Amanda R. Halliday ¹ Samuel N. Vucic ¹ Brianna Georges ¹ Madison LaRoche ¹ María A. Mendoza Pardo ¹ Liam O. Swiggard ¹ Kaylee McDonald ¹ Michelle Olofsson ^1,2 Sahit Menon ^3,4 S M. Francis ⁴ Lindsay M. Oberman ⁴ Tonya White ¹ Isabelle Van Der Velpen ^1*

• ¹ Section on Social and Cognitive Developmental Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, Illinois, United States
• ² Department of Clinical Neuroscience, Karolinska Institutet (KI), Stockholm, Stockholm, Sweden
• ³ University of California, San Diego, School of Medicine, La Jolla, United States
• ⁴ Noninvasive Neuromodulation Unit, Experimental Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States

Background: A growing body of literature classifies autism spectrum disorder (ASD) as a heterogeneous, complex neurodevelopmental disorder that often is identified prior to three years of age. We aim to provide a narrative review of key structural and functional properties that differentiate the neuroimaging profile of autistic youth from their typically developing (TD) peers across different neuroimaging modalities.Methods: Relevant studies were identified by searching for key terms in PubMed, with the most recent search conducted on September 1, 2023. Original research papers were included if they applied at least one of seven neuroimaging modalities (structural MRI, functional MRI, DTI, MRS, fNIRS, MEG, EEG) to compare autistic children or those with a family history of ASD to TD youth or those without ASD family history; included only participants <18 years; and were published from 2013 to 2023.In total, 172 papers were considered for qualitative synthesis. When comparing ASD to TD groups, structural MRI-based papers (n = 26) indicated larger subcortical gray matter volume in ASD groups. DTI-based papers (n = 14) reported higher mean and radial diffusivity in ASD participants. Functional MRI-based papers (n = 41) reported a substantial number of between-network functional connectivity findings in both directions. MRS-based papers (n = 19) demonstrated higher metabolite markers of excitatory neurotransmission and lower inhibitory markers in ASD groups. fNIRS-based papers (n = 20) reported lower oxygenated hemoglobin signals in ASD. Converging findings in MEG-(n = 20) and EEG-based (n = 32) papers indicated lower event-related potential and field amplitudes in ASD groups. Findings in the anterior cingulate cortex, insula, prefrontal cortex, amygdala, thalamus, cerebellum, corpus callosum, and default mode network appeared numerous times across modalities and provided opportunities for multimodal qualitative analysis.Comparing across neuroimaging modalities, we found significant differences between the ASD and TD neuroimaging profile in addition to substantial heterogeneity. Inconsistent results are frequently seen within imaging modalities, comparable study populations and research designs. Still, converging patterns across imaging modalities support various existing theories on ASD.