Origin, synchronization, and propagation of sleep slow waves in children.

STUDY OBJECTIVES: Sleep slow wave activity, as measured using EEG delta power (<4 Hz), undergoes significant changes throughout development, mirroring changes in brain function and anatomy. Yet, age-dependent variations in the characteristics of individual slow waves have not been thoroughly investigated. Here we aimed at characterizing individual slow wave properties such as origin, synchronization, and cortical propagation at the transition between childhood and adulthood. METHODS: We analyzed overnight high-density (256 electrodes) EEG recordings of healthy typically developing children (N = 21, 10.3 ± 1.5 years old) and young healthy adults (N = 18, 31.1 ± 4.4 years old). All recordings were preprocessed to reduce artifacts, and NREM slow waves were detected and characterized using validated algorithms. The threshold for statistical significance was set at p = 0.05. RESULTS: The slow waves of children were larger and steeper, but less widespread than those of adults. Moreover, they tended to mainly originate from and spread over more posterior brain areas. Relative to those of adults, the slow waves of children also displayed a tendency to more strongly involve and originate from the right than the left hemisphere. The separate analysis of slow waves characterized by high and low synchronization efficiency showed that these waves undergo partially distinct maturation patterns, consistent with their possible dependence on different generation and synchronization mechanisms. CONCLUSIONS: Changes in slow wave origin, synchronization, and propagation at the transition between childhood and adulthood are consistent with known modifications in cortico-cortical and subcortico-cortical brain connectivity. In this light, changes in slow-wave properties may provide a valuable yardstick to assess, track, and interpret physiological and pathological development.

Local sleep: A new concept in brain plasticity.

Traditionally, sleep and wakefulness have been considered as two global, mutually exclusive states. However, this view has been challenged by the discovery that sleep and wakefulness are actually locally regulated and that islands of these two states may often coexist in the same individual. Importantly, such a local regulation seems to be the key for many essential functions of sleep, including the maintenance of cognitive efficiency and the consolidation of new skills and memories. Indeed, local changes in sleep-related oscillations occur in brain areas that are used and involved in learning during wakefulness. In turn, these changes directly modulate experience-dependent brain adaptations and the consolidation of newly acquired memories. In line with these observations, alterations in the regional balance between wake- and sleep-like activity have been shown to accompany many pathologic conditions, including psychiatric and neurologic disorders. In the last decade, experimental research has started to shed light on the mechanisms involved in the local regulation of sleep and wakefulness. The results of this research have opened new avenues of investigation regarding the function of sleep and have revealed novel potential targets for the treatment of several pathologic conditions.

Emotion Regulation Failures Are Preceded by Local Increases in Sleep-like Activity.

Emotion self-regulation relies both on cognitive and behavioral strategies implemented to modulate the subjective experience and/or the behavioral expression of a given emotion. Although it is known that a network encompassing fronto-cingulate and parietal brain areas is engaged during successful emotion regulation, the functional mechanisms underlying failures in emotion suppression (ES) are still unclear. In order to investigate this issue, we analyzed video and high-density EEG recordings of 20 healthy adult participants during an ES and a free expression task performed on two consecutive days. Changes in facial expression during ES, but not free expression, were preceded by local increases in sleep-like activity (1-4 Hz) in brain areas responsible for emotional suppression, including bilateral anterior insula and anterior cingulate cortex, and in right middle/inferior frontal gyrus (p < .05, corrected). Moreover, shorter sleep duration the night before the ES experiment correlated with the number of behavioral errors (p = .03) and tended to be associated with higher frontal sleep-like activity during ES failures (p = .09). These results indicate that local sleep-like activity may represent the cause of ES failures in humans and may offer a functional explanation for previous observations linking lack of sleep, changes in frontal activity, and emotional dysregulation.

Role of corpus callosum in sleep spindle synchronization and coupling with slow waves.

Sleep spindles of non-REM sleep are transient, waxing-and-waning 10-16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5-4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidation. Given these premises, here we set out to investigate whether total callosotomy may affect the generation and spreading of sleep spindles, as well as their coupling with sleep slow waves. To this aim, we analysed overnight high-density EEG recordings (256 electrodes) collected in five patients who underwent total callosotomy due to drug-resistant epilepsy (age 40-53, two females), three non-callosotomized neurological patients (age 44-66, two females), and in a sample of 24 healthy adult control subjects (age 20-47, 13 females). Individual sleep spindles were automatically detected using a validated algorithm and their properties and topographic distributions were computed. All analyses were performed with and without a regression-based adjustment accounting for inter-subject age differences. The comparison between callosotomized patients and healthy subjects did not reveal systematic variations in spindle density, amplitude or frequency. However, callosotomized patients were characterized by a reduced spindle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression.

Integrity of Corpus Callosum Is Essential for theCross-Hemispheric Propagation of Sleep Slow Waves:A High-Density EEG Study in Split-Brain Patients.

The slow waves of non-rapid eye movement (NREM) sleep reflect experience-dependent plasticity and play a direct role in the restorative functions of sleep. Importantly, slow waves behave as traveling waves, and their propagation is assumed to occur through cortico-cortical white matter connections. In this light, the corpus callosum (CC) may represent the main responsible for cross-hemispheric slow-wave propagation. To verify this hypothesis, we performed overnight high-density (hd)-EEG recordings in five patients who underwent total callosotomy due to drug-resistant epilepsy (CPs; two females), in three noncallosotomized neurologic patients (NPs; two females), and in a sample of 24 healthy adult subjects (HSs; 13 females). In all CPs slow waves displayed a significantly reduced probability of cross-hemispheric propagation and a stronger inter-hemispheric asymmetry. In both CPs and HSs, the incidence of large slow waves within individual NREM epochs tended to differ across hemispheres, with a relative overall predominance of the right over the left hemisphere. The absolute magnitude of this asymmetry was greater in CPs relative to HSs. However, the CC resection had no significant effects on the distribution of slow-wave origin probability across hemispheres. The present results indicate that CC integrity is essential for the cross-hemispheric traveling of slow waves in human sleep, which is in line with the assumption of a direct relationship between white matter integrity and slow-wave propagation. Our findings also revealed a residual cross-hemispheric slow-wave propagation that may rely on alternative pathways, including cortico-subcortico-cortical loops. Finally, these data indicate that the lack of the CC does not lead to differences in slow-wave generation across brain hemispheres.SIGNIFICANCE STATEMENT The slow waves of NREM sleep behave as traveling waves, and their propagation has been suggested to reflect the integrity of white matter cortico-cortical connections. To directly assess this hypothesis, here we investigated the role of the corpus callosum in the cortical spreading of NREM slow waves through the study of a rare population of totally callosotomized patients. Our results demonstrate a causal role of the corpus callosum in the cross-hemispheric traveling of sleep slow waves. Additionally, we found that callosotomy does not affect the relative tendency of each hemisphere at generating slow waves. Incidentally, we also found that slow waves tend to originate more often in the right than in the left hemisphere in both callosotomized and healthy adult individuals.

Reductions in perceived stress following Transcendental Meditation practice are associated with increased brain regional connectivity at rest.

Transcendental Meditation (TM) is defined as a mental process of transcending using a silent mantra. Previous work showed that relatively brief period of TM practice leads to decreases in stress and anxiety. However, whether these changes are subserved by specific morpho-functional brain modifications (as observed in other meditation techniques) is still unclear. Using a longitudinal design, we combined psychometric questionnaires, structural and resting-state functional magnetic resonance imaging (RS-fMRI) to investigate the potential brain modifications underlying the psychological effects of TM. The final sample included 19 naïve subjects instructed to complete two daily 20-min TM sessions, and 15 volunteers in the control group. Both groups were evaluated at recruitment (T0) and after 3 months (T1). At T1, only meditators showed a decrease in perceived anxiety and stress (t(18) = 2.53, p = 0.02), which correlated negatively with T1-T0 changes in functional connectivity among posterior cingulate cortex (PCC), precuneus and left superior parietal lobule. Additionally, TM practice was associated with increased connectivity between PCC and right insula, likely reflecting changes in interoceptive awareness. No structural changes were observed in meditators or control subjects. These preliminary findings indicate that beneficial effects of TM may be mediated by functional brain changes that take place after a short practice period of 3 months.

Measuring dispositional optimism in patients with chronic heart failure and their healthcare providers: the validity of the Life Orientation Test-Revised.

The Life Orientation Test-Revised (LOT-R) measures dispositional optimism (DO) - an individual difference promoting physical and psychological well-being in healthy adults (HAs) as well as in patients with chronic heart failure (CHF) and healthcare providers (HPs). Controversy has arisen regarding the dimensionality of the LOT-R. Whereas DO was originally defined as a one-dimensional construct, empirical evidence suggests two correlated factors in the LOT-R. This study was the first attempt to identify the best factor structure of the LOT-R in patients with CHF and HPs and to evaluate its measurement invariance among subsamples of patients with CHF, HPs, and a normative sample of HAs. Its validity was also evaluated in patients with CHF. The sample comprised 543 participants (34% HAs; 34% HPs; and 32% CHF patients). Congeneric, two correlated factor, and two orthogonal factor models for the LOT-R were compared by performing confirmatory factor analysis (CFA). Measurement invariance was evaluated by considering differential item functioning (DIF) among subsamples of HPs, patients with CHF, and HAs. In patients with CHF, validity was assessed by considering associations with anxiety and depression. The CFA demonstrated the superior fit of the two orthogonal factor model. Moreover, across patients with CHF, HPs, and HAs, the results highlighted a minimal DIF with only trivial consequences. Finally, negative but weak correlations of DO with anxiety and depression confirmed the validity of the LOT-R in patients with CHF. In summary, these findings supported the validity and suitability of the LOT-R for the assessment of DO in patients with CHF, HPs, and HAs.

Optimism's Explicative Role for Chronic Diseases.

The increasing interest about dispositional optimism's role in health status and its positive modulating effect on health outcomes has led to a remarkable scientific production in the last decade. To date lot is known for which diseases optimism is relevant, instead much less is known about how optimism interacts with other factors, both biological and psychological, in determining health status. The aim of this mini review is to explore the literature derived from clinical and experimental research assessing the associations between dispositional optimism and health status. Dispositional optimism can be considered as facet of personality that is cognitive in nature which holds the global expectation that the future will be plenty of good events. Optimists view desired goals as obtainable, so they often confront adversities in active manners resulting in perseverance and increased goal attainment. Only studies that explicitly included optimism and health outcomes, as measurable variables, and that reported a clear association between them have been reviewed. Cancer, cardiovascular disease, respiratory failure, and aging with multimorbidity were considered. Among the possible explicative hypotheses, two seem to best describe results: optimism may have a direct effect on the neuroendocrine system and on immune responses, and it may have an indirect effect on health outcomes by promoting protective health behaviors, adaptive coping strategies and enhancing positive mood. The research on optimism and health status has already shed light on important mechanisms regarding chronic diseases' management, however, further studies are needed to deepen the knowledge.