Skip to main content
Log in

Age- and Severity-Specific Deep Learning Models for Autism Spectrum Disorder Classification Using Functional Connectivity Measures

  • Research Article-Electrical Engineering
  • Published:
Arabian Journal for Science and Engineering Aims and scope Submit manuscript

Abstract

Autism spectrum disorder (ASD) is characterized by divergent etiological factors, comorbidities, severity levels, genetic influences, and functional connectivity (FC) patterns in the brain. In the literature, ASD classification based on age and severity using fMRI data is extremely limited. This study explores the impact of age, symptom severity, and brain FC patterns on the diagnosis of ASD using deep neural networks (DNNs). The ability to classify ASD by age and severity using fMRI data is extremely limited. This study explores the impact of age, symptom severity, and brain FC patterns on the diagnosis of ASD using deep neural networks (DNNs). The FC measures were extracted using Pearson's correlation coefficient (PCC), fractal connectivity (FrC), and nonfractal connectivity (NFrC) from the ABIDE I and II databases. We studied three age groups (6 to 11, 11 to 18, and 6 to 18 years) and two severity groups (ADOS score ≤ 11 and ADOS score > 11). The FC matrices are constructed from blood oxygen level-dependent (BOLD) time series signals, and the heat maps are used to generate features for the convolutional neural network (CNN), MobileNetV2, and DenseNet201 models. The MobileNetV2 classifier achieved 76.25% accuracy, 77.09% sensitivity, and 79.77% precision in the age group of 6 to 11 years using NFrC feature maps compared to other DNNs. According to ADOS total scores above 11, DenseNet201 demonstrated superior performance with 83.45% accuracy, 87.3% sensitivity, and 79.13% precision. Connectivity measured by NFrC consistently outperformed Frc measures. Various combinations of connectivity measures and classifiers consistently showed promising results for the age group of 6–11 years and the severity group with an ADOS score of more than 11. ASD's inherent heterogeneity can be addressed effectively by developing diagnostic models tailored to age and severity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Heinsfeld, A.S.; Franco, A.R.; Craddock, R.C.; Buchweitz, A.; Meneguzzi, F.: Identification of autism spectrum disorder using deep learning and the ABIDE dataset. NeuroImage: Clin. 17, 16–23 (2018)

    Google Scholar 

  2. Hull, J.V.; Dokovna, L.B.; Jacokes, Z.J.; Torgerson, C.M.; Irimia, A.; Van Horn, J.D.: GENDAAR research consortium corrigendum: resting-state functional connectivity in autism spectrum disorders: a review. Front. Psych. 9, 268 (2018)

    Google Scholar 

  3. Hashem, S.; Nisar, S.; Bhat, A.A.; Yadav, S.K.; Azeem, M.W.; Bagga, P.; Fakhro, K.; Reddy, R.; Frenneaux, M.P.; Haris, M.: Genetics of structural and functional brain changes in autism spectrum disorder. Transl. Psych. 10(1), 229 (2020)

    Google Scholar 

  4. Solmi, M.; Song, M.; Yon, D.K.; Lee, S.W.; Fombonne, E.; Kim, M.S.; Park, S.; Lee, M.H.; Hwang, J.; Keller, R.; Koyanagi, A.: Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries. Mol. Psych. 29, 1–9 (2022)

    Google Scholar 

  5. Maximo, J.O.; Cadena, E.J.; Kana, R.K.: The implications of brain connectivity in the neuropsychology of autism. Neuropsychol. Rev. 24, 16–31 (2014)

    Google Scholar 

  6. Lombardo, M.V.; Lai, M.C.; Baron-Cohen, S.: Big data approaches to decomposing heterogeneity across the autism spectrum. Mol. Psych. 24(10), 1435–1450 (2019)

    Google Scholar 

  7. Subbaraju, V.; Suresh, M.B.; Sundaram, S.; Narasimhan, S.: Identifying differences in brain activities and an accurate detection of autism spectrum disorder using resting state functional-magnetic resonance imaging: a spatial filtering approach. Med. Image Anal. 35, 375–389 (2017)

    Google Scholar 

  8. Iidaka, T.: Resting state functional magnetic resonance imaging and neural network classified autism and control. Cortex 63, 55–67 (2015)

    Google Scholar 

  9. Plitt, M.; Barnes, K.A.; Martin, A.: Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards. NeuroImage Clin. 7, 359–366 (2015)

    Google Scholar 

  10. Reiter, M.A.; Jahedi, A.; Fredo, A.J.; Fishman, I.; Bailey, B.; Müller, R.A.: Performance of machine learning classification models of autism using resting-state fMRI is contingent on sample heterogeneity. Neural Comput. Appl. 33, 3299–3310 (2021)

    Google Scholar 

  11. Kim, S.; Moon, H.S.; Vo, T.T.; Kim, C.H.; Im, G.H.; Lee, S.; Choi, M.; Kim, S.G.: Whole-brain mapping of effective connectivity by fMRI with cortex-wide patterned optogenetics. Neuron. (2022)

  12. Liégeois, F.; Elward R.: Functional magnetic resonance imaging. InHandbook of clinical neurology 2020 Jan 1 (Vol. 174, pp. 265–275). Elsevier.

  13. Chen, K.; Azeez, A.; Chen, D.Y.; Biswal, B.B.: Resting-state functional connectivity: signal origins and analytic methods. Neuroimag. Clin. 30(1), 15–23 (2020)

    Google Scholar 

  14. Dugré, J.R.; Potvin, S.: Altered functional connectivity of the amygdala across variants of callous-unemotional traits: a resting-state fMRI study in children and adolescents. J. Psych. Res. 2023.

  15. Krishnamurthy, K.; Yeung, M.K.; Chan, A.S.; Han, Y.M.: Effortful control and prefrontal cortex functioning in children with autism spectrum disorder: an fNIRS study. Brain Sci. 10(11), 880 (2020)

    Google Scholar 

  16. Guo, X.; Duan, X.; Chen, H.; He, C.; Xiao, J.; Han, S.; Fan, Y.S.; Guo, J.; Chen, H.: Altered inter-and intrahemispheric functional connectivity dynamics in autistic children. Hum. Brain Mapp. 41(2), 419–428 (2020)

    Google Scholar 

  17. Long, Z.; Duan, X.; Mantini, D., et al.: Alteration of functional connectivity in autism spectrum disorder: effect of age and anatomical distance. Sci. Rep. 6, 26527 (2016). https://doi.org/10.1038/srep26527

    Article  Google Scholar 

  18. Uddin, L.Q.; Supekar, K.; Lynch, C.J., et al.: Salience network-based classification and prediction of symptom severity in children with autism. JAMA Psych. 70(8), 869–879 (2013). https://doi.org/10.1001/jamapsychiatry.2013.104

    Article  Google Scholar 

  19. Supekar, K.; de Los, A.C.; Ryali, S.; Cao, K.; Ma, T.; Menon, V.: Deep learning identifies robust gender differences in functional brain organization and their dissociable links to clinical symptoms in autism. Br. J. Psych. (2022). https://doi.org/10.1192/bjp.2022.13

    Article  Google Scholar 

  20. Liu, X.; Huang, H.: Alterations of functional connectivities associated with autism spectrum disorder symptom severity: a multi-site study using multivariate pattern analysis. Sci. Rep. 10, 4330 (2020). https://doi.org/10.1038/s41598-020-60702-2

    Article  Google Scholar 

  21. Ko, C.; Lim, J.; Hong, J.; Hong, S.; Park, Y.R.: Development and validation of a joint attention-based deep learning system for detection and symptom severity assessment of autism spectrum disorder. JAMA Netw. Open 6(5), e2315174 (2023). https://doi.org/10.1001/jamanetworkopen.2023.15174

    Article  Google Scholar 

  22. Chaitra; Vijaya, P.A.: Machine learning based comparison of Pearson’s and partial correlation measures to quantify functional connectivity in the human brain. IJNBS 6(3), 23–30 (2018)

    Google Scholar 

  23. Wee, C.Y.; Yang, S.; Yap, P.T.; Shen, D.: Alzheimer’s disease neuroimaging Initiative. Sparse temporally dynamic resting-state functional connectivity networks for early MCI identification. Brain Imag. Behav. 10, 342–356 (2016)

    Google Scholar 

  24. Berto, S.; Treacher, A.H.; Caglayan, E.; Luo, D.; Haney, J.R.; Gandal, M.J.; Geschwind, D.H.; Montillo, A.A.; Konopka, G.: Association between resting-state functional brain connectivity and gene expression is altered in autism spectrum disorder. Nat. Commun. 13(1), 3328 (2022)

    Google Scholar 

  25. Sun, C.; Yang, F.; Wang, C.; Wang, Z.; Zhang, Y.; Ming, D.; Du, J.: Mutual information-based brain network analysis in post-stroke patients with different levels of depression. Front. Hum. Neurosci. 12, 285 (2018)

    Google Scholar 

  26. Ronicko, J.F.; Thomas, J.; Thangavel, P.; Koneru, V.; Langs, G.; Dauwels, J.: Diagnostic classification of autism using resting-state fMRI data improves with full correlation functional brain connectivity compared to partial correlation. J. Neurosci. Methods 345, 108884 (2020)

    Google Scholar 

  27. Mohanty, R.; Sethares, W.A.; Nair, V.A.; Prabhakaran, V.: Rethinking measures of functional connectivity via feature extraction. Sci. Rep. 10(1), 1298 (2020)

    Google Scholar 

  28. You, W.; Achard, S.; Stadler, J.; Brückner, B.; Seiffert, U.; Fractal analysis of resting state functional connectivity of the brain. In The 2012 International Joint Conference on Neural Networks (IJCNN) 2012 Jun 10 (pp. 1–8). IEEE.

  29. Dona, O.; Hall, G.B.; Noseworthy, M.D.: Temporal fractal analysis of the rs-BOLD signal identifies brain abnormalities in autism spectrum disorder. PLoS ONE 12(12), e0190081 (2017)

    Google Scholar 

  30. Campbell, O.; Vanderwal, T.; Weber, A.M.: Fractal-based analysis of fMRI BOLD signal during naturalistic viewing conditions. Front. Physiol. 12, 2465 (2022)

    Google Scholar 

  31. Campbell, O.L.; Weber, A.M.: Monofractal analysis of functional magnetic resonance imaging: an introductory review. Hum. Brain Mapp. 43(8), 2693–2706 (2022)

    Google Scholar 

  32. Ochab, J.K.; Wątorek, M.; Ceglarek, A.; Fafrowicz, M.; Lewandowska, K.; Marek, T.; Sikora-Wachowicz, B.; Oświęcimka, P.: Task-dependent fractal patterns of information processing in working memory. Sci. Rep. 1, 17866 (2022)

    Google Scholar 

  33. Sadiq, A.; Yahya, N.; Tang, T.B.; Hashim, H.; Naseem, I.: Wavelet-based fractal analysis of rs-fMRI for classification of alzheimer’s disease. Sensors 22(9), 3102 (2022)

    Google Scholar 

  34. Sadiq, A.; Al-Hiyali, M.I.; Yahya, N.; Tang, T.B.; Khan, D.M.: Non-oscillatory connectivity approach for classification of autism spectrum disorder subtypes using resting-state fMRI. IEEE Access 10, 14049–14061 (2022)

    Google Scholar 

  35. Liu, Y.; Xu, L.; Li, J.; Yu, J.; Yu, X.: Attentional connectivity-based prediction of autism using heterogeneous rs-fMRI data from CC200 atlas. Exp. Neurobiol. 29(1), 27–37 (2020). https://doi.org/10.5607/en.2020.29.1.27

    Article  Google Scholar 

  36. Taban Eslami and Fahad Saeed. 2019. Auto-ASD-Network: A Technique Based on Deep Learning and Support Vector Machines for Diagnosing Autism Spectrum Disorder using fMRI Data. In Proceedings of the 10th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics (BCB '19). Association for Computing Machinery, New York, NY, USA, 646–651. https://doi.org/10.1145/3307339.3343482

  37. Qureshi, M.S.; Qureshi, M.B.; Asghar, J.; Alam, F.; Aljarbouh, A.: Prediction and analysis of autism spectrum disorder using machine learning techniques. J. Healthcare Eng. 4853800, 10 (2023). https://doi.org/10.1155/2023/4853800

    Article  Google Scholar 

  38. Parlett-Pelleriti, C.M.; Stevens, E.; Dixon, D., et al.: Applications of unsupervised machine learning in autism spectrum disorder research: a review. Rev. J. Autism Dev. Disord. 10, 406–421 (2023). https://doi.org/10.1007/s40489-021-00299-y

    Article  Google Scholar 

  39. Eslami, T.; Mirjalili, V.; Fong, A.; Laird, A.R.; Saeed, F.: ASD-DiagNet: a hybrid learning approach for detection of autism spectrum disorder using fMRI data. Front. Neuroinform. 13, 70 (2019)

    Google Scholar 

  40. Byeon, K.; Kwon, J.; Hong, J.; Park, H.: Artificial neural network inspired by neuroimaging connectivity: application in autism spectrum disorder. In2020 IEEE International Conference on Big Data and Smart Computing (BigComp) 2020 Feb 19 (pp. 575–578). IEEE

  41. Dvornek, N.C.; Ventola, P.; Pelphrey, K.A.; Duncan, J.S.: Identifying autism from resting-state fMRI using long short-term memory networks. InMachine Learning in Medical Imaging: 8th International Workshop, MLMI 2017, Held in Conjunction with MICCAI 2017, Quebec City, QC, Canada, September 10, 2017, Proceedings 8 2017 (pp. 362–370). Springer International Publishing.

