The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence
- 250 Downloads
During the course of adolescence, reductions occur in cortical thickness and gray matter (GM) volume, along with a 65% reduction in slow-wave (delta) activity during sleep (SWA) but empirical data linking these structural brain and functional sleep differences, is lacking. Here, we investigated specifically whether age-related differences in cortical thickness and GM volume and cortical thickness accounted for the typical age-related difference in slow-wave (delta) activity (SWA) during sleep. 132 healthy participants (age 12–21 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study were included in this cross-sectional analysis of baseline polysomnographic, electroencephalographic, and magnetic resonance imaging data. By applying mediation models, we identified a large, direct effect of age on SWA in adolescents, which explained 45% of the variance in ultra-SWA (0.3–1 Hz) and 52% of the variance in delta-SWA (1 to <4 Hz), where SWA was lower in older adolescents, as has been reported previously. In addition, we provide evidence that the structure of several, predominantly frontal, and parietal brain regions, partially mediated this direct age effect, models including measures of brain structure explained an additional 3–9% of the variance in ultra-SWA and 4–5% of the variance in delta-SWA, with no differences between sexes. Replacing age with pubertal status in models produced similar results. As reductions in GM volume and cortical thickness likely indicate synaptic pruning and myelination, these results suggest that diminished SWA in older, more mature adolescents may largely be driven by such processes within a number of frontal and parietal brain regions.
KeywordsSlow-wave activity Adolescence Cortical development Sleep
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank our lab manager, Stephanie Claudatos, and research assistants, David Dresser, David Sugarbaker, Justin Greco, Sarah Inkelis, Lena Kardos, Devika Nair, and Leonardo Rosas, for their effort in collecting data for this project, and all research participants.
Compliance with ethical standards
Conflict of interest
FCB and MdZ have received research grants from Fitbit Inc., Ebb Inc., and International Flavors and Fragrances Inc.
This study was supported by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA); grants: AA021690 (DBC), AA021697 (AP + KMP), AA021697-04S1 (KMP), AA021696 (IMC + FCB) and AA021695 (NCANDA Admin).
- Baker FC, Willoughby AR, de Zambotti M, Franzen PL, Prouty D, Javitz H, Hasler B, Clark DB, Colrain IM (2016) Age-related differences in sleep architecture and electroencephalogram in adolescents in the national consortium on alcohol and neurodevelopment in adolescence sample. Sleep 39(7):1429–1439. doi: 10.5665/sleep.5978 PubMedPubMedCentralCrossRefGoogle Scholar
- Bramen JE, Hranilovich JA, Dahl RE, Forbes EE, Chen J, Toga AW, Dinov ID, Worthman CM, Sowell ER (2011) Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity. Cereb Cortex 21(3):636–646. doi: 10.1093/cercor/bhq137 PubMedCrossRefGoogle Scholar
- Bramen JE, Hranilovich JA, Dahl RE, Chen J, Rosso C, Forbes EE, Dinov ID, Worthman CM, Sowell ER (2012) Sex matters during adolescence: testosterone-related cortical thickness maturation differs between boys and girls. PLoS One 7(3):e33850. doi: 10.1371/journal.pone.0033850 PubMedPubMedCentralCrossRefGoogle Scholar
- Brown SA, Brumback T, Tomlinson K, Cummins K, Thompson WK, Nagel BJ, De Bellis MD, Hooper SR, Clark DB, Chung T, Hasler BP, Colrain IM, Baker FC, Prouty D, Pfefferbaum A, Sullivan EV, Pohl KM, Rohlfing T, Nichols BN, Chu W, Tapert SF (2015) The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): a multisite study of adolescent development and substance use. J Stud Alcohol Drugs 76(6):895–908PubMedPubMedCentralCrossRefGoogle Scholar
- Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger JI Jr, Reich T, Schmidt I, Schuckit MA (1994) A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. J Stud Alcohol 55(2):149–158PubMedCrossRefGoogle Scholar
- Dang-Vu TT, Schabus M, Desseilles M, Albouy G, Boly M, Darsaud A, Gais S, Rauchs G, Sterpenich V, Vandewalle G, Carrier J, Moonen G, Balteau E, Degueldre C, Luxen A, Phillips C, Maquet P (2008) Spontaneous neural activity during human slow wave sleep. Proc Natl Acad Sci USA 105(39):15160–15165. doi: 10.1073/pnas.0801819105 PubMedPubMedCentralCrossRefGoogle Scholar
