. 2025 Apr 28;17(1):23.

doi: 10.1186/s11689-025-09613-9.

Functional connectivity between the visual and salience networks and autistic social features at school-age

Jessica B Girault^{1

2}, Tomoyuki Nishino³, Muhamed Talović³, Mary Beth Nebel⁴, Margaret Reynolds⁵, Catherine A Burrows⁶, Jed T Elison⁷, Chimei M Lee⁶, Abraham Z Snyder⁸, Mark D Shen^{9

10}, Audrey M Shen¹¹, Kelly N Botteron^{3

8}, Annette M Estes¹², Stephen R Dager¹³, Guido Gerig¹⁴, Heather C Hazlett^{9

10}, Natasha Marrus³, Robert C McKinstry⁸, Juhi Pandey¹⁵, Robert T Schultz¹⁵, Tanya St John¹², Martin A Styner^{10

16}, Lonnie Zwaigenbaum¹⁷, Alexandre A Todorov^#³, Joseph Piven^#^{9

10}, John R Pruett Jr^#³; IBIS Network

Collaborators, Affiliations

Collaborators

IBIS Network:
J Parish-Morris, B Tunç, W Guthrie, J J Wolff, M R Swanson, H C Hazlett, R Grzadzinski, T St John, D W W Shaw, J N Constantino, A Rocca, C Chappell, A C Evans, L C MacIntyre, S Torres-Gomez, S Das, K Truong, H Volk, S S Jeste, K E MacDuffie

Affiliations

¹ Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Campus Box #3367, Chapel Hill, NC, USA. jessica_girault@med.unc.edu.
² Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jessica_girault@med.unc.edu.
³ Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
⁴ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, USA.
⁵ Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁷ Institute of Child Development, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
⁹ Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Campus Box #3367, Chapel Hill, NC, USA.
¹⁰ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ Easter Seals, UCP, Raleigh, NC, USA.
¹² Department of Speech and Hearing Science, University of Washington, Seattle, WA, USA.
¹³ Department of Radiology, University of Washington Medical Center, Seattle, WA, USA.
¹⁴ Tandon School of Engineering, New York University, New York, NY, USA.
¹⁵ Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁶ Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁷ Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

^# Contributed equally.

PMID: 40295911
PMCID: PMC12036130
DOI: 10.1186/s11689-025-09613-9

Functional connectivity between the visual and salience networks and autistic social features at school-age

Jessica B Girault et al. J Neurodev Disord. 2025.

. 2025 Apr 28;17(1):23.

doi: 10.1186/s11689-025-09613-9.

Authors

Collaborators

IBIS Network:
J Parish-Morris, B Tunç, W Guthrie, J J Wolff, M R Swanson, H C Hazlett, R Grzadzinski, T St John, D W W Shaw, J N Constantino, A Rocca, C Chappell, A C Evans, L C MacIntyre, S Torres-Gomez, S Das, K Truong, H Volk, S S Jeste, K E MacDuffie

Affiliations

¹ Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Campus Box #3367, Chapel Hill, NC, USA. jessica_girault@med.unc.edu.
² Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jessica_girault@med.unc.edu.
³ Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
⁴ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, USA.
⁵ Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁷ Institute of Child Development, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
⁹ Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Campus Box #3367, Chapel Hill, NC, USA.
¹⁰ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ Easter Seals, UCP, Raleigh, NC, USA.
¹² Department of Speech and Hearing Science, University of Washington, Seattle, WA, USA.
¹³ Department of Radiology, University of Washington Medical Center, Seattle, WA, USA.
¹⁴ Tandon School of Engineering, New York University, New York, NY, USA.
¹⁵ Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁶ Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁷ Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.

^# Contributed equally.

PMID: 40295911
PMCID: PMC12036130
DOI: 10.1186/s11689-025-09613-9

Abstract

Background: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD.

Methods: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was used to screen for associations between network-level functional connectivity and six behaviors of interest in a data-driven manner: social affect, restricted and repetitive behavior (RRB), generalized anxiety, inattention, motor coordination, and matrix reasoning.

Results: Functional connectivity between the visual and salience networks was significantly associated with social affect symptoms at school-age after accounting for all other behaviors. Results indicated that stronger connectivity was associated with higher social affect scores. No other behaviors were robustly associated with functional connectivity, though trends were observed between visual-salience connectivity and RRBs.

