Infant sleep, viewed across the preterm-to-term continuum, is best understood not as a behavioral backdrop but as a developing neurobiological control system whose state organization offers a clinically accessible window onto central nervous system maturation. In this chapter we synthesize evidence on sleep across three contexts - the NICU, the post-discharge period, and community samples - and across three nested levels of organization: macro-architectural cycling between active, quiet, and indeterminate sleep; microstructural EEG features such as spindles, slow oscillations, and graphoelements; and the gradual emergence of circadian timing. We argue that infant sleep functions simultaneously as a mediator of brain development, a moderator of early vulnerability, and a marker of neurodevelopmental risk - a triple role that justifies treating sleep assessment as a core component of neonatal care rather than a supplementary concern. Yet the path from biomarker to bedside is far from frictionless. We examine the strengths and inferential limits of polysomnography, conventional and amplitude-integrated EEG, behavioral state coding, actigraphy, and autonomic-cardiorespiratory metrics, and we develop a reliability-validity-specificity framework for evaluating candidate biomarkers against the moving baselines of maturation, medication, illness, and environment. Throughout, we flag where current evidence supports causal mechanism, where it is merely correlational, and where the direction of effect may be bidirectional. The chapter closes with a three-step clinician-researcher bridge - assess, contextualize, decide - designed to translate multimodal sleep data into age-corrected, context-aware clinical decisions. Sleep, properly read, is not a research curiosity. It is a routine instrument of neurodevelopmental care.

Clinical confusion around restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and periodic limb movement disorder (PLMD) usually begins with a familiar sequence: the patient sleeps badly, the sleep study shows leg movements, and the report starts to sound like the diagnosis. The labels need more separation than that. RLS is diagnosed clinically from the history: an urge to move, often with uncomfortable sensations, brought out by rest, eased by movement, and worse in the evening or at night. PLMS are scored motor events. PLMD is reserved for the smaller group in whom those events plausibly account for sleep disturbance or daytime impairment after RLS, sleep-disordered breathing, narcolepsy, REM sleep behavior disorder, drug effects, and other neurological or medical causes have been considered. Biology is not a tidy dopamine story. Iron handling in the brain remains one of the more reproducible findings, although ferritin and transferrin saturation are only rough clinical proxies for central iron. Dopaminergic, adenosinergic, glutamatergic, spinal, autonomic, and genetic findings each explain part of the syndrome. Large genetic datasets, quantitative imaging, home movement recording, automated PLMS scoring, and autonomic measures have widened the field. Their immediate value is uneven: some help with mechanisms, some with measurement, and only a few currently change treatment decisions. Management still begins at the bedside. A typical RLS history, an incidental PLMS index, and possible PLMD lead to different choices. Iron indices should be checked early, medication and respiratory triggers need to be addressed, and dopamine agonist escalation should be avoided when augmentation is suspected. Current treatment is more cautious than older dopamine-centered practice: iron repletion when indicated, alpha-2-delta ligands for many chronic persistent cases, specialist use of opioids for severe refractory disease, and a selective role for device-based therapy. The chapter follows that clinical order rather than treating leg movement as a single target.

Central disorders of hypersomnolence (CDH), a group that includes narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and Kleine-Levin syndrome (KLS), are defined by excessive daytime sleepiness (EDS) and prolonged or fragmented sleep, but their impact extends well beyond wakefulness. Cognitive dysfunction is a core, disabling feature of the CDH spectrum, affecting attention, processing speed, memory, and executive function to varying degrees across subtypes. This chapter reviews current evidence on the nature, magnitude, neurobiological mechanisms, comorbidity interactions, treatment responsiveness, and clinical consequences of cognitive impairment in CDH, and aims to give the clinical neuroscientist and sleep specialist a practical framework.

Sleep is now recognized as a vital biological process with roles beyond rest, including neurodevelopment, memory, emotional regulation, metabolism, immune function, and neuroprotection. Advances in neuroscience and technology reveal that sleep is an active, multifaceted process involving multiple brain and body systems. This chapter explores how neural networks, waste clearance, circadian rhythms, immune responses, and cognition interact to influence brain health and disease. We examine sleep's connections to neurodegeneration, mental illness, aging, and cognitive resilience. We also highlight emerging directions, including personalized sleep medicine, digital mapping of sleep networks, AI-based diagnostics, sleep biomarkers, novel therapies, wearable technologies, and circadian interventions. Integrating genetics, computational modelling, and real-time monitoring could transform both basic and clinical sleep science. Ultimately, advancing sleep neuroscience will require a unified approach that links molecular mechanisms to behavior and disease, positioning sleep as a central target for enhancing cognition, preventing brain disorders, supporting mental health, and promoting overall well-being.

