Poster No:
434
Submission Type:
Abstract Submission
Authors:
Emily Chiem1, Lauren Wagner1, Kate de Guillenchmidt1, Mirella Dapretto1
Institutions:
1UCLA, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
Sleep disruption is pervasive in autism spectrum disorder (ASD) (1) and one of the first concerns raised by parents before diagnosis (2). While proper sleep is critical for neurodevelopment, it is unclear how sleep problems may impact brain development in infancy and later developmental outcomes. Studying infant siblings of autistic children can offer insights into the relationship between sleep and neurodevelopment because 20% of infant siblings will receive a diagnosis (3). Thalamocortical connectivity plays an important role in mediating sleep states (4) and is altered in infants with a family history of ASD (5-6) as well as in older autistic individuals where it has been associated with both sleep (7) and sensory sensitivities (8). In this study, we examined how early thalamocortical connectivity might relate to sleep-onset problems in 6-month-old infants at high familial likelihood for ASD.
Methods:
Data were collected as part of the Infant Brain Imaging Study (R01HD055741). Infants with an older sibling with ASD were deemed high likelihood (HL), while those with no first or second-degree relatives with ASD were deemed typical likelihood (TL). Resting-state fMRI scans were collected during natural sleep at 6 months of age (N=60). Scans were preprocessed and analyzed using FSL, including linear registration to an infant brain template (10), spatial smoothing, motion correction using ICA-AROMA, bandpass filtering, and CSF, white matter, and global signal regression. Five items from the Infant Behavior Questionnaire were used to create an Infant Sleep-Onset Problems (ISOP) score. Between-group comparisons were conducted using left and right thalamus seeds, masked by joint group-level functional connectivity maps. Similar connectivity patterns were observed from both seeds; thus, the bilateral thalamus was used in subsequent analyses (Z > 2.3, cluster-corrected at P < 0.05). Due to limited variability in ISOP scores in TL infants, parameter estimates of global thalamic connectivity were correlated with ISOP scores only for HL infants. A region-of-interest (ROI) analysis in HL infants correlated ISOP scores with connectivity between thalamus and bilateral somatosensory cortices.
Results:
HL infants had weaker thalamic connectivity with the right orbitofrontal cortex and left cerebellum compared to TL infants. Additionally, in HL infants, stronger thalamic connectivity with both cortical and subcortical regions related to higher ISOP scores (P=0.05). Subsequent ROI analysis showed that thalamic connectivity with bilateral somatosensory cortex was positively correlated with ISOP scores in HL infants (P=0.03).
Conclusions:
Our finding that HL infants displayed thalamic hypoconnectivity with right orbitofrontal cortex is consistent with prior reports of weaker thalamic connectivity with right prefrontal cortex in 1.5-month-old HL infants (5), indicating a stable pattern of thalamic-prefrontal underconnectivity in HL infants across the first 6 months of life. Similarly, our finding of weaker thalamic-cerebellar connectivity in HL infants shows that the underconnectivity between thalamus and cerebellum previously observed in 9-month-old HL infants (10) is already present at 6 months of age. We also found that worse sleep-onset problems in HL infants were associated with heightened thalamic connectivity with both cortical and subcortical regions, suggesting a link between global thalamic overconnectivity and longer sleep latencies. Our result that stronger thalamic connectivity with somatosensory cortices is associated with worse sleep-onset problems in HL infants is line with previous evidence that thalamic hyperconnectivity with the somatosensory cortex is also associated with sensory over-responsivity (6). Altogether, these results revealed consistent atypicalities in thalamic connectivity in HL infants in the first 9 months of life and indicated a relationship between altered thalamocortical connectivity and sleep-onset problems in HL infants.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Perception, Attention and Motor Behavior:
Sleep and Wakefulness 2
Keywords:
Autism
Cortex
FUNCTIONAL MRI
PEDIATRIC
Sleep
Thalamus
1|2Indicates the priority used for review
Provide references using author date format
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