Association of Sleep Spindle Rate With Memory Consolidation in Children With Rolandic Epilepsy

Overview

Journal Neurology

Date 2025 Jan 13

PMID 39804468

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: Rolandic epilepsy (RE), the most common childhood focal epilepsy syndrome, is characterized by a transient period of sleep-activated epileptiform activity in the centrotemporal regions and variable cognitive deficits. 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 RE and related sleep-activated epileptic encephalopathies. To further evaluate the association between this electrographic biomarker and cognitive dysfunction in this common disease, we investigate whether children with RE have deficient sleep-dependent memory consolidation and whether impaired memory consolidation is associated with reduced sleep spindles in the centrotemporal regions.

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 an automated sleep spindle detector validated for use in children with and without epilepsy.

Results: Twenty-three children with RE (9 with active disease, 5F, age 6.9-12.8 years; 14 with resolved disease, 8F, age 8.8-17.8 years) and 19 age-matched and sex-matched controls (8F, age 6.9-18.7 years) were enrolled. Children with active epilepsy had decreased memory consolidation compared with control children ( = 0.001, mean percentage reduction 25.7%, 95% CI 10.3%-41.2%) and compared with children with resolved epilepsy ( = 0.007, mean percentage reduction 21.9%, 95% CI 6.2%-37.6%). Children with active epilepsy had decreased sleep spindle rates in the centrotemporal region compared with controls ( = 0.008, mean decrease 2.5 spindles per minute, 95% CI 0.7-4.4 spindles per minute). Spindle rate, but not spike rate or spike-wave index, correlated with sleep-dependent memory consolidation ( = 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 RE have impaired sleep-dependent memory consolidation during the active period of disease that correlates with a deficit in the sleep spindle rate. This finding identifies a noninvasive biomarker to aid diagnosis and a potential etiologic mechanism to guide therapeutic discovery of cognitive dysfunction in RE and related sleep-activated epilepsy syndromes.

Citing Articles

Mechanistic insights into the interaction between epilepsy and sleep.

Sheybani L, Frauscher B, Bernard C, Walker M Nat Rev Neurol. 2025; .

PMID: 40065066 DOI: 10.1038/s41582-025-01064-z.

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

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

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

Kwon H, Chinappen D, Huang J, Berja E, Walsh K, Shi W . Transient, developmental functional and structural connectivity abnormalities in the thalamocortical motor network in Rolandic epilepsy. Neuroimage Clin. 2022; 35:103102. PMC: 9251597. DOI: 10.1016/j.nicl.2022.103102. 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

Tovia E, Goldberg-Stern H, Ben Zeev B, Heyman E, Watemberg N, Fattal-Valevski A . The prevalence of atypical presentations and comorbidities of benign childhood epilepsy with centrotemporal spikes. Epilepsia. 2011; 52(8):1483-8. DOI: 10.1111/j.1528-1167.2011.03136.x. 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.

Spencer E, Chinappen D, Emerton B, Morgan A, Hamalainen M, Manoach D . Source EEG reveals that Rolandic epilepsy is a regional epileptic encephalopathy. Neuroimage Clin. 2022; 33:102956. PMC: 8844714. DOI: 10.1016/j.nicl.2022.102956. View

12.

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

13.

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

14.

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

15.

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

16.

Wodeyar A, Chinappen D, Mylonas D, Baxter B, Manoach D, Eden U . Thalamic epileptic spikes disrupt sleep spindles in patients with epileptic encephalopathy. Brain. 2024; 147(8):2803-2816. PMC: 11492493. DOI: 10.1093/brain/awae119. 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.

Warby S, Wendt S, Welinder P, Munk E, Carrillo O, Sorensen H . Sleep-spindle detection: crowdsourcing and evaluating performance of experts, non-experts and automated methods. Nat Methods. 2014; 11(4):385-92. PMC: 3972193. DOI: 10.1038/nmeth.2855. View

20.

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