- Desikan RS, Segonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, Buckner RL, Dale AM, Maguire RP, Hyman BT, Albert MS, Killiany RJ (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31(3):968–980. doi: 10.1016/j.neuroimage.2006.01.021 PubMedCrossRefGoogle Scholar
- Feinberg I, Higgins LM, Khaw WY, Campbell IG (2006) The adolescent decline of NREM delta, an indicator of brain maturation, is linked to age and sex but not to pubertal stage. Am J Physiol Regul Integr Comp Physiol 291(6):R1724–R1729. doi: 10.1152/ajpregu.00293.2006 PubMedPubMedCentralCrossRefGoogle Scholar
- Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF 3rd, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 101(21):8174–8179. doi: 10.1073/pnas.0402680101 PubMedPubMedCentralCrossRefGoogle Scholar
- Hayes AF (2013) Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. Guilford Press, New YorkGoogle Scholar
- Kennedy C, Sokoloff L (1957) An adaptation of the nitrous oxide method to the study of the cerebral circulation in children; normal values for cerebral blood flow and cerebral metabolic rate in childhood. J Clin Investig 36(7):1130–1137. doi: 10.1172/jci103509 PubMedPubMedCentralCrossRefGoogle Scholar
- Lopes da Silva FH, van Rotterdam A (2005) Biophysical aspects of EEG and magnetoencephalographic generation. In: Niedermeyer E, Lopes da Silva F (eds) Electroencephalography: basic principles, clinical applications and related fields, 5th edn. Lippincott, Williams & Wilkins, New YorkGoogle Scholar
- Lopes da Silva FH (2010) EEG: origin and measurement. In: Mulert C, Lemieux L (eds) EEG-fMRI: physiological basis, technique, and applications. Springer, Berlin, Heidelberg, pp 19–38Google Scholar
- Mills KL, Goddings A-L, Herting MM, Meuwese R, Blakemore S-J, Crone EA, Dahl RE, Güroğlu B, Raznahan A, Sowell ER, Tamnes CK (2016) Structural brain development between childhood and adulthood: convergence across four longitudinal samples. Neuroimage 141:273–281. doi: 10.1016/j.neuroimage.2016.07.044 PubMedPubMedCentralCrossRefGoogle Scholar
- Moroni F, Nobili L, Iaria G, Sartori I, Marzano C, Tempesta D, Proserpio P, Lo Russo G, Gozzo F, Cipolli C, De Gennaro L, Ferrara M (2014) Hippocampal slow EEG frequencies during NREM sleep are involved in spatial memory consolidation in humans. Hippocampus 24(10):1157–1168. doi: 10.1002/hipo.22299 PubMedCrossRefGoogle Scholar
- Pfefferbaum A, Rohlfing T, Pohl KM, Lane B, Chu W, Kwon D, Nolan Nichols B, Brown SA, Tapert SF, Cummins K, Thompson WK, Brumback T, Meloy MJ, Jernigan TL, Dale A, Colrain IM, Baker FC, Prouty D, De Bellis MD, Voyvodic JT, Clark DB, Luna B, Chung T, Nagel BJ, Sullivan EV (2015) Adolescent development of cortical and white matter structure in the NCANDA sample: role of sex, ethnicity, puberty, and alcohol drinking. Cereb Cortex. doi: 10.1093/cercor/bhv205 Google Scholar
- Pohl KM, Sullivan EV, Rohlfing T, Chu W, Kwon D, Nichols BN, Zhang Y, Brown SA, Tapert SF, Cummins K, Thompson WK, Brumback T, Colrain IM, Baker FC, Prouty D, De Bellis MD, Voyvodic JT, Clark DB, Schirda C, Nagel BJ, Pfefferbaum A (2016) Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study. Neuroimage 130:194–213. doi: 10.1016/j.neuroimage.2016.01.061 PubMedPubMedCentralCrossRefGoogle Scholar
- Steriade M, McCarley R (2005) Brain control of wakefulness and sleeping. Springer, New YorkGoogle Scholar
- Sullivan EV, Pfefferbaum A, Rohlfing T, Baker FC, Padilla ML, Colrain IM (2011) Developmental change in regional brain structure over 7 months in early adolescence: comparison of approaches for longitudinal atlas-based parcellation. Neuroimage 57(1):214–224. doi: 10.1016/j.neuroimage.2011.04.003 PubMedPubMedCentralCrossRefGoogle Scholar
- Sullivan EV, Brumback T, Tapert SF, Fama R, Prouty D, Brown SA, Cummins K, Thompson WK, Colrain IM, Baker FC, De Bellis MD, Hooper SR, Clark DB, Chung T, Nagel BJ, Nichols BN, Rohlfing T, Chu W, Pohl KM, Pfefferbaum A (2016) Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction. Neuropsychology 30(4):449–473. doi: 10.1037/neu0000259 PubMedPubMedCentralCrossRefGoogle Scholar
- Whitaker KJ, Vertes PE, Romero-Garcia R, Vasa F, Moutoussis M, Prabhu G, Weiskopf N, Callaghan MF, Wagstyl K, Rittman T, Tait R, Ooi C, Suckling J, Inkster B, Fonagy P, Dolan RJ, Jones PB, Goodyer IM, Bullmore ET (2016) Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome. Proc Natl Acad Sci USA 113(32):9105–9110. doi: 10.1073/pnas.1601745113 PubMedPubMedCentralCrossRefGoogle Scholar