Spindle chirp and other sleep oscillatory features in young children with autism.

OBJECTIVES: To determine whether spindle chirp and other sleep oscillatory features differ in young children with and without autism. METHODS: Automated processing software was used to re-assess an extant set of polysomnograms representing 121 children (91 with autism [ASD], 30 typically-developing [TD]), with an age range of 1.35-8.23 years. Spindle metrics, including chirp, and slow oscillation (SO) characteristics were compared between groups. SO and fast and slow spindle (FS, SS) interactions were also investigated. Secondary analyses were performed assessing behavioural data associations, as well as exploratory cohort comparisons to children with non-autism developmental delay (DD). RESULTS: Posterior FS and SS chirp was significantly more negative in ASD than TD. Both groups had comparable intra-spindle frequency range and variance. Frontal and central SO amplitude were decreased in ASD. In contrast to previous manual findings, no differences were detected in other spindle or SO metrics. The ASD group displayed a higher parietal coupling angle. No differences were observed in phase-frequency coupling. The DD group demonstrated lower FS chirp and higher coupling angle than TD. Parietal SS chirp was positively associated with full developmental quotient. CONCLUSIONS: For the first time spindle chirp was investigated in autism and was found to be significantly more negative than in TD in this large cohort of young children. This finding strengthens previous reports of spindle and SO abnormalities in ASD. Further investigation of spindle chirp in healthy and clinical populations across development will help elucidate the significance of this difference and better understand this novel metric.

Neurology of Sleep.

Healthy sleep, including proper amounts in the 24-hour day/night period, is crucial for developing children. Sleep development in infants and children is characterized by increased amounts of sleep, including rapid eye movement and non-rapid eye movement (NREM) slow-wave sleep. Expected changes as well as deviations may contribute to sleep problems, which are common in typically developing children and very common in those with neurodevelopmental disorders and often are chronic. Periodic screening of children for sleep problems is important for timely and effective management of these.

Functional brain connectivity in electrical status epilepticus in sleep.

Electrical status epilepticus in sleep (ESES) is an age-related, self-limited epileptic encephalopathy. The syndrome is characterized by cognitive and behavioral abnormalities and a specific EEG pattern of continuous spikes and waves during slow-wave sleep. While spikes and sharp waves are known to result in transient cognitive impairment during learning and memory tasks performed during the waking state, the effect of epileptiform discharges during sleep on cognition and behavior is unclear. There is increasing evidence that abnormalities of coherence, a measure of the consistency of the phase difference between two EEG signals when compared over time, is an important feature of brain oscillations and plays a role in cognition and behavior. The objective of this study was to determine whether coherence of EEG activity is altered during slow-wave sleep in children with ESES when compared to typically developing children. We examined coherence during epochs of ESES versus epochs when ESES was not present. In addition, we compared coherence during slow-wave sleep between typically developing children and children with ESES. ESES was associated with remarkably high coherences at all bandwidths and most electrode pairs. While the high coherence was largely attributed to the spikes and spike-and-wave discharge, activity between spikes and spike-and-wave discharge also demonstrated high coherence. This study indicates that EEG coherence during ESES is relatively high. Whether these increases in coherence correlate with the cognitive and behavioral abnormalities seen in children with this EEG pattern remains to be determined.

Spindle activity in young children with autism, developmental delay, or typical development.

OBJECTIVE: To determine whether spindle activity differs in young children with and without autism. METHODS: We investigated differences in spindle density, duration, and oscillatory features in 135 young children with autism, developmental delay without autism (DD), or typical development (TD) and secondarily assessed the dimensional relationship between spindle density and both cognitive ability and social functioning. RESULTS: Compared to TD, both spindle density (Cohen d 0.93, 95% confidence interval [CI] 0.49-1.37) and duration (Cohen d 0.58, 95% CI 0.15-1.01) were significantly decreased in autism. Spindle density was also significantly reduced in autism compared to DD (Cohen d 0.61, 95% CI 0.13-1.09). Decreased spindle frequency in autism compared to both TD (Cohen d 0.47, 95% CI 0.04-0.90) and DD (Cohen d 0.58, 95% CI 0.10-1.06) did not survive correction. The DD group did not differ significantly from the TD group on any spindle parameter. These results, suggesting a relationship between spindle density and autism but not DD, were further illustrated in exploratory analyses, wherein nonverbal ratio IQ (RIQ) and the Vineland Socialization domain standard score were strongly correlated with spindle density in the full sample (r = 0.33, p ≤ 001 and r = 0.41, p ≤ 001, respectively) but not within group. After nonverbal RIQ was accounted for, the relationship between spindle density and Vineland Socialization remained statistically significant (r = 0.23, p < 0.01). However, Vineland Socialization scores accounted for the relationship between spindle density and nonverbal RIQ (r = 0.04, p = 0.67). CONCLUSION: In a large cohort of young children with autism, spindle density was reduced compared to groups of age-matched children with DD or TD. Alterations in the maturational trajectory of spindles may provide valuable insight into the neurophysiologic differences related to behavior in disorders of neurodevelopment.

Electroencephalogram Coherence Patterns in Autism: An Updated Review.

Electrophysiologic studies suggest that autism spectrum disorder is characterized by aberrant anatomic and functional neural circuitry. During normal brain development, pruning and synaptogenesis facilitate ongoing changes in both short- and long-range neural wiring. In developmental disorders such as autism, this process may be perturbed and lead to abnormal neural connectivity. Careful analysis of electrophysiologic connectivity patterns using EEG coherence may provide a way to probe the resulting differences in neurological function between people with and without autism. There is general consensus that electroencephalogram coherence patterns differ between individuals with and without autism spectrum disorders; however, the exact nature of the differences and their clinical significance remain unclear. Here we review recent literature comparing electroencephalogram coherence patterns between patients with autism spectrum disorders or at high risk for autism and their nonautistic or low-risk for autism peers.

Epilepsy and Autism.

Epilepsy and autistic spectrum disorder frequently coexist in the same individual. Electroencephalogram (EEG) epileptiform activity is also present at a substantially higher rate in children with autism than normally developing children. As with epilepsy, there are a multitude of genetic and environmental factors that can result in autistic spectrum disorder. There is growing consensus from both animal and clinical studies that autism is a disorder of aberrant connectivity. As measured with functional magnetic resonance imaging (MRI) and EEG, the brain in autistic spectrum disorder may be under- or overconnected or have a mixture of over- and underconnectivity. In the case of comorbid epilepsy and autism, an imbalance of the excitatory/inhibitory (E/I) ratio in selected regions of the brain may drive overconnectivity. Understanding the mechanism by which altered connectivity in individuals with comorbid epilepsy and autistic spectrum disorder results in the behaviors specific to the autistic spectrum disorder remains a challenge.

State-Dependent Differences in Functional Connectivity in Young Children With Autism Spectrum Disorder.

BACKGROUND: While there is increasing evidence of altered brain connectivity in autism, the degree and direction of these alterations in connectivity and their uniqueness to autism has not been established. The aim of the present study was to compare connectivity in children with autism to that of typically developing controls and children with developmental delay without autism. METHODS: We assessed EEG spectral power, coherence, phase lag, Pearson and partial correlations, and epileptiform activity during the awake, slow wave sleep, and REM sleep states in 137 children aged 2 to 6 years with autism (n = 87), developmental delay without autism (n = 21), or typical development (n = 29). FINDINGS: We found that brain connectivity, as measured by coherence, phase lag, and Pearson and partial correlations distinguished children with autism from both neurotypical and developmentally delayed children. In general, children with autism had increased coherence which was most prominent during slow wave sleep. INTERPRETATION: Functional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity.