Volumetric Alterations in Brain Structures Caused by Autism during Different Age Stages

Abstract:

Conclusions in literature regarding the effect of Autism on the size of different brain structures are contradictory. The aim of this study is to determine the effect of Autism on the volumes of different brain subcortical structures, and the age stage at which those changes occur. 7 main brain structures were segmented and their volumes were obtained. Volumes and the ratio of the volume to total brain volume (SBR) were compared in Autism group to their corresponding values in Control group. Then, each group was divided into 4 subgroups based on age; the comparison was repeated for each subgroup. Independent t-test was used to determine if significant differences existed between compared groups. Significant reductions were observed in the SBR of Autistic Pallidum and Accumbens compared to Control group when considering the full range of ages (5–25 years). However, Amygdala’s volume was significantly smaller in Autism in the 5–8 year subgroup. In addition, the SBR of Putaman, Pallidum, Hippocampus, and Accumbens were reduced in the 18–25 year Autism subgroup. In conclusion, the alteration in the ratio of structure’s volume to total brain volume is a better indicator of Autism diagnosis than change in the absolute volume alone.

• Periodical: Journal of Biomimetics, Biomaterials and Biomedical Engineering (Volume 64)
• Pages: 95-104
• DOI: https://doi.org/10.4028/p-yjqi3J
• Online since: April 2024
• Authors: Ihssan S. Masad*, Lamis R. Banyissa, Ali Mohammad Alqudah
• Keywords: Aging, Autism, MRI, Neuroimaging

References

[1] T. Charman and G. Baird, "Practitioner review: Diagnosis of autism spectrum disorder in 2‐and 3‐year‐old children," J. Child Psychol. Psychiatry, 2002, 43 (3), 289–305.

DOI: 10.1111/1469-7610.00022

[2] C. Ecker, S. Y. Bookheimer, and D. G. M. Murphy, "Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan," Lancet Neurol., 2015, 14 (11), 1121–1134.

DOI: 10.1016/s1474-4422(15)00050-2

[3] M. Wang, D. Xu, L. Zhang, and H. Jiang, "Application of Multimodal MRI in the Early Diagnosis of Autism Spectrum Disorders: A Review," Diagnostics, 2023, 13 (19), 3027.

DOI: 10.3390/diagnostics13193027

[4] G. J. Katuwal, S. A. Baum, N. D. Cahill, and A. M. Michael, "Divide and conquer: sub-grouping of ASD improves ASD detection based on brain morphometry," PLoS One, 2016, 11 (4), e0153331.

DOI: 10.1371/journal.pone.0153331

[5] J. D. Herrington et al., "Amygdala volume differences in autism spectrum disorder are related to anxiety," J. Autism Dev. Disord., 2017, 47 (12), 3682–3691.

DOI: 10.1007/s10803-017-3206-1

[6] C. W. Nordahl et al., "Increased rate of amygdala growth in children aged 2 to 4 years with autism spectrum disorders: a longitudinal study," Arch. Gen. Psychiatry, 2012, 69 (1), 53–61.

DOI: 10.1001/archgenpsychiatry.2011.145

[7] B. M. Nacewicz et al., "Amygdala volume and nonverbal social impairment in adolescent and adult males with autism," Arch. Gen. Psychiatry, 2006, 63 (12), 1417–1428.

DOI: 10.1001/archpsyc.63.12.1417

[8] G. Li, et al., "Volumetric analysis of amygdala and hippocampal subfields for infants with autism," J Autism Dev Disord, 2023, 53 (6), 2475–2489

DOI: 10.1007/s10803-022-05535-w

[9] K. M. Dalton, B. M. Nacewicz, A. L. Alexander, and R. J. Davidson, "Gaze-fixation, brain activation, and amygdala volume in unaffected siblings of individuals with autism," Biol. Psychiatry, 2007, 61 (4), 512–520.

DOI: 10.1016/j.biopsych.2006.05.019

[10] D. Radeloff et al., "Structural alterations of the social brain: a comparison between schizophrenia and autism," PLoS One, 2014, 9 (9), e106539.

[11] Z. M. Saygin et al., "High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas," Neuroimage, 2017, 155, 370–382.

DOI: 10.1016/j.neuroimage.2017.04.046

[12] W. Zhang, W. Groen, M. Mennes, C. Greven, J. Buitelaar, and N. Rommelse, "Revisiting subcortical brain volume correlates of autism in the ABIDE dataset: effects of age and sex," Psychol. Med., 2018, 48 (4), 654–668.

DOI: 10.1017/s003329171700201x

[13] J. Munson et al., "Amygdalar volume and behavioral development in autism," Arch. Gen. Psychiatry, 2006, 63 (6), 686–693.

[14] D. Van Rooij 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: 10.26226/morressier.5785edd1d462b80296c9a207

[15] N. Barnea-Goraly et al., "A preliminary longitudinal volumetric MRI study of amygdala and hippocampal volumes in autism," Prog. Neuro-Psychopharmacology Biol. Psychiatry, 2014, 48, 124–128.

DOI: 10.1016/j.pnpbp.2013.09.010

[16] C. M. Schumann 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

[17] M. Barad, P.-W. Gean, and B. Lutz, "The role of the amygdala in the extinction of conditioned fear," Biol. Psychiatry, 2006, 60 (4), 322–328.

DOI: 10.1016/j.biopsych.2006.05.029

[18] T. Eilam-Stock, T. Wu, A. Spagna, L. J. Egan, and J. Fan, "Neuroanatomical alterations in high-functioning adults with autism spectrum disorder," Front. Neurosci., 2016, 10, 237.

DOI: 10.3389/fnins.2016.00237

[19] T. Yarkoni, R. A. Poldrack, T. E. Nichols, D. C. Van Essen, and T. D. Wager, "Large-scale automated synthesis of human functional neuroimaging data," Nat. Methods, 2011, 8 (8), 665–670.

DOI: 10.1038/nmeth.1635

[20] A. H. Turner, K. S. Greenspan, and T. G. M. van Erp, "Pallidum and lateral ventricle volume enlargement in autism spectrum disorder," Psychiatry Res. Neuroimaging, 2016, 252, 40–45.

DOI: 10.1016/j.pscychresns.2016.04.003

[21] B. F. Sparks et al., "Brain structural abnormalities in young children with autism spectrum disorder," Neurology, 2002, 59 (2), 184–192.

[22] V.P. Reinhardt, et al., "Understanding hippocampal development in young children with autism spectrum disorder," J Am Acad Child Adolesc Psychiatry, 2020, 59 (9), 1069–1079.

[23] Q. Xu, C. Zuo, S. Liao, Y. Long, and Y. Wang, "Abnormal development pattern of the amygdala and hippocampus from childhood to adulthood with autism," J Clin Neurosci, 2020, 78, 327–332

DOI: 10.1016/j.jocn.2020.03.049

[24] H. Y. Lin, H. C. Ni, M. C. Lai, W. Y. I. Tseng, and S. S. F. Gau, "Regional brain volume differences between males with and without autism spectrum disorder are highly age-dependent," Mol. Autism, 2015, 6 (1), 1–18.

DOI: 10.1186/s13229-015-0022-3

[25] D. Sussman et al., "The autism puzzle: Diffuse but not pervasive neuroanatomical abnormalities in children with ASD," NeuroImage Clin., 2015, 8, 170–179.

DOI: 10.1016/j.nicl.2015.04.008

[26] A. Y. Hardan, R. R. Girgis, J. Adams, A. R. Gilbert, M. S. Keshavan, and N. J. Minshew, "Abnormal brain size effect on the thalamus in autism," Psychiatry Res. - Neuroimaging, 2006, 147 (2–3), 145–151.

DOI: 10.1016/j.pscychresns.2005.12.009

[27] S. Haar, S. Berman, M. Behrmann, and I. Dinstein, "Anatomical Abnormalities in Autism?," Cereb. Cortex, 2016, 26 (4), 1440–1452.

DOI: 10.1093/cercor/bhu242

[28] N. E. V Foster et al., "Structural gray matter differences during childhood development in autism spectrum disorder: a multimetric approach," Pediatr. Neurol., 2015, 53 (4), 350–359.

DOI: 10.1016/j.pediatrneurol.2015.06.013

[29] M. Langen, S. Durston, W. G. Staal, S. J. M. C. Palmen, and H. van Engeland, "Caudate nucleus is enlarged in high-functioning medication-naive subjects with autism," Biol. Psychiatry, 2007, 62 (3), 262–266.

DOI: 10.1016/j.biopsych.2006.09.040

[30] C. Ecker et al., "Investigating the predictive value of whole-brain structural MR scans in autism: a pattern classification approach," Neuroimage, 2010, 49 (1), 44–56.

DOI: 10.1016/j.neuroimage.2009.08.024

[31] W. Sato et al., "Increased putamen volume in adults with autism spectrum disorder," Front. Hum. Neurosci., 2014, 8, 957.

[32] M. C. Postema et al., "Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets," Nat. Commun., 2019, 10 (1), 1–12.

[33] X. Luo, Q. Mao, J. Shi, X. Wang, and C.-S. R. Li, "Putamen gray matter volumes in neuropsychiatric and neurodegenerative disorders," World J. psychiatry Ment. Heal. Res., 2019, 3 (1).

[34] A. Del Casale, S. Ferracuti, A. Alcibiade, S. Simone, M.N. Modesti, and M. Pompili, "Neuroanatomical correlates of autism spectrum disorders: a meta-analysis of structural magnetic resonance imaging studies," Psychiatry Res Neuroimaging, 2022, 111516

DOI: 10.1016/j.pscychresns.2022.111516

[35] K. Riddle, C.J. Cascio, and N.D. Woodward, "Brain structure in autism: a voxel-based morphometry analysis of the Autism Brain Imaging Database Exchange (ABIDE)," Brain Imaging Behav, 2017, 11, 541–551.

DOI: 10.1007/s11682-016-9534-5

[36] Z.K. Khadem-Reza, and H. Zare, "Evaluation of brain structure abnormalities in children with autism spectrum disorder (ASD) using structural magnetic resonance imaging," Egypt J Neurol Psychiatr Neurosurg, 2022, 58 (1), 1–14.

DOI: 10.1186/s41983-022-00576-5

[37] H. Wang et al. "Developmental brain structural atypicalities in autism: a voxel-based morphometry analysis," Child Adolesc Psychiatry Ment Health, 2022, 16 (1), 1–11.

DOI: 10.1186/s13034-022-00443-4

[38] R.J. Jou, N.J. Minshew, N.M. Melhem, M.S. Keshavan, and A.Y. Hardan, "Brainstem volumetric alterations in children with autism," Psychol Med, 2009, 39 (8), 1347–1354.

DOI: 10.1017/s0033291708004376

[39] R. Tepest, E. Jacobi, A. Gawronski, B. Krug, W. Möller-Hartmann, F.G. Lehnhardt, and K. Vogeley, "Corpus callosum size in adults with high-functioning autism and the relevance of gender," Psychiatry Res Neuroimaging, 2010, 183 (1), 38–43.

DOI: 10.1016/j.pscychresns.2010.04.007

[40] A. Di Martino et al. "The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism," Mol Psychiatry, 2014, 19 (6), 659–667.

[41] M. Jenkinson, C. F. Beckmann, T. E. J. Behrens, M. W. Woolrich, and S. M. Smith. FSL. Neuroimage, 2012, 62 (2), 782–790.

DOI: 10.1016/j.neuroimage.2011.09.015

[42] S.M. Smith et al. "Advances in functional and structural MR image analysis and implementation as FSL," Neuroimage, 2004; 23, S208–19.

[43] K. Kazemi, and N Noori Zadeh. "Quantitative Comparison of SPM, FSL, and Brain suite for Brain MR Image Segmentation." J. of Biomed Physics & Eng, 2014, 4 (1), 13–26.

[44] IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.

[45] V. Arutiunian et al. "Structural brain abnormalities and their association with language impairment in school-aged children with Autism Spectrum Disorder," Sci Rep, 2023, 13 (1), 1172.

DOI: 10.1038/s41598-023-28463-w

[46] M.X. Xu, and X.D. Ju, "Abnormal Brain Structure Is Associated with Social and Communication Deficits in Children with Autism Spectrum Disorder: A Voxel-Based Morphometry Analysis," Brain Sci, 2023, 13 (5), 779

DOI: 10.3390/brainsci13050779