Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

Table 1

(a) Characteristics of sleep spindles and associations between sleep spindles and cognitive function in children with attention deficit hyperactivity disorder (ADHD) versus typically developing children. (b) Characteristics of sleep spindles and associations between sleep spindles and cognitive function in children with autism spectrum disorder (ASD) versus typically developing children. (c) Characteristics of sleep spindles and associations between sleep spindles and cognitive function in children with developmental dyslexia (DD) versus typically developing children. (d) Characteristics of sleep spindles and associations between sleep spindles and cognitive function in children with intellectual disability (ID) versus typically developing children. (e) Characteristics of sleep spindles and associations between sleep spindles and cognitive function in typically developing (TPD) children.

(a)

Reference	Disorder	Cognitive impairment	Age	Sample size	Study design	⁢Sleep measure		Cognitive measure (outcome/s)	⁢Results
						Recording parameters	Spindles scoring		Sleep	Cognition	Sleep and cognition
Kiesow and Surwillo, 1987 [100]	ADHD	None	ADHD patients: Range: 3–11; Mean: 6.69; Controls: Range: 3–11; Mean: 6.69	ADHD patients: 11; Controls: 11; 100% males	Correlational study	10–20 International System of electrode placement	S2 sleep spindles		No significant differences
Prehn-Kristensen et al., 2011 [103]	ADHD	None	ADHD: 12–16; Controls: 11–14	ADHD: 12; Controls: 12	Experimental; Case-control Repeated; Measures; Design	PSG (sampling rate: 200 Hz with 12-bit resolution). EEG (C3, C4, A1, and A2), EOG, and EMG.	Sleep spindles detected using a band-pass filter of 12–14 Hz, of S2 sleep	Declarative memory consolidation task (recognition accuracy)	ADHD participants: more REM sleep and shorter SWS latency	() Overall reduced recognition accuracy in ADHD group.; () Enhanced recognition accuracy in the sleep condition, but greater in control compared to ADHD	Positive association between; () duration of non-REM sleep and; () slow oscillation power and sleep-associated memory consolidation in healthy controls but not in ADHD

(b)

Reference

Disorder

Cognitive impairment

Age

Sample size

Study design

Sleep measure

Cognitive measure (outcome/s)

Results

Recording parameters

Spindles scoring

Sleep

Cognition

Sleep and cognition

Godbout et al.,; 2000 [96]

ASD

None

AS: 7–53; Controls: 7–61

ASD: 8; Controls: 8

Correlational study

PSG

S2 sleep spindles: 12–15 Hz, lasting 0.5–2.0 s, no amplitude criteria

ASD participants: () More transitions from a waking epoch to REM sleep compared to healthy controls.; () Made less transitions from a S2 epoch to REM sleep compared to healthy controls.; () Lower S2 spindle density.

Limoges et al.,; 2005 [108]

ASD

None

ASD: 16–27; Controls: 16–26

ASD: 16; Controls: 16

Correlational study

PSG. EEG (C3, C4, O1, and O2), and EOG, EMG.

S2 sleep spindles (C3, Fp1): 12–15 Hz, lasting 0.5–2.0 s, no amplitude criteria

ASD participants: () Increased time in S1 and decreased non-REM sleep and SWS; () Lower S2 sleep spindle density (C3) compared to healthy controls

Limoges et al.,; 2013 [97]

ASD

None

ASD: 16–27; Controls: 16–27

17 ASD; 14 controls

Correlational study

PSG (C3, C4, O1, and O2), EOG, and EMG.

S2 sleep spindles

Sustained and selective attention (RT); working memory (span score); Declarative episodic memory (# of recalled figures) Sensory-motor procedural memory (contact time, # of trials); Procedural memory (time)

() Lower REM density.; () Lower SWS%; () Higher S1% in lower S2 spindle density (C3) in AS compared to controls

Poorer performance in ASD compared to controls on sustained attention working memory. Sensory-motor procedural memory

() Positive association in controls but not in ASD between the SWS% and declarative memory immediate recall; () Negative associations in both groups between SWS% and learning the sensory-motor procedural memory task; () Negative associations in ASD but not in healthy controls; between S1% and declarative memory immediate recall; sensory-motor and cognitive procedural memory tasks and selective attention; () S2 spindle density (C3) is negatively correlated with RT in the selective attention only in healthy controls; () S2 spindle density (C3) negatively correlated with sensory-motor procedural memory during the learning phase only in ASD group

Maski et al.,; 2015 [99]

ASD

None

ASD and controls: 9–16 years

ASD: 22; Controls: 20

Experimental Case-Control Repeated Measures Design training session in the morning 30 minutes after habitual wake time after the night of sleep recording and a testing session in the evening

PSG. EEG (F1, F2, C3, Cz, C4, O1, and O2), EOG, and EMG.

