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Front. Integr. Neurosci. | doi: 10.3389/fnint.2019.00010

White Matter Connectome Correlates of Auditory Over-Responsivity: Edge Density Imaging and Machine-learning Classifiers

  • 1School of Medicine, Yale University, United States
  • 2University of California, San Francisco, United States
  • 3University of Washington, United States
  • 4University of Pittsburgh Medical Center, United States
  • 5University of Reading, United Kingdom
  • 6New York University, United States

Sensory over-responsivity (SOR) commonly involves auditory and/or tactile domains, and can affect children with or without additional neurodevelopmental challenges. In this study, we examined white matter microstructural and connectome correlates of auditory over-responsivity (AOR), analyzing prospectively collected data from 39 boys, aged 8-to-12 years. In addition to conventional diffusion tensor imaging (DTI) maps – including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD); we used DTI and high-resolution T1 scans to develop connectome Edge Density (ED) maps. The tract-based spatial statistics was used for voxel-wise comparison of diffusion and ED maps. Then, stepwise penalized logistic regression was applied to identify independent variable(s) predicting AOR, as potential imaging biomarker(s) for AOR. Finally, we compared different combination of machine learning algorithms (i.e. naïve Bayes, random forest, and support vector machine (SVM)) and tract-based DTI/connectome metrics for classification of children with AOR. In direct sensory phenotype assessment, 15 (out of 39) boys exhibited AOR (with or without neurodevelopmental concerns). Voxel-wise analysis demonstrates extensive impairment of white matter microstructural integrity in children with AOR on DTI maps – evidenced by lower FA and higher MD and RD; moreover, there was lower connectome ED in anterior-superior corona radiata, genu and body of corpus callosum. In stepwise logistic regression, the average FA of left superior longitudinal fasciculus (SLF) was the single independent variable distinguishing children with AOR (p=0.007). Subsequently, the left SLF average FA yielded an area under the curve of 0.756 in receiver operating characteristic analysis for prediction of AOR (p= 0.008) as a region-of-interest (ROI)-based imaging biomarker. In comparative study of different combinations of machine-learning models and DTI/ED metrics, random forest algorithms using ED had higher accuracy for AOR classification. Our results demonstrate extensive white matter microstructural impairment in children with AOR, with specifically lower connectomic ED in anterior-superior tracts and associated commissural pathways. Also, average FA of left SLF can be applied as ROI-based imaging biomarker for prediction of SOR. Finally, machine-learning models can provide accurate and objective image-based classifiers for identification of children with AOR based on white matter tracts connectome ED.

Keywords: machine learning, Edge density, Diffusion tensor image (DTI), sensory over responsivity, auditory over resoponsivity, sensory processing disorder

Received: 17 Sep 2018; Accepted: 13 Mar 2019.

Edited by:

Elizabeth B. Torres, Rutgers University, The State University of New Jersey, United States

Reviewed by:

Luis Lemus, National Autonomous University of Mexico, Mexico
Zheng Wang, University of Chinese Academy of Sciences (UCAS), China  

Copyright: © 2019 Payabvash, Palacios, Owen, Wang, Tavassoli, Gerdes, Brandes-Aitken, Mukherjee and Marco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Elysa J. Marco, University of California, San Francisco, San Francisco, 94143, California, United States,