Baron-Cohen S, Leslie AM, Frith U. Does the autistic child have a “theory of mind”? Cognition. 1985;21(1):37-46. doi:10.1016/0010-0277(85)90022-8
16. Loukusa S, Moilanen I. Pragmatic inference abilities in individuals with Asperger syndrome or high-functioning autism: A review. Research in Autism Spectrum Disorders. 2009;3(4):890-904. doi:10.1016/j.rasd.2009.05.002
17. Schurz M, Radua J, Aichhorn M, Richlan F, Perner J. Fractionating theory of mind: A meta-analysis of functional brain imaging studies. Neuroscience & Biobehavioral Reviews. 2014;42:9-34. doi:10.1016/j.neubiorev.2014.01.009
18. Hoffman EA, Haxby JV. Distinct representations of eye gaze and identity in the distributed human neural system for face perception. Nature Neuroscience. 2000;3(1):80-84. doi:10.1038/71152
19. Kuperberg GR, McGuire PK, Bullmore ET, et al. Common and distinct neural substrates for pragmatic, semantic, and syntactic processing of spoken sentences: an fMRI study. J Cogn Neurosci. 2000;12(2):321-341. doi:10.1162/089892900562138
20. Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2001;290(3):337-344. doi:10.1001/jama.290.3.337
21. Schumann CM, Bloss CS, Barnes CC, et al. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. Journal of Neuroscience. 2010;30(12):4419-4427. doi:10.1523/JNEUROSCI.5714-09.2010
22. Márquez-García AV, Ng BK, Iarocci G, Moreno S, Vakorin VA, Doesburg SM. Atypical Associations between Functional Connectivity during Pragmatic and Semantic Language Processing and Cognitive Abilities in Children with Autism. Brain Sci. 2023;13(10):1448. doi:10.3390/brainsci13101448
23. Lainhart JE. Advances in autism neuroimaging research for the clinician and geneticist. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2006;142(1):33-39. doi:10.1002/ajmg.c.30080
24. Sato W, Toichi M, Uono S, Kochiyama T. Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders. BMC Neurosci. 2012;13:99. doi:10.1186/1471-2202-13-99
25. Pereira AM, Campos BM, Coan AC, et al. Differences in Cortical Structure and Functional MRI Connectivity in High Functioning Autism. Front Neurol. 2018;9:539. doi:10.3389/fneur.2018.00539
26. Lo YC, Chen YJ, Hsu YC, Tseng WI, Gau SS. Reduced tract integrity of the model for social communication is a neural substrate of social communication deficits in autism spectrum disorder. J Child Psychol Psychiatry. 2017;58(5):576-585. doi:10.1111/jcpp.12641
27. d’Albis MA, Rolls ET, Collignon O, Wicker B. Reduced superior longitudinal fasciculus fiber density in the left hemisphere mediates autism-social dysfunction symptoms and language abilities in children. Journal of Autism and Developmental Disorders. 2018;48(2):240-251.
28. d’Albis MA, Guevara P, Guevara M, et al. Local structural connectivity is associated with social cognition in autism spectrum disorder. Brain. 2018;141(12):3472-3481. doi:10.1093/brain/awy275
29. Odriozola P, Uddin LQ, Lynch CJ, Kochalka J, Chen T, Menon V. Insula response and connectivity during social and non-social attention in children with autism. Social Cognitive and Affective Neuroscience. 2018;11(2):334-344.
30. Fishman I, Müller RA. The Default Mode Network and the Social Brain Hypothesis of Autism Spectrum Disorder. Frontiers in Human Neuroscience. 2018;12:155.
31. Ciaramidaro A, Bölte S, Schlitt S, et al. Transdiagnostic deviant facial recognition for implicit negative emotion in autism and schizophrenia. Eur Neuropsychopharmacol. 2018;28(2):264-275. doi:10.1016/j.euroneuro.2017.12.005
32. Sato W, Kochiyama T, Uono S, Yoshimura S, Toichi M. Neural Mechanisms Underlying Conscious and Unconscious Gaze-Triggered Attentional Orienting in Autism Spectrum Disorder. Front Hum Neurosci. 2017;11:339. doi:10.3389/fnhum.2017.00339
33. Yang YJD, Allen T, Abdullahi SM, Pelphrey KA, Volkmar FR, Chapman SB. Neural mechanisms of behavioral change in young adults with high-functioning autism receiving virtual reality social cognition training: A pilot study. Autism Res. 2018;11(5):713-725. doi:10.1002/aur.1941
34. Kana RK, Keller TA, Minshew NJ, Just MA. Inhibitory control in high-functioning autism: Decreased activation and underconnectivity in inhibition networks. Biological Psychiatry. 2015;62(3):198-206. doi:10.1016/j.biopsych.2006.08.004
35. Ciaramidaro A, Bölte S, Schlitt S, et al. Transdiagnostic deviant facial recognition for implicit negative emotion in autism spectrum disorder. PLoS One. 2015;10(3):e0121450.