This chapter provides an exhaustive review of the neural substrates associated with insomnia and hyperarousal, considering the chronic disturbance of sleep from the complex perspective of a reciprocal biopsychosocial model. It focuses on several critical abnormalities observed on the structure and function of neuroanatomy, especially the hypersensitive reaction of the amygdala and insular cortex along with reduced reactivity of the prefrontal cortex that results in the development of emotional dysregulation and a continuous feeling of danger. At the circuitry level, it is possible to observe a substantial disturbance of the DMN and ECN connectivity. From a neurochemical point of view, this chapter describes the impact of the imbalances of GABA, serotonergic and noradrenergic systems in specific nuclei, such as the locus coeruleus and the tuberomammillary nucleus, together with HPA-axis overactivation and elevated cortisol levels that cause systemic cortical hyperarousal. As far as electrophysiological markers are concerned, there is a specific increase of beta wave activity in the waking resting-state as well as a decrease of restorative SWS and REM sleep stability. Lastly, this chapter gives some information about clinical relevance, especially about CBT-I, new neuromodulation strategies and brain-region specific pharmacotherapeutic options.

Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) is a somnipathy characterized by a physiological failure of skeletal muscle atonia during REM sleep. Such a brainstem pathway disruption, which directly affects the pontomedullary reticular formation, disrupts the descending inhibitory pathways that normally cause muscle paralysis. Patients then are much more likely to act out their dreams and will have complex, often violent dream-enactment behaviors that may cause injury and disrupt sleep continuity. Almost two decades of research have shown that RBD is potentially a crucial early indicator for synucleinopathies (brain diseases that are related to the accumulation of alpha-synuclein protein). These diseases include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Emerging biomarkers, neuroimaging results, and fluid-based biomarkers are discussed in the context of risk stratification and prediction of phenotypic pathophysiological transformation to overt neurodegenerative disease. Moreover, the chapter discusses how RBD provides a window for testing neuroprotective and disease-modifying therapies that may delay or prevent overt synucleinopathy. It also reviews current symptom management approaches that mix pharmacological treatment with non-pharmacological safety measures for injury prevention and neuromodulation technologies that target disrupted motor circuitry. Understanding the relationship between RBD and synucleinopathies offers a unique window into the earliest stages of neurodegeneration and presents new possibilities for early diagnosis, targeted treatment, and better patient outcomes.

Obstructive sleep apnea (OSA) has a broad and clinically important effect on cognition, most often impairing attention, executive function, memory, processing speed, and visuospatial ability, while language and immediate recall are relatively preserved. A substantial proportion of adults referred to sleep clinics already meet criteria for mild cognitive impairment at initial evaluation, particularly in moderate-to-severe OSA. This cognitive burden reflects multiple interacting mechanisms. Intermittent hypoxia promotes oxidative stress, mitochondrial dysfunction, and hippocampal injury through recurrent ischemia-reperfusion cycles. Sleep fragmentation disrupts slow-wave and REM sleep, impairing memory consolidation and glymphatic clearance. Neuroinflammation, endothelial dysfunction, and structural brain changes, including hippocampal atrophy, white matter hyperintensities, and reduced frontoparietal connectivity, may further compound injury over time. REM-related hypoxemia appears especially important for cerebrovascular injury and memory impairment. Measures such as hypoxic burden and oxygen desaturation indices may better capture brain risk than the apnea-hypopnea index alone. Older age, APOE ε4 genotype, obesity, hypertension, diabetes, depression, and prior cerebrovascular disease increase vulnerability and should guide screening and treatment priorities. Cognitive assessment in OSA should be domain-sensitive rather than based only on a single global cutoff. Effective therapy, especially positive airway pressure with adequate REM-period coverage, can improve alertness and selected cognitive outcomes, although attention may remain impaired despite improved oxygenation. In children, OSA can disrupt memory consolidation and working memory, and adenotonsillectomy often leads to only partial cognitive recovery. Cognition should therefore be considered a primary treatment outcome in both clinical care and future research.

