Structural Brain Correlates of Sleep Microstructure in Spinocerebellar Ataxia Type 2 and its Role on Clinical Phenotype.

The influence of brain atrophy on sleep microstructure in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. The objective of the study is to explore the relationship between sleep microstructure and brain atrophy in SCA2 and its role in the clinical phenotype. Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI, and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. The sleep spindle activity exhibited a negative correlation with the number of trials required to complete the verbal memory test (VMT), and a positive correlation with the cerebellar volume, but the significance of the latter correlation did not survive multiple testing corrections. However, the causal mediation analyses unveiled that sleep spindle activity significantly mediates the association between cerebellar atrophy and VMT performance. Regarding REM sleep, both phasic EMG activity and REM sleep without atonia exhibited significant associations with pontine atrophy and disease severity measures. However, they did not demonstrate a causal mediation effect between the atrophy measures and disease severity. Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindle activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as disease biomarkers.Clinical trial registration number (TRN): No applicable.

Response of sleep slow oscillations to acoustic stimulation is evidenced by distinctive synchronization processes.

Closed-loop acoustic stimulation (CLAS) during sleep has shown to boost slow wave (SW) amplitude and spindle power. Moreover, sleep SW have been classified based on different processes of neuronal synchronization. Thus, different types of SW events may have distinct functional roles and be differentially affected by external stimuli. However, the SW synchronization processes affected by CLAS are not well understood. Here, we studied the effect of CLAS on the dissociation of SW events based on two features of neuronal synchronization in the electroencephalogram (topological spread and wave slope). We evaluated and classified individual SW events of 14 healthy subjects during a CLAS stimulated (STM) and a control night (CNT). Three main categories of SW events were found denoting (C1) steep slope SW with global spread, (C2) flat-slope waves with localized spread and homeostatic decline, and (C3) multipeaked flat-slope events with global spread. Comparing between conditions, we found a consistent increase of event proportion and trough amplitudes for C1 events during the time of stimulation. Furthermore, we found similar increases in post-stimulus spectral power in θ, ß, and σ frequencies for CNT vs STIM condition independently of sleep stage or SW categories. However, topological analysis showed differentiated spatial dynamics in N2 and N3 for SW categories and the co-occurrence with spindle events. Our findings support the existence of multiple types of SW with differential response to external stimuli and possible distinct neuronal mechanisms.

Association between brain morphology and electrophysiological features in Congenital Zika Virus Syndrome: A cross-sectional, observational study.

BACKGROUND: Intrauterine infection with the Zika virus (ZIKV) has been connected to severe brain malformations, microcephaly, and abnormal electrophysiological activity. METHODS: We describe the interictal electroencephalographic (EEG) recordings of 47 children born with ZIKV-derived microcephaly. EEGs were recorded in the first year of life and correlated with brain morphology. In 31 subjects, we tested the association between computed tomography (CT) findings and interictal epileptiform discharges (IED). In eighteen, CTs were used for correlating volumetric measurements of the brainstem, cerebellum, and prosencephalon with the rate of IED. FINDINGS: Twenty-nine out of 47 (62%) subjects were diagnosed as having epilepsy. Those subjects presented epileptiform discharges, including unilateral interictal spikes (26/29, 90%), bilateral synchronous and asynchronous interictal spikes (21/29, 72%), and hypsarrhythmia (12/29, 41%). Interestingly, 58% of subjects with clinical epilepsy were born with rhombencephalon malformations, while none of the subjects without epilepsy showed macroscopic abnormalities in this region. The presence of rhombencephalon malformation was associated with epilepsy (odds ratio of 34; 95% CI: 2 - 654). Also, the presence of IED was associated with smaller brain volumes. Age-corrected total brain volume was inversely correlated with the rate of IED during sleep. Finally, 11 of 44 (25%) subjects presented sleep spindles. We observed an odds ratio of 0·25 (95% CI: 0·06 - 1·04) for having sleep spindles given the IED presence. INTERPRETATION: The findings suggest that certain CT imaging features are associated with an increased likelihood of developing epilepsy, including higher rates of IED and impaired development of sleep spindles, in the first year of life of CZVS subjects. FUNDING: This work was supported by the Brazilian Federal Government through a postdoctoral fellowship for EBS (Talented Youth, Science without Borders), an undergraduate scholarship for AJR (Institutional Program of Science Initiation Scholarships, Federal University of Rio Grande do Norte, Brazil), by International Centre for Genetic Engineering and Biotechnology (CRP/BRA18-05_EC) and by CAPES (Grant number 440893/2016-0), and CNPq (Grant number 88881.130729/2016-01).

Association of sleep spindle activity and sleepiness in children with sleep-disordered breathing.

STUDY OBJECTIVES: The association of snoring and sleep-disordered breathing (SDB) with daytime sleepiness is well documented; however, the exact mechanisms, and especially the role of sleep microstructure that may account for this association remain incompletely understood. In a cohort of children with SDB, we aimed to compare sleep spindle activity between children with daytime sleepiness versus those without daytime sleepiness. METHODS: Children with SDB who reported daytime sleepiness were recruited and compared with age- and sex-matched SDB controls. Polysomnographic recordings were analyzed evaluating sleep spindle activity. A statistical comparison was carried out in both groups to assess the association between sleepiness and sleep spindle activity. RESULTS: Thirty-three children with SDB (mean age: 7.5 ± 1.7 years) were included, 10 with and 23 without daytime sleepiness. Spindle activity was lower in children with daytime sleepiness compared with those without; in stage N2, median (interquartile range) sleep spindle indexes were 77.5 (37.3) and 116.9 (71.2) (P = .015), respectively. CONCLUSIONS: Spindles were significantly reduced in children with SDB and daytime sleepiness. The exact mechanisms of this association remain unknown and future research is needed in order to establish the exact role of sleep spindle activity on daytime symptoms in children with SDB.

Sleep spindles: validated concepts and breakthroughs: [review]

INTRODUCTION: Sleep spindles, the hallmark of sleep synchronization in stage 2 non-REM sleep, are rhythmic and monomorphic waves, between 10 and 14 Hz, with a maximum amplitude in the vertex (Cz), with bilateral irradiation to central regions (C3 and C4). OBJECTIVE: In this article we present an overview of sleep spindles ranging from well established concepts of morphology, generation mechanisms, maturational features, abnormal patterns and pathological aspects since the knowledge is important to identify the normal and abnormal patterns. CONCLUSION: Centro-parietal and frontal spindle are normal pattern and extreme spindle is abnormal, mostly found in children mentally retarded up to 5 years-old. In this review research boundaries of memory consolidation, synaptic potentiation and brain plasticity were also presented.

INTRODUÇÃO: Fusos de sono, marco da sincronização do sono no estágio 2 do sono não-REM, são ondas rítmicas e monomórficas, entre 10 e 14 Hz, com amplitude máxima no vértex (Cz), e irradiação bilateral para áreas centrais (C3 e C4). OBJETIVO: Neste artigo apresentamos uma revisão sobre fusos de sono abrangendo conceitos bem estabelecidos de morfologia, mecanismos de geração, características maturacionais, padrões anormais e aspectos patológicos, uma vez que o conhecimento se faz necessário para a identificação de padrões normais e patológicos. CONCLUSÕES: Fusos centro-parietal e frontal são padrões fisiológiocs normais do sono fase 2 enquanto fusos extremos é um padrão patológico encontrado em crianças abaixo de 5 anos com retardo mental. Fronteiras da pesquisas quanto à consolidação da memória, potenciação sináptica e plasticidade cerebral também foram revisados.