36. 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. Neuroscience & Biobehavioral Reviews. 2012;36(2):901-942. doi:10.1016/j.neubiorev.2011.10.008
37. Patriquin MA, DeRamus T, Libero LE, Laird A, Kana RK. Neuroanatomical and neurofunctional markers of social cognition in autism spectrum disorder. Human Brain Mapping. 2016;37(11):3957-3978. doi:10.1002/hbm.23288
38. Bašnáková J, Weber K, Petersson KM, van Berkum J, Hagoort P. Beyond the language given: The neural correlates of inferring speaker meaning. Cerebral Cortex. 2014;24(10):2572-2583. doi:10.1093/cercor/bht112
39. Mosconi MW, Cody-Hazlett H, Poe MD, Gerig G, Gimpel Smith R. Longitudinal study of amygdala volume and joint attention in 2- to 4-year-old children with autism. Archives of General Psychiatry. 2009;66(5):509-516. doi:10.1001/archgenpsychiatry.2009.19
40. Schumann CM, Hamstra J, Goodlin-Jones BL, et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci. 2004;24(28):6392-6401. doi:10.1523/JNEUROSCI.1297-04.2004
41. Bonilha L, Cendes F, Rorden C, et al. Gray and white matter imbalance--typical structural abnormality underlying classic autism? Brain Dev. 2008;30(6):396-401. doi:10.1016/j.braindev.2007.11.006
42. Courchesne E, Townsend J, Akshoomoff NA, et al. Impairment in shifting attention in autistic and cerebellar patients. Behav Neurosci. 1994;108(5):848-865. doi:10.1037/0735-7044.108.5.848
43. Kaufmann WE, Cooper KL, Mostofsky SH, et al. Specificity of cerebellar vermian abnormalities in autism: a quantitative magnetic resonance imaging study. J Child Neurol. 2003;18(7):463-470. doi:10.1177/08830738030180070501
44. Hardan AY, Jou RJ, Keshavan MS, Varma R, Minshew NJ, Sahin M. Increased frontal cortical folding in autism: A preliminary MRI study. Psychiatry Research: Neuroimaging. 2006;164(1):83-89.
45. Wallace GL, Eisenberg IW, Robustelli B, et al. Longitudinal cortical development during adolescence and young adulthood in autism spectrum disorder: increased cortical thinning but comparable surface area changes. J Am Acad Child Adolesc Psychiatry. 2015;54(6):464-469. doi:10.1016/j.jaac.2015.03.007
46. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67-81. doi:10.1002/ana.20315
47. Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolumnar pathology in autism. Neurology. 2002;58(3):428-432. doi:10.1212/WNL.58.3.428
48. Buxhoeveden DP, Semendeferi K, Buckwalter J, Schenker N, Switzer R, Courchesne E. Reduced minicolumns in the frontal cortex of patients with autism. Neuropathol Appl Neurobiol. 2006;32(5):483-491. doi:10.1111/j.1365-2990.2006.00745.x
49. Martínez-Cerdeño V. Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models. Dev Neurobiol. 2017;77(4):393-404. doi:10.1002/dneu.22417
50. Castelli F, Frith C, Happé F, Frith U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain. 2002;125(Pt 8):1839-1849. doi:10.1093/brain/awf189
51. Weng SJ, Wiggins JL, Peltier SJ, et al. Alterations of resting state functional connectivity in the default network in adolescents with autism spectrum disorders. Brain Research. 2010;1313:202-214. doi:10.1016/j.brainres.2009.11.057
52. Dalton KM, Nacewicz BM, Johnstone T, et al. Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci. 2005;8(4):519-526. doi:10.1038/nn1421
53. Green HL, Shuffrey LC, Levinson L, et al. Evaluation of mismatch negativity as a marker for language impairment in autism spectrum disorder. J Commun Disord. 2020;87:105997. doi:10.1016/j.jcomdis.2020.105997
54. Verhoeven JS, De Cock P, Lagae L, Sunaert S. Neuroimaging of autism. Neuroradiology. 2010;52:3-14. doi:10.1007/s00234-009-0583-y
55. Pierce K. Early Functional Brain Development in Autism and the Promise of Sleep fMRI. Brain Research. 2011;1380:162-174. doi:10.1016/j.brainres.2010.09.028
56. Gabrielsen TP, Anderson JS, Stephenson KG, et al. Functional MRI connectivity of children with autism and low verbal and cognitive performance. Molecular Autism. 2018;9(1):67. doi:10.1186/s13229-018-0248-y
57. Schumann CM, Nordahl CW. Bridging the Gap between MRI and Postmortem Research in Autism. Brain Research. 2011;1380:175-186. doi:10.1016/j.brainres.2010.09.061
58. Faizo NL. A narrative review of MRI changes correlated to signs and symptoms of autism. Medicine. 2022;101(34):e30059. doi:10.1097/MD.0000000000030059
59. Rafiee F, Habibabadi RR, Motaghi M, Yousem DM, Yousem IJ. Brain MRI in Autism Spectrum Disorder: Narrative Review and Recent Advances. Journal of Magnetic Resonance Imaging. 2021;55(6):1613-1624. doi:10.1002/jmri.27949
60. Duvall L, May KE, Waltz A, Kana RK. The neurobiological map of theory of mind and pragmatic communication in autism. Social Neuroscience. 2023;18(4):191-204. doi:10.1080/17470919.2023.2242095
61. Doe J. Functional neuroimaging and childhood autism. Journal of Autism Research. 2023;1(1):1-7.
62. Brambilla P, Hardan A, Ucelli di Nemi S, Perez J, Soares JC, Barale F. Brain anatomy and development in autism: review of structural MRI studies. Brain Research Bulletin. 2003;61(5):557-569. doi:10.1016/j.brainresbull.2003.06.001
63. Cole EJ, Barraclough NE, Andrews TJ. Reduced connectivity between mentalizing and mirror systems in autism spectrum condition. Neuropsychologia. 2019;122:88-97. doi:10.1016/j.neuropsychologia.2018.11.008