Sleep, anxiety, and depression are interconnected processes that greatly influence mental health throughout life. Recent studies indicate that sleep issues are not just symptoms of mental illness but can also cause emotional and cognitive problems. Anxiety and depression can disrupt sleep patterns, and ongoing sleep difficulties can raise the likelihood of mood disorders. This reciprocal relationship involves neural pathways, neurochemicals, hormones, immune responses, and social factors. This chapter explores how sleep, anxiety, and depression interact from various scientific and clinical viewpoints. Topics include circadian rhythms, stress hormones, immune signalling, genetic and environmental effects, cognitive impairments, developmental factors, and new treatment options. Understanding these links is crucial for creating comprehensive approaches to simultaneously address sleep and mental health issues.

Sleep disorders are a growing global health issue with profound consequences on cardiovascular health, metabolic functioning, cognitive output and overall quality of life. Although there have been numerous clinical advances in brain-based treatments for sleep disorders, there are still a number of sleep disorders that are not well understood and need new treatment options to address the underlying neural mechanisms of sleep-wake regulation. Recent advances in neuroscience have highlighted neuromodulation as a promising treatment option for the complex neural mechanisms of sleep-wake dysfunction. This chapter provides an overview on the neurobiological basics of neuromodulation in sleep medicine, including neurobiological circuits, circadian processes of sleep, wakefulness and their disorders in brain and potential targeting biomarkers for brain stimulation. Present non-invasive neuromodulation strategies include transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), vagus nerve stimulation, etc.; new and invasive neuromodulation strategies such as deep brain stimulation (DBS) for insomnia, obstructive sleep apnea (OSA) and periodic leg movement disorder (PLMD). In this paper, we review the current level of evidence and provide an overview on the road ahead to bring brain stimulation to the daily practice of sleep medicine.

Insomnia is increasingly understood as a heterogeneous disturbance of sleep-wake regulation shaped by interacting cognitive, physiological, circadian, neurobiological, and perceptual mechanisms. This chapter develops a phenotype-informed framework for insomnia that distinguishes descriptive clinical presentations from underlying mechanistic dimensions and measurable biomarker domains. Core phenotypes reviewed include cognitive-emotional hyperarousal, objective short sleep duration, paradoxical insomnia and sleep-state misperception, circadian misalignment, autonomic dysregulation, sleep-depth instability, psychiatric comorbidity, and night-to-night sleep variability. Particular attention is given to neurocognitive biomarkers, including attention, executive function, working memory, episodic memory, cognitive variability, and subjective cognitive burden, with emphasis on how outcomes differ across insomnia phenotypes. It also examines electrophysiological and sleep microstructure markers, including high-frequency EEG activity, slow-wave activity, spindles, microarousals, cyclic alternating pattern, cardiopulmonary coupling, and Odds Ratio Product as emerging indicators of sleep depth and state instability. Autonomic, circadian, physiological, neuroimaging, wearable, and AI-enabled multimodal approaches are evaluated for their potential to refine mechanistic understanding and support future precision sleep medicine. Across domains, the chapter emphasizes that no single biomarker currently provides sufficient specificity for diagnosis or treatment selection. Instead, insomnia phenotyping is most useful as an integrative, mechanism-informed approach that can improve clinical formulation, guide individualized treatment emphasis, and identify future research priorities.

Sleep and circadian rhythms are crucial for regulating metabolism, cognitive function, and nightly brain repair. Chronobiology studies these biological timing systems by focusing on mechanisms such as neural synchrony, which underlies coordinated brain wave patterns that support transitions between sleep stages, memory encoding, and cognitive performance. Recent work in genetics, brain imaging, and computational modeling has uncovered specific pathways connecting circadian clocks to sleep regulation and neural network synchronization. For example, clock genes drive rhythmic cellular activity, and thalamocortical circuits create oscillatory patterns required for brain repair and memory consolidation. Disruptions in the integration of these mechanisms harm health by impairing neural communication and timing, leading to neurodegeneration, mental health issues, and metabolic or cognitive decline. This review explores how these systems develop and interact at the molecular and network levels, highlighting the suprachiasmatic nucleus as the central pacemaker, clock gene feedback loops as timekeepers, and thalamocortical circuits as mediators of neural synchrony. It also details how chronotherapy, light treatments targeting the circadian system, and AI-based sleep pattern analysis act on these mechanisms to benefit brain health. By clarifying how chronobiology and neuroscience intersect at the level of specific biological mechanisms, this review provides a comprehensive foundation for understanding and future research.

This chapter includes an extensive examination of the neuroanatomical and neurophysiological basis of dreaming and is primarily concerned with the phenomenology of rapid eye movement (REM) sleep. Relying on integrated findings from neuroimaging, electrophysiology, and neurochemical studies, the chapter describes that dreaming results from the interaction of brain regions such as the brainstem, thalamus, limbic system, and prefrontal cortex. The chapter underscores the central contribution of pontine cholinergic mechanisms to the generation of REM, combined with thalamocortical integration, to define perceptual and narrative features of dreams. Limbic activation in the amygdala and hippocampus is responsible for the emotional intensity and memory-related features of dream content, and relative prefrontal deactivation helps minimize logical constraint and promotes associative reasoning. Oscillatory dynamics, particularly theta and gamma activity, are considered important underpinnings of dream vividness and perceptual integration. With its focus on clinical conditions, including post-traumatic stress disorder (PTSD), depression, and REM sleep behavior disorder, the chapter provides a translational perspective beyond simple mechanistic models associated with the brain. The modulation of acetylcholine, serotonin, and norepinephrine is proposed to be one of the most important mechanisms of regulation with therapeutic potential. The chapter also addresses new domains such as dream neuropharmacology, neuromodulation, ethical implications, and cross-cultural perspectives of dream interpretation. More generally, it places dreaming as a neurobiologically driven, functionally relevant phenomenon with significance for emotional regulation, memory consolidation, and clinical intervention in sleep medicine.

This chapter covers the role of brain oscillations in shaping the microarchitecture of sleep and their role in physiological and pathological states. Neural oscillations (delta to gamma frequencies) are fundamental to the structure of sleep stages and play a central role in cognitive and restorative processes of the human brain. This chapter discusses how different oscillatory signatures characterize non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, with slow waves dominating deep sleep and desynchronization in REM sleep. Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are complementary to investigate sleep dynamics. EEG offers high temporal resolution in terms of oscillatory activity, and fMRI provides a spatial mapping of the network. The convergence of these modalities has provided new insights into sleep spindles, slow oscillations, and their association with large functional connections. Also emphasized in the chapter are the quantitative EEG metrics and advances in signal processing and machine learning that can help identify sleep stages and pathological patterns. The disruption of oscillatory dynamics in sleep disorders and neurodegenerative conditions is also explored as oscillatory biomarkers can be used as diagnostic and prognostic tools. Overall, the chapter highlights the implications of oscillatory dynamics as a common framework to connect sleep physiology with cognitive function and clinical applications, highlighting the potential for multimodal neuroimaging.

This chapter examines the intricate relationship between sleep and higher-order cognitive functions, particularly attention and executive control. Sleep is presented as a critical modulator of cognitive performance, influencing neural systems that underpin attentional regulation, working memory, and decision-making. The chapter highlights the vulnerability of attention to sleep deprivation, with impairments in sustained attention and processing efficiency linked to disruptions in dopaminergic and noradrenergic systems. The chapter also examines how sleep parameters and sleep architecture affect ADHD pathophysiology and symptomatology. Executive functions, including cognitive flexibility and inhibitory control, are shown to depend heavily on the integrity of prefrontal cortical networks, which are particularly sensitive to sleep disturbances. Neurobiological mechanisms underlying these relationships are explored, including thalamocortical circuitry, cholinergic modulation, and neuroendocrine influences such as cortisol dysregulation. Structural and functional neuroimaging studies reveal that insufficient sleep is associated with reduced prefrontal activity and altered connectivity, contributing to observable cognitive deficits. The chapter also discusses clinical implications, emphasizing the role of sleep interventions such as cognitive behavioral therapy in enhancing sleep quality, cognitive outcomes, and ADHD management. The bidirectional relationship between sleep and cognition is underscored, positioning sleep as a modifiable factor in optimizing cognitive resilience and mitigating neuropsychiatric risk.