Conclusions: Connectivity between the visual and salience networks may play an important role in social affect symptom variability among children with ASD and those with genetic liability for ASD. These findings align with and extend earlier reports in this sample of the central role of the visual system during infancy in ASD.

Keywords: Autism; Brain networks; Functional connectivity; MRI; Social behavior.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Informed consent was provided by all participating families. Study procedures were approved by the Institutional Review Boards (IRB) at each research site: University of North Carolina at Chapel Hill, Washington University in St. Louis, University of Washington in Seattle, and the Children’s Hospital of Philadelphia. A single governing IRB at UNC Chapel Hill was in place (IRB #17–1871, PI: Piven). Consent for publication: Not applicable. Competing interests: Dr. Robert McKinstry serves on the medical advisory board and receives stock options for Turing Medical; he also receives funding for meals and travel from Siemens Healthineers, Philips Healthcare, RadiAction Medical, and meals from Hyperfine, Inc. Abraham Z. Snyder is a consultant for Sora Neuroscience, LLC. A.M. Shen discloses a familial relationship with M.D. Shen, but their institution’s COI Office has determined there is no scientific or financial conflict of interest. All other authors report no financial relationships with commercial interests.

Figures

**Fig. 1**
Salience-Visual Functional Connectivity is Associated with Social Affect Scores. ORA results demonstrated a clear shift toward positive values for t-statistics relating fc in SAL-VIS ROI-pairs (red shaded area) to ADOS social affect (SA) scores when compared to the corresponding statistics (grey shaded area) for all other ROI pairs and null t distribution (black line). Results are presented for the entire sample. Analysis based on 250 K permutations of the data

**Fig. 2**
Visualization of Salience-Visual Screening Statistics for Social Affect Scores in Brain Space. Matrix depicts enrichment analysis screening statistics across networks (left panel). Upper triangle displays a heatmap of t-statistics assessing associations between functional connectivity (fc) values and social affect (SA) scores for reach ROI pair (dot in matrix), organized by network: Vis = visual, DMN = default mode network, SMD = somatomotor dorsal, SML = somatomotor lateral, AUD = auditory, DAN = dorsal attention network, VAN = ventral attention network, PMN = parietomedial network, FP = frontoparietal, CO = cingulo-opercular, MTL = medial temporal lobe, REWARD = reward network, SAL = salience. ROIs within each network-network block are organized such that subcortical and cerebellar ROIs are presented first, followed by cortical ROIs. The top left block of the matrix depicts brain-behavior associations in the SAL-VIS network, demonstrating that the vast majority of the positive t-stats (red) are within cortical-cortical ROI pairs. Lower triangles are thresholded to display the strongest brain-behavior associations (top 2.5% of positive and negative t-statistics, or “hits”), colored by whether the t-statistic is positive (red) or negative (blue). The bottom right block of the matrix (green) shows that the vast majority of hits within SAL-VIS are positive, indicating that stronger fc between ROIs in SAL-VIS is associated with higher levels of SA impairment. Visualization of top hits in brain space (right panel)

**Fig. 3**
GSEA Profiles Depict Specific Brain-Behavior Associations Unique to the Salience-Visual Network Pair. GSEA profiles (a) when screening with partial F statistics for association between fc and SA and/or RRB. There is clustering of large F values in the SAL-VIS network pair (red curve and tick marks); blue curves represent profiles for other network pairs, truncated at 0 for clarity. Smaller network pairs exhibit some instability in the profile. Only the SAL-VIS finding is statistically significant. b Profiles when screening SAL-VIS ROI-pairs with t-statistics, one per variable. Clustering of larger t statistics is found for SAL-VIS and SA (p = 0.00056), with trend-level findings for RRB (p = 0.00072), but not for the other variables (see Table 2). Results presented for the entire sample

See this image and copyright information in PMC

References

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Functional connectivity between the visual and salience networks and autistic social features at school-age

Collaborators

Affiliations

Functional connectivity between the visual and salience networks and autistic social features at school-age

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical