Sleep Problems in Preschoolers With Autism Spectrum Disorder Are Associated With Sensory Sensitivities and Thalamocortical Overconnectivity

Abstract

Background: Projections between the thalamus and sensory cortices are established early in development and play an important role in regulating sleep as well as in relaying sensory information to the cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorder (ASD) might therefore be linked to sensory and sleep problems common in ASD.

Methods: Here, we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep functional magnetic resonance imaging, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5-5 years old) with ASD compared with a matched group of 46 typically developing children.

Results: In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high-quality magnetic resonance imaging data (n = 29). In addition, auditory cortex blood oxygen level-dependent signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep.

Conclusions: These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.

Keywords: Autism spectrum disorder; Functional connectivity; Sensory processing; Sleep; Thalamus.

Figure 1.

Greater sleep problems and sensory sensitivity, including auditory sensitivity, in toddlers and preschoolers with autism spectrum disorder (ASD). (A, C) More severe sleep problems (as measured using the Child Behavior Checklist [CBCL] Sleep Problems scale, T scores) and prolonged sleep latency (time [in min] it takes a child to fall asleep, as reported on an in-house Sleep Questionnaire that asked caregivers about their child’s sleep habits in the past few weeks prior to participating in the study) are reported for young children with ASD compared with age- and sex-matched typically developing (TD) children, in (A) the full cohort and (C) the subgroup of children with successful functional magnetic resonance imaging (fMRI) scans (fMRI cohort). (B, D) Toddlers and preschoolers with ASD show greater sensory sensitivity and more severe auditory processing symptoms, as measured using the Sensory Profile 2 (T scores), in (B) the full cohort and (D) the subgroup of children with successful fMRI scans (fMRI cohort). These results remained significant when controlling for gestational age at birth and socioeconomic status, and no significant effects of sex (or sex × diagnosis interactions) were observed (see the Supplement).

Figure 2.

Correlations between sensory sensitivity, sleep problems, and Heschl’s gyrus (HG)–thalamus functional connectivity (FC). (A, B) The Sensory Profile Sensitivity score correlates positively (partial correlation controlling for age) with sleep problems as quantified using the Child Behavior Checklist (CBCL) Sleep Problems T score in the (A) full and (B) functional magnetic resonance imaging (fMRI)–only autism spectrum disorder groups. This association between sensory sensitivity and sleep problems remained significant when controlling for gestational age or socioeconomic status, with no sex differences observed (see the Supplement). Correlations were not assessed for the typically developing group due to the narrow distribution of scores in typically developing children for these measures. (C) Sleep latency correlates positively (partial correlations controlling for in-scanner head motion [root-mean-square deviation] and age) with contralateral FC between the thalamus and HG in the autism spectrum disorder group. See the Supplement for additional analyses testing the effects of gestational age, socioeconomic status, sex, and sleep stage on HG-thalamus FC. All scatterplots show zero-order correlations. Robust linear regressions as implemented in MATLAB (2017b; The MathWorks, Inc.) with the robustfit function were conducted as post hoc analyses to minimize the potential influence of outliers. The association between the Sensory Profile Sensitivity score and CBCL Sleep Problems T score (controlling for age) remained significant in the full cohort (t = 2.04, p < .05; fMRI cohort t = 1.6, p = .12). Similarly, the relationship between sleep latency and contralateral HG-thalamus FC (controlling for age and root-mean-square deviation) remained significant (t = 2.5, p < .05; ipsilateral FC: t = 1.7, p = .1).

Figure 3.

Thalamic (Thal)–Heschl’s gyrus (HG) overconnectivity in young children with autism spectrum disorder (ASD). (A) Toddlers and preschoolers with ASD show overconnectivity between the thalamus and HG during natural sleep functional magnetic resonance imaging compared with age-, motion-, and sex-matched typically developing (TD) children (* in the ASD matrix mark region of interest [ROI] pairs with significant group differences, p < .05, Benjamini-Hochberg false discovery rate (FDR)–adjusted for multiple comparisons). Functional connectivity was significantly different from zero for HG.R-Thal.L (one-sample t test: t₂₈ = 2.3, p = .03) in the ASD group (but t values for all ROI pairs were positive) and for HG.R-Thal.R (t₂₉ = −2.4, p = .03) in the TD group (with t values for all ROI pairs negative). (B) Ipsilateral and contralateral functional connectivity was similarly elevated in toddlers and preschoolers with ASD and used for behavioral correlations in subsequent analyses. (C) Seed-to-ROI analyses show that thalamocortical overconnectivity is most pronounced for auditory regions. Left (L) and right (R) thalami were used as seeds and all cortical Harvard-Oxford atlas ROIs as targets. t values for the ASD > TD comparison are shown with * marking significant (p < .05, uncorrected) group differences in functional connectivity. (D) Thal-HG overconnectivity in the ASD group appears to be driven by the posterior section of the thalamus. Left and right HG were used as seeds and all voxels in the thalamus as targets.