@article{afe92d4403934f759f2fe38a2146259b,
title = "Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex",
abstract = "Objective: To identify whether abnormal electroencephalography (EEG) connectivity is present before the onset of epileptic spasms (ES) in infants with tuberous sclerosis complex (TSC). Methods: Scalp EEG recordings were collected prospectively in infants diagnosed with TSC in the first year of life. This study compared the earliest recorded EEG from infants prior to ES onset (n = 16) and from infants who did not develop ES (n = 28). Five minutes of stage II or quiet sleep was clipped and filtered into canonical EEG frequency bands. Mutual information values between each pair of EEG channels were compared directly and used as a weighted graph to calculate graph measures of global efficiency, characteristic path length, average clustering coefficient, and modularity. Results: At the group level, infants who later developed ES had increased EEG connectivity in sleep. They had higher mutual information values between most EEG channels in all frequency bands adjusted for age. Infants who later developed ES had higher global efficiency and average clustering coefficients, shorter characteristic path lengths, and lower modularity across most frequency bands adjusted for age. This suggests that infants who went on to develop ES had increased local and long-range EEG connectivity with less segregation of graph regions into distinct modules. Significance: This study suggests that increased neural connectivity precedes clinical ES onset in a cohort of infants with TSC. Overconnectivity may reflect progressive pathologic network synchronization culminating in generalized ES. Further research is needed before scalp EEG connectivity measures can be used as a potential biomarker of ES risk and treatment response in pre-symptomatic infants with TSC.",
keywords = "functional connectivity, graph theory, infantile spasms, mutual information",
author = "{on behalf of the Tuberous Sclerosis Autism Centers of Excellence Research Network} and Davis, {Peter E.} and Kush Kapur and Rajna Filip-Dhima and Trowbridge, {Sara K.} and Elaina Little and Andrew Wilson and Andrew Leuchter and Bebin, {Elizabeth M.} and Darcy Krueger and Hope Northrup and Wu, {Joyce Y.} and Mustafa Sahin and Peters, {Jurriaan M.} and S. Warfield and J. Peters and M. Goyal and K. Dies and S. Bruns and E. Hanson and N. Bing and B. Kent and S. O'Kelley and M. William and D. Pearson and D. Murray and G. Cutter and S. Roberds and B. Scherrer",
note = "Funding Information: Research reported in this publication was supported by the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) under Award Numbers U01NS082320 and P20NS080199. Peter E. Davis is supported by the Neurology Resident Research Education Program from the NIH NINDS (5R25NS070682‐07), the Boston Children's Funding Information: E. Martina Bebin serves on the scientific advisory board for Novartis Pharmaceuticals and GW Pharma and receives clinical research support from Novartis Pharmaceuticals and GW Pharma. Joyce Y. Wu serves on the professional advisory board for the Tuberous Sclerosis Alliance; has received honoraria from and serves on the scientific advisory board and the speakers{\textquoteright} bureau for Novartis Pharmaceuticals Inc. and Lundbeck; and has received research support from the Tuberous Sclerosis Alliance, Novartis Pharmaceuticals Inc., and Today and Tomorrow Children's Fund. Mustafa Sahin has received research funding from Roche, Novartis, Pfizer, LAM Therapeutics, and Quadrant Biosciences and has served on the Scientific Advisory Board of Sage Therapeutics, Roche, Takeda, and PTEN Research Foundation. In addition, he serves on the Professional Advisory Board of the Tuberous Sclerosis Alliance. Darcy Krueger has received research funding from Novartis, Clack Foundation, and the Tuberous Sclerosis Alliance. In addition, he has received consultant fees from Novartis and serves on the Professional Advisory Board of the Tuberous Sclerosis Alliance. Andrew Wilson has served as a consultant to HeartCloud, Inc. The remaining authors have no conflict of interests. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Funding Information: Funding information Research reported in this publication was supported by the?National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) under Award Numbers U01NS082320 and P20NS080199. Peter E. Davis is supported by the Neurology Resident Research Education Program from the NIH NINDS (5R25NS070682-07), the Boston Children's Hospital Office of Faculty Development, and the Tuberous Sclerosis Alliance. Joyce Y. Wu is supported by the UCLA CTRC funded by the NIH grant UL1TR0000124. Peter E. Davis, E. Martina Bebin, Joyce Y. Wu, Darcy Krueger, and Mustafa Sahin are supported by the Developmental Synaptopathies Consortium (U54-NS092090), part of the National Center for Advancing Translational Sciences Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research, NCATS, funded through collaboration between NCATS, the National Institute of Mental Health, NINDS, and NICHD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We are sincerely indebted to the generosity of the families and patients in 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 of TSC research. Funding Information: E. Martina Bebin receives NIH funding from U01‐NS082320, P20‐NS080199, and U01‐NS092595. Joyce Y. Wu receives research funding from the Department of Defense/ Congressionally Directed Medical Research Program and the NIH (P20‐NS080199, U01‐NS082320, R01‐NS082649, and U01‐NS092595). Darcy Krueger has received research funding from the NIH (U01‐NS082320, U01‐NS092595). Mustafa Sahin has received research funding from the NIH (U01‐NS082320, U01‐NS092595, U54HD090255) and Department of Defense W81XWH‐15‐1‐0189. Other than the items listed under Potential Conflicts of Interest, the authors have no financial relationships relevant to this article to disclose. Funding Information: Hospital Office of Faculty Development, and the Tuberous Sclerosis Alliance. Joyce Y. Wu is supported by the UCLA CTRC funded by the NIH grant UL1TR0000124. Peter E. Davis, E. Martina Bebin, Joyce Y. Wu, Darcy Krueger, and Mustafa Sahin are supported by the Developmental Synaptopathies Consortium (U54‐ NS092090), part of the National Center for Advancing Translational Sciences Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research, NCATS, funded through collaboration between NCATS, the National Institute of Mental Health, NINDS, and NICHD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: Wiley Periodicals, Inc. {\textcopyright} 2019 International League Against Epilepsy",
year = "2019",
doi = "10.1111/epi.16284",
language = "English (US)",
volume = "60",
pages = "1721--1732",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "8",
}