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Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI. Fil: Mitra, Anish. Washington University School Of Medicine In St. Louis; Estados Unidos Fil: Snyder, Abraham Z.. Washington University School Of Medicine In St. Louis; Estados Unidos Fil: Tagliazucchi, Enzo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Laufs, Helmut. Christian-albrechts-universitat Zu Kiel; Alemania Fil: Elison, Jed. University of Minnesota; Estados Unidos Fil: Emerson, Robert W.. University of North Carolina; Estados Unidos Fil: Shen, Mark D.. University of North Carolina; Estados Unidos Fil: Wolff, Jason J.. University of Minnesota; Estados Unidos Fil: Botteron, Kelly N.. Washington University School Of Medicine In St. Louis; Estados Unidos Fil: Dager, Stephen. University Of Washington, Seattle; Estados Unidos Fil: Estes, Annette M.. University Of Washington, Seattle; Estados Unidos Fil: Evans, A.C.. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Gerig, Guido. University of New York; Estados Unidos Fil: Hazlett, Heather C.. University of North Carolina; Estados Unidos Fil: Paterson, Sarah J.. University of Pennsylvania; Estados Unidos Fil: Schultz, Robert T.. University of Pennsylvania; Estados Unidos Fil: Styner, Martin A.. University of North Carolina; Estados Unidos Fil: Zwaigenbaum, Lonnie. University of Alberta; Canadá Fil: Chappell, C.. Ibis Network Pi; Estados Unidos Fil: Estes, A.. University Of Washington, Seattle; Estados Unidos Fil: Shaw, D.. University Of Washington, Seattle; Estados Unidos Fil: Botteron, K.. University Of Washington, Seattle; Estados Unidos Fil: McKinstry, R.. University Of Washington, Seattle; Estados Unidos Fil: Constantino, J.. University Of Washington, Seattle; Estados Unidos Fil: Pruett, J.. University Of Washington, Seattle; Estados Unidos Fil: Schultz, R.. The Children?s Hospital Of Philadelphia; Estados Unidos Fil: Paterson, S.. The Children?s Hospital Of Philadelphia; Estados Unidos Fil: Collins, D.L.. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Pike, G.B.. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Fonov, V.. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Kostopoulos, P.. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Dasso, Sergio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Styner, M.. The University Of North Carolina System; Estados Unidos Fil: Gu, H.. Statistical Analysis Core; Estados Unidos Fil: Schlaggar, Bradley L.. Washington University School Of Medicine In St. Louis; Estados Unidos Fil: Piven, Joseph. University of North Carolina; Estados Unidos Fil: Pruett, John R.. Washington University School Of Medicine In St. Louis; Estados Unidos Fil: Raichle, Marcus. Washington University School Of Medicine In St. Louis; Estados Unidos

Background We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. Methods A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. Results Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. Conclusions This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

BACKGROUND AND PURPOSE: Wallerian degeneration, the secondary degeneration of axons from cortical and subcortical injury, is associated with poor neurologic outcome. Since diffusion-weighted (DW) imaging is sensitive to early changes of cytotoxic edema, DW imaging may depict the acute injury to descending white matter tracts that precedes Wallerian degeneration; this injury is not visible on conventional CT or MR images in the maturing human brain. METHODS: Two neuroradiologists retrospectively analyzed clinical MR images in six children (aged 3 days to 5 months) with DW findings consistent with acute injury of the descending white matter tract due to territorial anterior or middle cerebral artery infarction. In five patients, images were obtained as a part of routine clinical evaluation. The remaining patient was a part of a prospective study of brain injury. Imaging findings were correlated with clinical outcomes. RESULTS: In all six patients, DW imaging performed 2–8 days after the onset of ischemia depicted injury to the descending white matter tract ipsilateral to the territorial infarct. Conventional MR images of the ipsilateral descending white matter tracts were abnormal in three patients. In all five patients for which follow-up results were available, the presence of DW changes was correlated with persistent neurologic disability. CONCLUSION: As shown in this retrospective analysis, DW imaging can depict acute injury to the descending white matter tract in neonates and infants, when conventional MR imaging may show normal findings. These DW findings likely precede the development of Wallerian degeneration, and they may portend a poor clinical outcome.

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low- and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca's area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli.