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EEG Spectral Features in Sleep of Autism Spectrum Disorders in Children with Tuberous Sclerosis Complex

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Abstract

Tuberous sclerosis complex (TSC) is a multisystem disorder with increased prevalence of autism spectrum disorders (ASDs). This project aimed to characterize the autism phenotype of TSC and identify biomarkers of risk for ASD. Because abnormalities of EEG during sleep are tied to neurodevelopment in children, we compared electroencephalographic (EEG) measures during Stage II sleep in TSC children who either did (ASD+) or did not (ASD−) exhibit symptoms of ASD over 36-month follow up. Relative alpha band power was significantly elevated in the ASD+ group at 24 months of age with smaller differences at younger ages, suggesting this may arise from differences in brain development. These findings suggest that EEG features could enhance the detection of risk for ASD.

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References

  • American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, DC: American Psychiatric Pub.

    Google Scholar 

  • Armitage, R., Trivedi, M., & Rush, J. A. (1995). Fluoxetine and oculomotor activity during sleep in depressed patients. Neuropsychopharmacology,12(2), 159.

    Article  Google Scholar 

  • Bruni, O., Cortesi, F., Giannotti, F., & Curatolo, P. (1995). Sleep disorders in tuberous sclerosis: A polysomnographic study. Brain and Development,17(1), 52–56.

    Article  Google Scholar 

  • Buchmann, A., Ringli, M., Kurth, S., Schaerer, M., Geiger, A., Jenni, O. G., et al. (2010). EEG sleep slow-wave activity as a mirror of cortical maturation. Cerebral Cortex,21(3), 607–615.

    Article  Google Scholar 

  • Catalano, D., Holloway, L., & Mpofu, E. (2018). Mental health interventions for parent carers of children with autistic spectrum disorder: Practice guidelines from a Critical Interpretive Synthesis (CIS) Systematic Review. International Journal of Environmental Research and Public Health,15(2), 341.

    Article  Google Scholar 

  • Çetin, Ö. E., Korkmaz, B., Alev, G., & Demirbilek, V. (2017). EEG abnormalities and long term seizure outcome in high functioning autism. Acta Neurologica Belgica,117(3), 729–732.

    Article  Google Scholar 

  • Christensen, D. L., Bilder, D. A., Zahorodny, W., Pettygrove, S., Durkin, M. S., Fitzgerald, R. T.,… & Yeargin-Allsopp, M. (2016). Prevalence and characteristics of autism spectrum disorder among 4-year-old children in the autism and developmental disabilities monitoring network. Journal of Developmental & Behavioral Pediatrics, 37(1), 1–8.

  • Cohen, S., Conduit, R., Lockley, S. W., Rajaratnam, S. M., & Cornish, K. M. (2014). The relationship between sleep and behavior in autism spectrum disorder (ASD): A review. Journal of Neurodevelopmental Disorders,6(1), 44.

    Article  Google Scholar 

  • David, N., Schneider, T. R., Peiker, I., Al-Jawahiri, R., Engel, A. K., & Milne, E. (2016). Variability of cortical oscillation patterns: A possible endophenotype in autism spectrum disorders? Neuroscience and Biobehavioral Reviews,71, 590–600.

    Article  Google Scholar 

  • Fernandez, B. A., & Scherer, S. W. (2017). Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach. Dialogues in Clinical Neuroscience,19(4), 353–371.

    PubMed  PubMed Central  Google Scholar 

  • Gabard-Durnam, L. J., Wilkinson, C., Kapur, K., Tager-Flusberg, H., Levin, A. R., & Nelson, C. A. (2019). Longitudinal EEG power in the first postnatal year differentiates autism outcomes. Nature Communications,10(1), 4188.

    Article  Google Scholar 

  • Hens, K., Robeyns, I., & Schaubroeck, K. (2019). The ethics of autism. Philosophy Compass,14, e12559.

    Article  Google Scholar 

  • Hodge, D., Carollo, T. M., Lewin, M., Hoffman, C. D., & Sweeney, D. P. (2014). Sleep patterns in children with and without autism spectrum disorders: Developmental comparisons. Research in Developmental Disabilities,35(7), 1631–1638.

    Article  Google Scholar 

  • Hunt, A. (1993). Development, behaviour and seizures in 300 cases of tuberous sclerosis. Journal of Intellectual Disability Research,37(1), 41–51.

    Article  Google Scholar 

  • Johnson, C. R., Smith, T., DeMand, A., Lecavalier, L., Evans, V., Gurka, M., & Scahill, L. (2018). Exploring sleep quality of young children with autism spectrum disorder and disruptive behaviors. Sleep Medicine, 44, 61–66.

    Article  Google Scholar 

  • Kharoshankaya, L., Murray, D. M., Bogue, C., Ahearne, C., Murphy, B. P., & Boylan, G. B. (2016). Early EEG findings in tuberous sclerosis complex presenting with apneic seizures soon after birth. Clinical Neurophysiology,127(10), 3265–3267.

    Article  Google Scholar 

  • Köse, S., Yilmaz, H., Ocakoğlu, F. T., & Özbaran, N. B. (2017). Sleep problems in children with autism spectrum disorder and intellectual disability without autism spectrum disorder. Sleep Medicine,40, 69–77.

    Article  Google Scholar 

  • Kurth, S., Ringli, M., Geiger, A., LeBourgeois, M., Jenni, O. G., & Huber, R. (2010). Mapping of cortical activity in the first two decades of life: A high-density sleep electroencephalogram study. The Journal of Neuroscience,30(40), 13211–13219.

    Article  Google Scholar 

  • Landa, R. J. (2018). Efficacy of early interventions for infants and young children with, and at risk for, autism spectrum disorders. International Review of Psychiatry,30(1), 25–39.

    Article  Google Scholar 

  • Levin, A. R., Varcin, K. J., O’Leary, H. M., Tager-Flusberg, H., & Nelson, C. A. (2017). EEG power at 3 months in infants at high familial risk for autism. Journal of Neurodevelopmental Disorders.,9(1), 34.

    Article  Google Scholar 

  • Maxwell, C. R., Villalobos, M. E., Schultz, R. T., Herpertz-Dahlmann, B., Konrad, K., & Kohls, G. (2015). Atypical laterality of resting gamma oscillations in autism spectrum disorders. Journal of Autism and Developmental Disorders,45(2), 292–297.

    Article  Google Scholar 

  • Mitchell, R., Barton, S., Harvey, A. S., & Williams, K. (2017). Risk factors for the development of autism spectrum disorder in children with tuberous sclerosis complex: Protocol for a systematic review. Systematic Reviews,6, 49.

    Article  Google Scholar 

  • Modabbernia, A., Velthorst, E., & Reichenberg, A. (2017). Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Molecular Autism,8, 13.

    Article  Google Scholar 

  • Novelli, L., D’atri, A., Marzano, C., Finotti, E., Ferrara, M., Bruni, O., et al. (2016). Mapping changes in cortical activity during sleep in the first 4 years of life. Journal of Sleep Research,25(4), 381–389.

    Article  Google Scholar 

  • Tierney, A. L., Gabard-Durnam, L., Vogel-Farley, V., Tager-Flusberg, H., & Nelson, C. A. (2012). Developmental trajectories of resting EEG power: An endophenotype of autism spectrum disorder. PLoS ONE,7(6), e39127.

    Article  Google Scholar 

  • Trickett, J., Heald, M., Oliver, C., & Richards, C. (2018). A cross-syndrome cohort comparison of sleep disturbance in children with Smith-Magenis syndrome, Angelman syndrome, autism spectrum disorder and tuberous sclerosis complex. Journal of Neurodevelopmental Disorders,10(1), 9.

    Article  Google Scholar 

  • van Diessen, E., Senders, J., Jansen, F. E., Boersma, M., & Bruining, H. (2015). Increased power of resting-state gamma oscillations in autism spectrum disorder detected by routine electroencephalography. European Archives of Psychiatry and Clinical Neuroscience,265(6), 537–540.

    Article  Google Scholar 

  • Verhoeff, M. E., Blanken, L. M. E., Kocevska, D., Mileva-Seitz, V. R., Jaddoe, V. W. V., White, T., et al. (2018). The bidirectional association between sleep problems and autism spectrum disorder: a population-based cohort study. Molecular Autism,9, 8.

    Article  Google Scholar 

  • Yasuhara, A. (2010). Correclation between EEG abnormalities and symptoms of autism spectrum disorder (ASD). Brain and Development,32(10), 791–798.

    Article  Google Scholar 

Download references

Acknowledgments

We are sincerely indebted to the generosity of the families and patients in Tuberculosis Sclerosis Complex (TSC) clinics across the United States who contributed their time and effort to this study. We would also like to thank the Tuberous Sclerosis Alliance for their continued support in TSC research. IC, JP, MG, MB, HN, DK, AL, and MS conceived of the study and participated in its design and coordination. IC and AL drafted the manuscript. All authors performed the measurements. IC, AW, and AL participated in data analysis and the interpretation of the results. All authors read, edited and approved of the final manuscript.

Funding

Funding

Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NINDS) and Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) under Award Number U01NS082320. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, #57-456, Los Angeles, CA, 90024, USA

    Ian A. Cook, Andrew C. Wilson & Andrew F. Leuchter

  2. Department of Psychiatry & Biobehavioral Sciences, UCLA David Geffen School of Medicine, 760 Westwood Plaza, Los Angeles, CA, 90024, USA

    Ian A. Cook & Andrew F. Leuchter

  3. Department of Bioengineering, UCLA Henry Samueli School of Engineering at Applied Science, 760 Westwood Plaza, Los Angeles, CA, 90024, USA

    Ian A. Cook

  4. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA

    Jurriaan M. Peters

  5. Department of Neurology, University of Alabama at Birmingham, 1600 7th Avenue S, Birmingham, AL, 35233, USA

    Monisha N. Goyal & E. Martina Bebin

  6. Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, 1941 East Road, 3.126 BBSB, Houston, TX, 77054, USA

    Hope Northrup

  7. Department of Neurology and Rehabilitation Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7004, Cincinnati, OH, 45229, USA

    Darcy Krueger

  8. Department of Neurology, Harvard Medical School, Harvard University, 300 Longwood Avenue, Boston, MA, 02115, USA

    Mustafa Sahin

  9. Boston Children’s Hospital, F.M. Kirby Neurobiology Center, 300 Longwood Avenue, Boston, MA, 02115, USA

    Mustafa Sahin

Authors
  1. Ian A. Cook
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  2. Andrew C. Wilson
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  4. Monisha N. Goyal
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  5. E. Martina Bebin
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  6. Hope Northrup
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  7. Darcy Krueger
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  8. Andrew F. Leuchter
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  9. Mustafa Sahin
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the TACERN Study Group

Corresponding author

Correspondence to Andrew F. Leuchter.

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Conflict of interest

Dr. Cook discloses that he has received research support from Covidien (formerly Aspect Medical Systems), National Institutes of Health, and NeoSync, Inc. within the past 3 years; he has been an advisor/consultant/reviewer for Arctica Health, Cerêve, HeartCloud, NeuroDetect, NeuroSigma, NIH (ITVA), U.S. Departments of Defense and Justice, and the VA (DSMB); he is editor of the Patient Management section of the American Psychiatric Association’s FOCUS journal; his biomedical intellectual property is assigned to the Regents of the University of California, and he has stock options in NeuroSigma, where he has served as Chief Medical Officer (on leave); he is employed by the University of California, Los Angeles and also has an appointment as a Staff Psychiatrist, Neuromodulation and Mood Disorders programs, Greater Los Angeles Veterans Administration Health System. Dr. Peters has received consulting fees from Philips Neuro. Dr. Bebin has received research support from the National Institute of Health. She has served on the Board of Directors for the Tuberous Sclerosis Alliance. Dr. Krueger has received research grants from the National Institute of Neurological Disorders and Stroke, Tuberous Sclerosis Alliance, and Novartis Pharmaceuticals. She has received honoraria from Norvartis Pharmaceuticals. She is on the advisory boards for Novartis Pharmaceuticals and Upsher-Smith Pharmaceuticals. Dr. Leuchter discloses that within the past 36 months he has received research support from the National Institutes of Health, Neuronetics, Department of Defense, CHDI Foundation, and NeuroSigma, Inc. He has served as a consultant to NeoSync, Inc., Ionis Pharmaceuticals, Inc., and ElMindA. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). Dr. Leuchter owns stock options in NeoSync, Inc. and has equity interest in BBA. Dr. Sahin has received grant support from Novartis Pharmaceuticals, Roche, Pfizer, Ipsen and LAM Therapeutics and Quandrant Biosciences. He has served on scientific advisory boards for Sage, Roche, and Takeda. Mr. Wilson, Dr. Goyal, Dr. Northrup declare no conflicts of interests.

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Cook, I.A., Wilson, A.C., Peters, J.M. et al. EEG Spectral Features in Sleep of Autism Spectrum Disorders in Children with Tuberous Sclerosis Complex. J Autism Dev Disord 50, 916–923 (2020). https://doi.org/10.1007/s10803-019-04326-0

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