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Peer-reviewedCC BYBiological Psychiatry Cognitive Neuroscience and Neuroimaging

Altered Sensorimotor-Association Axis Patterning of Global Functional Connectivity in an Autism Subtype With Low Levels of Language, Intellectual, and Adaptive Functioning

  • Ines Severino1
  • Veronica Mandelli2
  • Natasha Bertelsen2
  • Michael Vincent Lombardo3
  1. 1Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy; Center for Mind/Brain Sciences, University of Trento, Rovereto, Italy
  2. 2Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy
  3. 3Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy. Electronic address: [email protected]
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Abstract

BACKGROUND: During early development, autism can be stratified into subtypes differentiated by non-core language, intellectual, motor, and adaptive functioning features. During toddlerhood, these subtypes show different genomic patterning effects on brain structure and function that follow early primary axes of neurodevelopmental organization. This leads to the hypothesis that early cortical patterning differences may continue to be evident between subtypes in later development within hierarchical organization along the sensorimotor-association (S-A) axis. METHODS: Standardized phenotypic measures from the National Institute of Mental Health Data Archive (n = 419) were used in unsupervised data-driven clustering analyses to build a phenotypic stratification model based on language, intellectual, and adaptive functioning (LIAF) features. This stratification model was then applied to independent multi-site resting-state functional magnetic resonance imaging datasets (autism n = 174; typically developing [TD] n = 185) to test for subtype differences in global functional connectivity. Mass univariate and multivariate patterning analyses were used to test for differences between TD and autism subtypes. RESULTS: Clustering revealed 2 phenotypically distinct autism subtypes (high vs. low) in late childhood to adulthood that generalized in independent data with 92% accuracy. Autism was associated with hyper-connectivity in association areas alongside hypo-connectivity in sensorimotor areas. However, these differences were most pronounced in the TD versus autism low LIAF group comparison and resembled patterning effects that follow the SA axis. CONCLUSIONS: These findings suggest that cortical patterning of global functional connectivity along the S-A axis is different in autistic children compared with TD children and may be relatively more pronounced in autism with low LIAF features.

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Cite

BibTeXRIS
BibTeX
@article{severino2026altered,
  title = {{Altered Sensorimotor-Association Axis Patterning of Global Functional Connectivity in an Autism Subtype With Low Levels of Language, Intellectual, and Adaptive Functioning}},
  author = {Ines Severino and Veronica Mandelli and Natasha Bertelsen and Michael Vincent Lombardo},
  journal = {Biological Psychiatry Cognitive Neuroscience and Neuroimaging},
  year = {2026},
  month = jun,
  doi = {10.1016/j.bpsc.2026.06.005},
  url = {https://doi.org/10.1016/j.bpsc.2026.06.005},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Altered Sensorimotor-Association Axis Patterning of Global Functional Connectivity in an Autism Subtype With Low Levels of Language, Intellectual, and Adaptive Functioning
AU  - Ines Severino
AU  - Veronica Mandelli
AU  - Natasha Bertelsen
AU  - Michael Vincent Lombardo
PY  - 2026
DA  - 2026/06/01
JO  - Biological Psychiatry Cognitive Neuroscience and Neuroimaging
DO  - 10.1016/j.bpsc.2026.06.005
UR  - https://doi.org/10.1016/j.bpsc.2026.06.005
AB  - BACKGROUND: During early development, autism can be stratified into subtypes differentiated by non-core language, intellectual, motor, and adaptive functioning features. During toddlerhood, these subtypes show different genomic patterning effects on brain structure and function that follow early primary axes of neurodevelopmental organization. This leads to the hypothesis that early cortical patterning differences may continue to be evident between subtypes in later development within hierarchical organization along the sensorimotor-association (S-A) axis. METHODS: Standardized phenotypic measures from the National Institute of Mental Health Data Archive (n = 419) were used in unsupervised data-driven clustering analyses to build a phenotypic stratification model based on language, intellectual, and adaptive functioning (LIAF) features. This stratification model was then applied to independent multi-site resting-state functional magnetic resonance imaging datasets (autism n = 174; typically developing [TD] n = 185) to test for subtype differences in global functional connectivity. Mass univariate and multivariate patterning analyses were used to test for differences between TD and autism subtypes. RESULTS: Clustering revealed 2 phenotypically distinct autism subtypes (high vs. low) in late childhood to adulthood that generalized in independent data with 92% accuracy. Autism was associated with hyper-connectivity in association areas alongside hypo-connectivity in sensorimotor areas. However, these differences were most pronounced in the TD versus autism low LIAF group comparison and resembled patterning effects that follow the SA axis. CONCLUSIONS: These findings suggest that cortical patterning of global functional connectivity along the S-A axis is different in autistic children compared with TD children and may be relatively more pronounced in autism with low LIAF features.
SN  - 2451-9022
SN  - 2451-9030
ER  -