  42. Bayram, M.A.; İlyas, Ö.Z.; Temurtaş, F.: Deep learning methods for autism spectrum disorder diagnosis based on fMRI images. Sakarya Univ. J. Comput. Inf. Sci. 4(1), 142–155 (2021)

    Google Scholar 

  43. Niu, K.; Guo, J.; Pan, Y.; Gao, X.; Peng, X.; Li, N.; Li, H.: Multichannel deep attention neural networks for the classification of autism spectrum disorder using neuroimaging and personal characteristic data. Complexity 2020, 1–9 (2020)

    Google Scholar 

  44. Leming, M.; Górriz, J.M.; Suckling, J.: Ensemble deep learning on large, mixed-site fMRI datasets in autism and other tasks. Int. J. Neural Syst. 30(07), 2050012 (2020)

    Google Scholar 

  45. Wen, G.; Cao, P.; Bao, H.; Yang, W.; Zheng, T.; Zaiane, O.: MVS-GCN: A prior brain structure learning-guided multi-view graph convolution network for autism spectrum disorder diagnosis. Comput. Biol. Med. 142, 105239 (2022)

    Google Scholar 

  46. Jiang, H.; Cao, P.; Xu, M.; Yang, J.; Zaiane, O.: Hi-GCN: A hierarchical graph convolution network for graph embedding learning of brain network and brain disorders prediction. Comput. Biol. Med. 127, 104096 (2020)

    Google Scholar 

  47. Hiremath, Y.; Ismail, M.; Verma, R.; Antunes, J.; Tiwari, P.: Combining deep and hand-crafted MRI features for identifying sex-specific differences in autism spectrum disorder versus controls. InMedical Imaging 2020: Computer-Aided Diagnosis 2020 Mar 16 (Vol. 11314, pp. 445–451). SPIE.

  48. Al-Hiyali, M.I.; Yahya, N.; Faye, I.; Khan, Z.: Autism spectrum disorder detection based on wavelet transform of bold FMRI signals using pre-trained convolution neural network. Int. J. Int. Eng. 13(5), 49–56 (2021)

    Google Scholar 

  49. Ahammed, M.S.; Niu, S.; Ahmed, M.R.; Dong, J.; Gao, X.; Chen, Y.: Darkasdnet: Classification of ASD on functional MRI using deep neural network. Front. Neuroinform. 15, 635657 (2021)

    Google Scholar 

  50. 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.: The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Mol. Psych. 19(6), 659–667 (2014)

    Google Scholar 

  51. Nair, S.; Jao Keehn, R.J.; Berkebile, M.M.; Maximo, J.O.; Witkowska, N.; Müller, R.A.: Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status. Brain Imag. Behav. 12(1), 168–179 (2018)

    Google Scholar 

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

    Google Scholar 

  53. Cox, R.W.: AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput. Biomed. Res. 29(3), 162–173 (1996)

    Google Scholar 

  54. Jenkinson, M.; Beckmann, C.F.; Behrens, T.E.; Woolrich, M.W.; Smith, S.M.: Fsl. Neuroimage. 62(2), 782–790 (2012)

    Google Scholar 

  55. Teipel, S.J.; Wohlert, A.; Metzger, C.; Grimmer, T.; Sorg, C.; Ewers, M.; Meisenzahl, E.; Klöppel, S.; Borchardt, V.; Grothe, M.J.; Walter, M.: Multicenter stability of resting state FMRI in the detection of Alzheimer’s disease and amnestic MCI. NeuroImage Clin. 14, 183–194 (2017)

    Google Scholar 

  56. Kubanek, D.; Freeborn, T.; Koton, J.; Herencsar, N.: Evaluation of (1+ α) fractional-order approximated Butterworth high-pass and band-pass filter transfer functions. Elektronika ir Elektrotechnika. 24(2), 37–41 (2018)

    Google Scholar 

  57. 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.: 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 (2013)

    Google Scholar 

  58. Gordon, E.M.; Laumann, T.O.; Adeyemo, B.; Huckins, J.F.; Kelley, W.M.; Petersen, S.E.: Generation and evaluation of a cortical area parcellation from resting-state correlations. Cereb. Cortex 26(1), 288–303 (2016)

    Google Scholar 

  59. Desikan, R.S.; Ségonne, F.; Fischl, B.; Quinn, B.T.; Dickerson, B.C.; Blacker, D.; Buckner, R.L.; Dale, A.M.; Maguire, R.P.; Hyman, B.T.; Albert, M.S.: An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31(3), 968–980 (2006)

    Google Scholar 

  60. Diedrichsen, J.; Balsters, J.H.; Flavell, J.; Cussans, E.; Ramnani, N.: A probabilistic MR atlas of the human cerebellum. Neuroimage 46(1), 39–46 (2009)

    Google Scholar 

  61. Nair, A.; Carper, R.A.; Abbott, A.E.; Chen, C.P.; Solders, S.; Nakutin, S.; Datko, M.C.; Fishman, I.; Müller, R.A.: Regional specificity of aberrant thalamocortical connectivity in autism. Hum. Brain Mapp. 36(11), 4497–4511 (2015)

    Google Scholar 

  62. Reiter, M.A.; Mash, L.E.; Linke, A.C.; Fong, C.H.; Fishman, I.; Müller, R.A.: Distinct patterns of atypical functional connectivity in lower-functioning autism. Biol Psych. Cogn. Neurosci. Neuroimag. 4(3), 251–259 (2019)

    Google Scholar 

  63. Kotu, V.; Deshpande, B.: Data science: concepts and practice. Morgan Kaufmann; 2018 Nov 27.

  64. Song, C.; Havlin, S.; Makse, H.A.: Origins of fractality in the growth of complex networks. Nat. Phys. 2(4), 275–281 (2006)

    Google Scholar 

  65. Achard, S.; Bassett, D.S.; Meyer-Lindenberg, A.; Bullmore, E.: Fractal connectivity of long-memory networks. Phys. Rev. E 77(3), 036104 (2008)

    Google Scholar 

  66. Baillie, R.T.; Kapetanios, G.: On the estimation of short memory components in long memory time series models. Stud. Nonlinear Dyn. Econom. 20(4), 365–375 (2016)

    MathSciNet  Google Scholar 

  67. Pradhan, A.; Srivastava, S.: Hierarchical extreme puzzle learning machine-based emotion recognition using multimodal physiological signals. Biomed. Signal Process. Control 83, 104624 (2023)

    Google Scholar 

  68. Kazeminejad, A.; Sotero, R.C.: Topological properties of resting-state fMRI functional networks improve machine learning-based autism classification. Front. Neurosci. 12, 1018 (2019)

    Google Scholar 

  69. Haghighat, H.; Mirzarezaee, M.; Araabi, B.N.; Khadem, A.: An age-dependent Connectivity-based computer aided diagnosis system for autism spectrum disorder using resting-state fMRI. Biomed. Signal Process. Control 71, 103108 (2022)

    Google Scholar 

  70. Vigneshwaran, S.; Suresh, S.; Mahanand, B.S.; Sundararajan, N.: ASD detection in males using MRI-an age-group based study. In2015 International Joint Conference on Neural Networks (IJCNN) 2015 Jul 12 (pp. 1–8). IEEE.

  71. Haweel, R.; Dekhil, O.; Shalaby, A.; Mahmoud, A.; Ghazal, M.; Keynton, R.; Barnes, G.; El-Baz, A.: A machine learning approach for grading autism severity levels using task-based functional MRI. In2019 IEEE International Conference on Imaging Systems and Techniques (IST) 2019 Dec 9 (pp. 1–5). IEEE.

  72. Haweel, R.; Shalaby, A.M.; Mahmoud, A.H.; Ghazal, M.; Seada, N.; Ghoniemy, S.; Casanova, M.; Barnes, G.N.; El-Baz, A.: A novel grading system for autism severity level using task-based functional MRI: a response to speech study. IEEE Access 9, 100570–100582 (2021)

    Google Scholar 

  73. Nomi, J.S.; Uddin, L.Q.: Developmental changes in large-scale network connectivity in autism. NeuroImage Clin. 7, 32–41 (2015)

    Google Scholar 

Download references

Funding

This work was supported by the Science and Engineering Research Board through the Start-up Research Grant (SRG) scheme (SRG/2021/002289).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Murugappan.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jain, V., Rakshe, C.T., Sengar, S.S. et al. Age- and Severity-Specific Deep Learning Models for Autism Spectrum Disorder Classification Using Functional Connectivity Measures. Arab J Sci Eng 49, 6847–6865 (2024). https://doi.org/10.1007/s13369-023-08560-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13369-023-08560-8

Keywords

Navigation