Spectral power calculated for slow wave oscillation (0.5–1 Hz), delta (1–4 Hz), theta (4–7 Hz), alpha (8–11 Hz), sigma (12–15 Hz), and beta (16–20 Hz) frequency ranges.; S2 sleep spindles (Cz): 12–15 Hz, lasting 0.5–2.0 s, no amplitude criteria

Sleep-dependent memory consolidation (difference in performance (in %) between training and testing phases)

Less REM sleep in ASD compared to control group

() In both conditions ASD group performed more poorly than control group; () Both groups recalled better in the sleep condition compared to the wake condition

Slow oscillation power correlated with sleep dependent memory consolidation in the ASD group only

Tessier et al.,; 2015 [98]

ASD

None

ASD: 6–13; Controls: 7–12; Mean: 10.23; SD: 2.00

ASD: 13; Controls: 13

Correlational study

PSG. EEG (C3, C4, F3, F4, O1, and O2), EOG, and EMG.

S2 sleep spindles

Intelligence WISC-III.; Performance IQ (PIQ), verbal IQ (VIQ), and full scale IQ (FSIQ) scores.

Lower S2 spindle density (Fp1) in ASD group compared to control group

() VIQ positively correlated with S2 spindle duration (C4) in control group but not in; ASD group; () VIQ is associated with spindle density only in ASD group; () FSIQ is associated with spindle density only in ASD group

(c)

Reference	Disorder	Cognitive impairment	Age	Sample size	Study design	⁢Sleep measure		Cognitive measure (outcome/s)	Results
						Recording parameters	Spindles scoring		Sleep	Cognition	Sleep and cognition
Bruni et al., 2009 [106]	DD	None	DD: 8–16; Controls: 7–16	DD: 16; Controls: 11	Correlational study	PPSG 10–20 International system	Power spectra calculated for delta, theta, alpha, sigma, and beta Sleep spindles Scored during N2.	() Memory and learning transfer; () Reading test (speed and accuracy); () Writing test (accuracy); () Intelligence WISC-IIIR	Compared to healthy controls DD participants had the following: () Less stage-shifts per hour; () Lower N2%; () Less N3%; () Increase in power of frequency bands 0.5–3 Hz and 11-12 Hz during N2 and 0.5–1 Hz during N3; () Increased spindle density	Mean IQ DD: FSIQ: 93.9; VIQ: 90; PIQ: 98.9	Only in DD group: (1) Sigma power band in N2 was positively correlated with the memory and learning transfer reading test; reading test; () Spindle density was positively correlated with performance on the word reading test

(d)

Reference

Disorder

Cognitive impairment

Age

Sample size

Study design

Sleep measure

Cognitive measure (outcome/s)

⁢Results

Recording parameters

Spindles scoring

Sleep

Cognition

Sleep and cognition

Marca et al.,; 2011 [90]

ID

Costello syndrome (CS)

CS patients: Range: 18 months–31 years; Controls: 18 months–31 years

CS: 11; Controls: 22

Sleep Spindles: 12–14 Hz. Scored over all NREM stages

DQ; IQ

CS group had increased spindle activity between 13 Hz and 14 Hz; and between 14 Hz and 15 Hz compared to healthy controls

Selvitelli et al.,; 2009 [91]

ID

Malformations of cortical development (MCDs)

MCD; Mean: 35.7; SD: 12.2; Controls: Mean: 35.6; SD: 14.3

MCD: 10; Controls: 10

Correlational study

Not specified

Sleep spindles; 12–16 Hz. Occurring during S2.

Compared to control group, MCD group had; () higher proportion of unilateral sleep spindles; () an increased proportion of anterior and diffuse spindles

Shibagaki et al.,; 1982 [94]

ID

Congenital cerebral dysplasia ( = 10); Hydrocephaly ( = 3); Rubinstein-Taybi syndrome ( = 2); Down’s syndrome ( = 1); Silver’s syndrome ( = 1); Lesch-Nyhan syndrome ( = 1); Hallermann-Streiff syndrome ( = 1); Remaining subjects = unknown etiology

4 months–8 years

45

Descriptive study

PSG. EEG (F3-C3, F4-C4, F3-A1, F4-A2, C3-A1, C4-A2, O1-A1, and O2-A2), EOG, EMG, and ECG

Not specified

DQ; IQ

() 56% displayed REM burst during NREM with sleep spindles.; () 64% showed sleep spindles at the beginning or towards the end of REM sleep

No significant findings

Shibagaki and; Kiyono, 1983 [95]

ID

Down’s syndrome ( = 3); Hydrocephaly ( = 9); Holoprosencephaly ( = 2); Remaining subjects = unknown etiology

3–8 months

90

Descriptive study

PSG. EEG (F3-C3, F4-C4, F3-A1, F4-A2, C3-A1, C4-A2, O1-A1, and O2-A2), EOG, EMG, and ECG

S2 sleep spindles

DQ; IQ

() 42% had a ratio of more than 2.00 (# spindles longer than 0.4 s/# of spindles shorter than 0.4 s); () 15.6% had a ratio of 1.99–1.00 and; 6% had a ratio of 0.99–0.50; () 22% had a ratio of less than 0.50; () 14% had no sleep spindles

() Subjects with a ratio of less than 0.50 had significantly lower DQs than subjects with a ratio of more than 2.00; () Subjects with no sleep spindles at all had significantly lower DQs than subjects with a ratio of more than 2.00; () Subjects with a ratio of less than 0.50 or no sleep spindles had significantly lower DQs than subjects with a ratio of 1.99–1.00

Shibagaki, et al.,; 1986 [92]

ID

Cerebral palsy (CP); ( = 23)

CP: 4 months–5 years; Non-CP patients: 4 months–12 years

CP: 23; Non-CP patients: 39

Descriptive study

PSG (F3-A1, C3-A1, and O1-A1), EOG, ECG, respiration, and EMG

Not specified

DQ; IQ

() 13% of non-CP patients had no spindles or extremely low incidence of spindles; () 8% of CP cases showed no sleep spindles; () 22% of CP cases showed extremely low incidence of spindles; () 4.3% of CP cases showed extreme spindles

CP patients with indistinguishable sleep stages had lower DQs than CP patients with normal EEG patterns and non-CP patients with normal EEG patterns

Shibagaki, et al.,; 1980 [93]

ID

Holoprosencephaly ( = 1); Down’s syndrome ( = 2); Hydrocephaly ( = 8); Rubinstein-Taybi syndrome ( = 2); Prader-Willi syndrome ( = 2); Cri-du-chat syndrome ( = 2); Hallermann-Streiff syndrome ( = 1); Silver’s syndrome; ( = 1); Remaining subjects - unknown etiology

4 months–8 years

43

Descriptive study

PSG. EEG (F3-C3, F4-C4, F3-A1, C3-A1, F4-A2, and C4-A2), EOG, ECG, respiration, and EMG

Spindles measured during S2. Extreme spindles: 9-10 c/s, 50–120 μV

DQ

() 2.3% had no REM sleep; () 30% had no sleep spindles; () 4.6% had high voltage fast activity (20–30 c/s, 100–200 uV) without sleep spindles in wakefulness, S1, S2, and REM; () 7% had low voltage activity without spindles throughout nocturnal sleep; () 2.3% had indistinguishable stages with the presence of sleep spindles; () 2.3% had extreme spindles

() Patients with abnormal EEG patterns throughout S1–S4 had lower DQs than patients with abnormal EEG patterns only in S1-S2 and patients with normal EEG patterns; () Patients with abnormal EEG patterns in S1-S2 had lower DQs than patients with normal EEG patterns

Veneselli et al.,; 2001 [87]

ID

Late infantile neuronal ceroid lipofuscinosis (LINCL)

Range: 3–10

LINCL patients: 18

Descriptive study

PSG. EEG (10–20 International System of electrode placement)

Not specified

No sleep spindles were observed

(e)

Reference	Disorder	Cognitive impairment	Age	Sample size	Study design	⁢Sleep measure		Cognitive measure (outcome/s)	⁢Results
						Recording parameters	Spindles scoring		Sleep	Cognition	Sleep and cognition
Astill et al.,; 2014 [65]	None; (TPD)	None	Mean: 10.7; SD: 0.8	30	Experimental Repeated Measures Design	PSG EEG (Fpz, Cz), EOG, EMG	Artifact-free EEG across S2, S3 and S4; Fast spindles: frequency ≥ 12 Hz, Slow; spindles: frequency <12 Hz.	Sleep-dependent procedural memory task: finger sequence tapping tasks (speed and accuracy)	Average duration of slow waves at FPz was negatively correlated with density of fast spindles and positively correlated with density of slow	Accuracy was better if the interval contained sleep	() Higher SWS% was associated with increases accuracy; () Children with higher density of slow spindles had lower overall speed and accuracy whereas children with higher density of fast spindles had higher overall speed; () Children with higher density of slow spindles showed a stronger overnight increase in accuracy but not speed.; () Children with a longer average duration of slow waves had stronger overnight increase in accuracy but not speed.
Bódizs et al.,; 2014 [66]	None; (TPD)	None	15–22 years	24	Correlational study	PSG; 10–20 International system	Measured across stages S2–S4.	Fluid intelligence Raven’s progressive matrices test (RPMT); (IQ)	Subjects had normal sleep structure	IQ	Only in females, fast spindle density and fast spindle amplitude were positively correlated with IQ scores.
Chatburn et al.,; 2013 [63]	None; (TPD)	None	4.1–12.7 years	27	Correlational study	PSG (C3-A2 and C4-A1), EMG, and EOG	S2 sleep spindles	Stanford-Binet intelligence scale; NEPSY	Subjects had normal sleep structure	All intelligence and neurocognitive functioning was in the normal range	() Mean central spindle frequency was negatively correlated with nonverbal working memory, planning, and fine motor functioning; () Fast spindle density was positively correlated with narrative memory and negatively correlated with sensorimotor functioning and fine motor functioning
Doucette et al.,; 2015 [67]	None; (TPD)	None	2–5 years	10; 50% males	Correlational study Sleep was recorded over 1 night in the home environment	PSG	Slow sigma frequency range: 10–13 Hz; Fast sigma frequency range: 13.25–17 Hz	Processing speed; task: (RT)	Subjects had normal sleep structure	Average reaction time was 1408.8 ± 251.4 ms	RT significantly correlated with slow sigma power in a cluster of 16 electrodes in parietal regions
Geiger et al.,; 2011 [61]	None; (TPD)	None	Range: 9–12 years; Mean: 10.5; SD: 1.0	14; 57.1% males	Correlational study; Sleep was recorded over 2 nights separated by 1 or 2 weeks in a sleep laboratory	PSG. EEG 10–20 International system EOG and EMG	Mean all-night power spectra of stage N2 sleep.	Intelligence WISC-IV; Attention; task (RT)	Subjects had normal sleep structure	All results were in the normal range	() Sleep spindle peak frequency correlated negatively with full scale IQ; () Individual relative sigma power correlated positively with full scale IQ and fluid IQ
Gruber et al.,; 2013 [62]	None; (TPD)	None	Range: 7–11 years	29	Correlational study	PSG (F3, F4, C3, C4, P3, P4, O1, and O2), EOG, ECG, and EMG	Measured during all NREM artifact-free epochs.	Intelligence WISC-IV	Subjects had normal sleep structure	All results were in the normal range	Sleep spindle frequency was negatively associated with scores on the perceptual reasoning and working memory
Hoedlmoser et al.,; 2014 [64]	None; (TPD)	None	Range: 8–11 years	54	Correlational study	PSG 10–20 International system	Sleep spindles measured during N2 and N3.	Declarative memory consolidation task: word pair association task (RT); Intelligence WISC-IV	Subjects had normal sleep structure	() RTs for correctly remembered word pairs improved overnight; () Poorer retrieval scores observed in the morning after sleep	() Higher SpA positively correlated with better memory performance overall before and after sleep; () Children with higher IQ had higher SpA

Note. AASM = American Academy of Sleep Medicine; ADHD = attention deficit hyperactivity disorder; AS = Asperger’s syndrome; ASD = autism spectrum disorder; CP = cerebral palsy; CS = Costello syndrome; DD = developmental dyslexia; DQ = developmental quotient; ECG = electrocardiogram; EEG = electroencephalogram; EOG = electrooculogram; EMG = electromyogram; ID = intellectual disability; IQ = intelligence quotient; KITAP = test of attentional performance for children; MCD = malformations of cortical development; NEPSY = neuropsychological assessment; PSG = polysomnography; REM = rapid eye movement; RT = reaction time; SD = standard deviation; SpA = spindle activity; SWS = slow wave sleep; TDP = typically developing children; WISC = Wechsler intelligence scale for children.