Impaired Sleep-dependent Memory Consolidation Predicted by Reduced Sleep Spindles in Rolandic Epilepsy

Overview

Journal bioRxiv

Date 2024 May 27

PMID 38798414

Authors

Hunki Kwon

Dhinakaran M Chinappen

Elizabeth A Kinard

Skyler K Goodman

Jonathan F Huang

Erin D Berja

Katherine G Walsh

Wen Shi

Dara S Manoach

Mark A Kramer

Catherine J Chu

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy.

Methods: In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector.

Results: Twenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute).

Discussion: Children with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.

References

Fernandez L, Luthi A . Sleep Spindles: Mechanisms and Functions. Physiol Rev. 2019; 100(2):805-868. DOI: 10.1152/physrev.00042.2018. View

Kurdziel L, Duclos K, Spencer R . Sleep spindles in midday naps enhance learning in preschool children. Proc Natl Acad Sci U S A. 2013; 110(43):17267-72. PMC: 3808582. DOI: 10.1073/pnas.1306418110. View

Fischer S, Hallschmid M, Elsner A, Born J . Sleep forms memory for finger skills. Proc Natl Acad Sci U S A. 2002; 99(18):11987-91. PMC: 129381. DOI: 10.1073/pnas.182178199. View

Manoach D, Cain M, Vangel M, Khurana A, Goff D, Stickgold R . A failure of sleep-dependent procedural learning in chronic, medicated schizophrenia. Biol Psychiatry. 2004; 56(12):951-6. DOI: 10.1016/j.biopsych.2004.09.012. View

Hahn M, Joechner A, Roell J, Schabus M, Heib D, Gruber G . Developmental changes of sleep spindles and their impact on sleep-dependent memory consolidation and general cognitive abilities: A longitudinal approach. Dev Sci. 2018; 22(1):e12706. PMC: 6492121. DOI: 10.1111/desc.12706. View

Astill R, Piantoni G, Raymann R, Vis J, Coppens J, Walker M . Sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children. Front Hum Neurosci. 2014; 8:910. PMC: 4227520. DOI: 10.3389/fnhum.2014.00910. View

Hoedlmoser K, Heib D, Roell J, Peigneux P, Sadeh A, Gruber G . Slow sleep spindle activity, declarative memory, and general cognitive abilities in children. Sleep. 2014; 37(9):1501-12. PMC: 4153050. DOI: 10.5665/sleep.4000. View

Sirota A, Csicsvari J, Buhl D, Buzsaki G . Communication between neocortex and hippocampus during sleep in rodents. Proc Natl Acad Sci U S A. 2003; 100(4):2065-9. PMC: 149959. DOI: 10.1073/pnas.0437938100. View

Ross E, Stoyell S, Kramer M, Berg A, Chu C . The natural history of seizures and neuropsychiatric symptoms in childhood epilepsy with centrotemporal spikes (CECTS). Epilepsy Behav. 2019; 103(Pt A):106437. PMC: 8087164. DOI: 10.1016/j.yebeh.2019.07.038. View

10.

van Schalkwijk F, Gruber W, Miller L, Trinka E, Holler Y . Investigating the Effects of Seizures on Procedural Memory Performance in Patients with Epilepsy. Brain Sci. 2021; 11(2). PMC: 7922212. DOI: 10.3390/brainsci11020261. View

11.

McLaren J, Luo Y, Kwon H, Shi W, Kramer M, Chu C . Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy. Ann Clin Transl Neurol. 2023; 10(9):1513-1524. PMC: 10502632. DOI: 10.1002/acn3.51840. View

12.

Bender A, Jaleel A, Pellerin K, Moguilner S, Sarkis R, Cash S . Altered Sleep Microarchitecture and Cognitive Impairment in Patients With Temporal Lobe Epilepsy. Neurology. 2023; 101(23):e2376-e2387. PMC: 10752648. DOI: 10.1212/WNL.0000000000207942. View

13.

Wilhelm I, Diekelmann S, Born J . Sleep in children improves memory performance on declarative but not procedural tasks. Learn Mem. 2008; 15(5):373-7. DOI: 10.1101/lm.803708. View

14.

Bouma P, Bovenkerk A, Westendorp R, Brouwer O . The course of benign partial epilepsy of childhood with centrotemporal spikes: a meta-analysis. Neurology. 1997; 48(2):430-7. DOI: 10.1212/wnl.48.2.430. View

15.

Beenhakker M, Huguenard J . Neurons that fire together also conspire together: is normal sleep circuitry hijacked to generate epilepsy?. Neuron. 2009; 62(5):612-32. PMC: 2748990. DOI: 10.1016/j.neuron.2009.05.015. View

16.

Fischl B . FreeSurfer. Neuroimage. 2012; 62(2):774-81. PMC: 3685476. DOI: 10.1016/j.neuroimage.2012.01.021. View

17.

Schiller K, Avigdor T, Abdallah C, Sziklas V, Crane J, Stefani A . Focal epilepsy disrupts spindle structure and function. Sci Rep. 2022; 12(1):11137. PMC: 9249850. DOI: 10.1038/s41598-022-15147-0. View

18.

Merikanto I, Kuula L, Makkonen T, Halonen R, Lahti J, Heinonen K . ADHD symptoms are associated with decreased activity of fast sleep spindles and poorer procedural overnight learning during adolescence. Neurobiol Learn Mem. 2018; 157:106-113. DOI: 10.1016/j.nlm.2018.12.004. View

19.

Kwon H, Walsh K, Berja E, Manoach D, Eden U, Kramer M . Sleep spindles in the healthy brain from birth through 18 years. Sleep. 2023; 46(4). PMC: 10091086. DOI: 10.1093/sleep/zsad017. View

20.

Bruni O, Ferri R, Novelli L, Terribili M, Troianiello M, Finotti E . Sleep spindle activity is correlated with reading abilities in developmental dyslexia. Sleep. 2009; 32(10):1333-40. PMC: 2753811. DOI: 10.1093/sleep/32.10.1333. View