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Background <p>fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD.</p> Methods <p>fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, <i>N</i> = 23) and ASD-negative (HLN, <i>N</i> = 91), and low-likelihood ASD-negative (LLN, <i>N</i> = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses.</p> Results <p>OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (<i>p</i> = 0.012), but none for HLP versus HLN (<i>p</i> = 0.047) nor HLN versus LLN (<i>p</i> = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)– temporal default mode network (tDMN) pair (<i>p</i> = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (<i>p</i> = 0.0461 and 0.0004). HLP did not differ from HLN (<i>p</i> = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (<i>p</i> = 0.0036).</p> Conclusions <p>24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.</p>

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Brain functional connectivity correlates of autism diagnosis and familial liability in 24-month-olds

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  • 发表日期：

    2025年7月18日

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  • John R Pruett Jr.,
  • Alexandre A Todorov,
  • Zoë W Hawks,
  • Muhamed Talovic,
  • Tomoyuki Nishino,
  • Steven E Petersen,
  • Savannah Davis,
  • Lyn Stahl,
  • Kelly N Botteron,
  • John N Constantino,
  • Stephen R Dager,
  • Jed T Elison,
  • Annette M Estes,
  • Alan C Evans,
  • Guido Gerig,
  • Jessica B Girault,
  • Heather Hazlett,
  • Leigh MacIntyre,
  • Natasha Marrus,
  • Robert C McKinstry,
  • Juhi Pandey,
  • Robert T Schultz,
  • William D Shannon,
  • Mark D Shen,
  • Abraham Z Snyder,
  • Martin Styner,
  • Jason J Wolff,
  • Lonnie Zwaigenbaum,
  • Joseph Piven,
  • J. Piven,
  • J.R. Pruett,
  • R.T. Schultz,
  • J. Pandey,
  • J. Parish-Morris,
  • B. Tunc,
  • W. Guthrie,
  • J.T. Elison,
  • J.J. Wolff,
  • C.A. Burrows,
  • H.C. Hazlett,
  • M.D. Shen,
  • J.B. Girault,
  • R. Grzadzinski,
  • S.R. Dager,
  • A.M. Estes,
  • T. St. John,
  • D.W.W. Shaw,
  • K.N. Botteron,
  • R.C. McKinstry,
  • J.N. Constantino,
  • N. Marrus,
  • A. Rocca,
  • C. Chappell,
  • L. Zwaigenbaum,
  • M.R. Swanson,
  • M.A. Styner,
  • G. Gerig,
  • A.C. Evans,
  • L.C. MacIntyre,
  • S. Torres-Gomez,
  • S. Das,
  • K. Truong,
  • H. Volk,
  • M.D. Fallin,
  • S.S. Jeste,
  • K.E. MacDuffie

摘要

Background

fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD.

Methods

fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses.

Results

OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)– temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036).

Conclusions

24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.