Dyscoordination of Non-Rapid Eye Movement Sleep Oscillations in Autism Spectrum Disorder

TY - JOUR

T1 - Dyscoordination of Non-Rapid Eye Movement Sleep Oscillations in Autism Spectrum Disorder

AU - Mylonas, Dimitrios

AU - Machado, Sasha

AU - Larson, Olivia

AU - Patel, Rudra

AU - Cox, Roy

AU - Vangel, Mark

AU - Maski, Kiran

AU - Stickgold, Robert

AU - Manoach, Dara S

N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected].

PY - 2022

Y1 - 2022

N2 - STUDY OBJECTIVES: Converging evidence from neuroimaging, sleep, and genetic studies suggests that dysregulation of thalamocortical interactions mediated by the thalamic reticular nucleus (TRN) contribute to autism spectrum disorder (ASD). Sleep spindles assay TRN function, and their coordination with cortical slow oscillations (SOs) indexes thalamocortical communication. These oscillations mediate memory consolidation during sleep. In the present study, we comprehensively characterized spindles and their coordination with SOs in relation to memory and age in children with ASD.METHODS: Nineteen children and adolescents with ASD, without intellectual disability, and 18 typically developing (TD) peers, aged 9-17, completed a home polysomnography study with testing on a spatial memory task before and after sleep. Spindles, SOs, and their coordination were characterized during stages 2 (N2) and 3 (N3) non-rapid eye movement sleep.RESULTS: ASD participants showed disrupted SO-spindle coordination during N2 sleep. Spindles peaked later in SO upstates and their timing was less consistent. They also showed a spindle density (#/min) deficit during N3 sleep. Both groups showed significant sleep-dependent memory consolidation, but its relations with spindle density differed. While TD participants showed the expected positive correlations, ASD participants showed the opposite.CONCLUSIONS: The disrupted SO-spindle coordination and spindle deficit provide further evidence of abnormal thalamocortical interactions and TRN dysfunction in ASD. The inverse relations of spindle density with memory suggest a different function for spindles in ASD than TD. We propose that abnormal sleep oscillations reflect genetically mediated disruptions of TRN-dependent thalamocortical circuit development that contribute to the manifestations of ASD and are potentially treatable.

AB - STUDY OBJECTIVES: Converging evidence from neuroimaging, sleep, and genetic studies suggests that dysregulation of thalamocortical interactions mediated by the thalamic reticular nucleus (TRN) contribute to autism spectrum disorder (ASD). Sleep spindles assay TRN function, and their coordination with cortical slow oscillations (SOs) indexes thalamocortical communication. These oscillations mediate memory consolidation during sleep. In the present study, we comprehensively characterized spindles and their coordination with SOs in relation to memory and age in children with ASD.METHODS: Nineteen children and adolescents with ASD, without intellectual disability, and 18 typically developing (TD) peers, aged 9-17, completed a home polysomnography study with testing on a spatial memory task before and after sleep. Spindles, SOs, and their coordination were characterized during stages 2 (N2) and 3 (N3) non-rapid eye movement sleep.RESULTS: ASD participants showed disrupted SO-spindle coordination during N2 sleep. Spindles peaked later in SO upstates and their timing was less consistent. They also showed a spindle density (#/min) deficit during N3 sleep. Both groups showed significant sleep-dependent memory consolidation, but its relations with spindle density differed. While TD participants showed the expected positive correlations, ASD participants showed the opposite.CONCLUSIONS: The disrupted SO-spindle coordination and spindle deficit provide further evidence of abnormal thalamocortical interactions and TRN dysfunction in ASD. The inverse relations of spindle density with memory suggest a different function for spindles in ASD than TD. We propose that abnormal sleep oscillations reflect genetically mediated disruptions of TRN-dependent thalamocortical circuit development that contribute to the manifestations of ASD and are potentially treatable.

U2 - 10.1093/sleep/zsac010

DO - 10.1093/sleep/zsac010

M3 - Article

C2 - 35022792

SN - 0161-8105

VL - 45

JO - Sleep

JF - Sleep

M1 - zsac010

ER -