Reticular activating system

The reticular activating system (RAS) is a crucial neural network within the brainstem that regulates consciousness, wakefulness, and the overall level of arousal. It acts as a gateway for sensory information reaching the cerebral cortex and plays an essential role in maintaining attention, alertness, and the sleep–wake cycle. Understanding the structure and function of this system is vital for comprehending the neurophysiological basis of consciousness and various clinical states of altered awareness.

Definition and Overview

General Definition

The reticular activating system, often referred to as the ascending reticular activating system (ARAS), is a collection of interconnected nuclei and pathways located within the brainstem. It functions as the primary regulator of arousal and consciousness by transmitting sensory signals to the thalamus and cerebral cortex. The RAS filters incoming sensory input, allowing the brain to prioritize significant stimuli while suppressing irrelevant information, thereby facilitating focused attention and responsiveness to the environment.

Structurally, the RAS is not a single anatomical entity but rather a diffuse network of neurons spread throughout the midbrain, pons, and medulla. Functionally, it integrates sensory, motor, and autonomic signals, contributing to the maintenance of alertness and behavioral responsiveness.

Historical Background

The concept of the reticular activating system emerged in the mid-20th century through the pioneering work of Giuseppe Moruzzi and Horace Magoun in 1949. Their experiments demonstrated that electrical stimulation of the brainstem reticular formation induced wakefulness in anesthetized animals, while lesions in this region resulted in profound sleep or coma. This discovery provided the first clear evidence that the brainstem plays a critical role in arousal and consciousness, reshaping the understanding of neural control of awareness.

Subsequent research expanded the definition of the RAS, identifying its connections with the thalamus, hypothalamus, and cerebral cortex. The recognition of multiple neurotransmitter systems within the RAS—such as cholinergic, noradrenergic, serotonergic, and dopaminergic pathways—further enhanced understanding of its complex role in regulating sleep, attention, and autonomic functions.

Functional Importance in Neurophysiology

The RAS serves as the interface between the sensory environment and cortical processing centers. By modulating cortical activity, it determines the brain’s readiness to respond to external stimuli. This system is fundamental to maintaining consciousness, as its impairment can result in reduced alertness, drowsiness, or coma. The RAS also participates in modulating emotional behavior, learning, and memory through its influence on cortical and limbic circuits. In essence, it coordinates the dynamic balance between sleep and wakefulness, enabling adaptive behavioral and physiological responses.

Anatomy of the Reticular Activating System (RAS)

Location and Structural Organization

The reticular activating system is located within the core of the brainstem, extending from the medulla oblongata through the pons and into the midbrain. It occupies a central position, forming a network of diffusely arranged neurons and fibers interspersed among cranial nerve nuclei and ascending sensory tracts. This arrangement allows the RAS to integrate multiple forms of sensory input and influence both higher cortical centers and lower motor systems.

• Position within the brainstem: The RAS extends longitudinally through the tegmentum of the brainstem, encompassing regions of the medullary, pontine, and midbrain reticular formation.
• Relationship with adjacent structures: It lies medial to the sensory and motor nuclei of cranial nerves and dorsal to the pyramidal tracts. Superiorly, it connects with thalamic nuclei and hypothalamic centers, while inferiorly it communicates with spinal cord pathways.

Major Components

The RAS consists of both ascending and descending components, which work in concert to regulate cortical arousal and autonomic control. The ascending component projects to the thalamus and cortex, promoting wakefulness and awareness, while the descending component modulates spinal reflexes and muscle tone.

• Reticular formation: A diffuse network of neurons forming the core of the brainstem. It serves as the central integrative structure of the RAS.
• Ascending pathways: These include fibers that project to the intralaminar nuclei of the thalamus and further to widespread cortical areas, facilitating arousal and attention.
• Descending pathways: These projections extend to the spinal cord and autonomic centers, influencing reflex activity and posture.

Connections and Neural Circuits

The RAS maintains extensive interconnections with various regions of the brain, forming complex feedback loops that coordinate sensory processing, alertness, and motor control. Its neural circuits ensure continuous communication between subcortical and cortical structures.

• Thalamic projections: The RAS transmits activating impulses to the intralaminar and reticular nuclei of the thalamus, which, in turn, relay signals to the cerebral cortex to maintain wakefulness.
• Hypothalamic and limbic connections: Pathways to the hypothalamus regulate autonomic functions and circadian rhythms, while connections with the limbic system influence emotion and motivation.
• Cortical projections: The diffuse cortical projections sustain background cortical activity essential for consciousness and cognitive processing.
• Interactions with sensory pathways: The RAS filters sensory input from ascending tracts such as the spinoreticular and spinothalamic pathways, enhancing relevant stimuli while suppressing irrelevant ones.

Neuroanatomical Subdivisions

Midbrain Reticular Formation

The midbrain portion of the reticular formation forms the upper segment of the reticular activating system and plays a critical role in maintaining consciousness and alertness. It contains important nuclei such as the pedunculopontine tegmental nucleus and the cuneiform nucleus, which are involved in modulating arousal and motor functions. The midbrain reticular neurons send ascending projections to the thalamus and hypothalamus, facilitating cortical activation and attention.

• Acts as a relay for sensory input ascending to the thalamus.
• Participates in the initiation and maintenance of wakefulness.
• Integrates visual, auditory, and somatosensory inputs for behavioral responses.

Pontine Reticular Formation

The pontine reticular formation lies within the pons and contributes to both ascending arousal and descending motor pathways. It contains two major divisions: the oral (rostral) and caudal pontine reticular nuclei. These regions are involved in the control of sleep stages, muscle tone, and coordination of reflex movements.

• Oral pontine nucleus: Involved in maintaining alertness and regulating transitions between wakefulness and non-REM sleep.
• Caudal pontine nucleus: Coordinates motor inhibition during REM sleep and contributes to the modulation of reflexes.
• Communicates with cranial nerve nuclei to integrate sensory and motor functions related to posture and balance.

Medullary Reticular Formation

The medullary segment represents the lowest part of the reticular formation, located within the medulla oblongata. It primarily regulates autonomic functions such as respiration, heart rate, and blood pressure, while also influencing muscle tone and reflex pathways. This region includes the gigantocellular nucleus and parvocellular nucleus, which form part of the descending reticulospinal tracts.

• Controls cardiovascular and respiratory centers critical for life support.
• Integrates sensory signals from the spinal cord to maintain homeostasis.
• Provides descending projections that modulate spinal motor neurons and autonomic output.

Intralaminar and Thalamic Nuclei Connections

The reticular activating system exerts its cortical influence largely through the intralaminar nuclei of the thalamus. These nuclei act as intermediaries, distributing activating signals throughout the cerebral cortex. This network sustains the background electrical activity required for consciousness and attention.

• The centromedian and parafascicular nuclei receive direct input from the brainstem reticular formation.
• Thalamic activation ensures synchronized cortical firing during wakefulness.
• Disruption of these circuits leads to impaired consciousness or coma.

Physiology and Mechanisms of Action

Ascending Reticular Activating System (ARAS)

The ascending reticular activating system is responsible for promoting arousal and maintaining cortical activity. It receives afferent sensory input from the spinal cord and cranial nerves, integrates it within the brainstem, and transmits it to higher brain centers. The ARAS does not convey specific sensory information but rather regulates the general excitability of the cortex, preparing it for sensory processing and conscious awareness.

• Pathway of sensory signal transmission: Collaterals from ascending sensory tracts, including the spinoreticular and spinothalamic pathways, activate reticular neurons that project to thalamic nuclei and subsequently to the cerebral cortex.
• Activation of cerebral cortex: Continuous stimulation of the cortex by ARAS fibers maintains wakefulness and attention. When activity in the ARAS decreases, the brain transitions into sleep or reduced alertness.
• Feedback regulation: The cerebral cortex provides reciprocal input to the reticular formation, allowing adaptive modulation of arousal based on environmental demands.

Descending Reticular Pathways

The descending component of the reticular formation, known as the reticulospinal tract, influences posture, motor control, and autonomic reflexes. It connects the brainstem with spinal cord neurons to regulate muscle tone and coordinate voluntary and involuntary movements.

• Influence on muscle tone and reflexes: Reticulospinal fibers modulate spinal interneurons and motor neurons, ensuring smooth execution of movement and reflex suppression when necessary.
• Integration with spinal cord motor neurons: Descending fibers interact with gamma motor neurons to adjust muscle spindle sensitivity, contributing to postural stability and locomotor activity.
• Autonomic regulation: Descending fibers influence sympathetic and parasympathetic centers in the spinal cord, thereby controlling visceral functions such as heart rate and gastrointestinal activity.

Neurotransmitters and Modulatory Systems

The physiological functions of the reticular activating system are mediated by multiple neurotransmitter systems that modulate cortical arousal, attention, and autonomic balance. These systems interact dynamically to maintain homeostatic control of wakefulness and sleep.

• Cholinergic system: Originating from the pedunculopontine and laterodorsal tegmental nuclei, it promotes wakefulness and rapid eye movement (REM) sleep.
• Noradrenergic system: The locus coeruleus provides widespread projections that enhance alertness and stress responses.
• Serotonergic system: The raphe nuclei modulate mood, sleep onset, and pain perception.
• Dopaminergic system: The ventral tegmental area contributes to motivation, reward, and cognitive engagement.
• Histaminergic system: The tuberomammillary nucleus of the hypothalamus supports sustained wakefulness by activating cortical neurons.

The combined action of these neurotransmitters creates a dynamic equilibrium between arousal and rest, ensuring adaptive responses to internal and external stimuli.

Functions of the Reticular Activating System

Regulation of Arousal and Consciousness

The most fundamental function of the reticular activating system (RAS) is to regulate arousal and maintain the state of consciousness. Through its ascending projections to the thalamus and cerebral cortex, the RAS determines the overall level of cortical excitability. When the RAS is active, cortical neurons exhibit desynchronized electrical activity characteristic of wakefulness. Conversely, decreased activity leads to drowsiness, sleep, or loss of consciousness.

• Wakefulness: Continuous excitation from the RAS keeps the cortex active, allowing awareness and interaction with the environment.
• Sleep and unconsciousness: Suppression of RAS activity induces synchronization of cortical neurons, leading to sleep or comatose states.
• Alertness control: The RAS dynamically adjusts cortical activity in response to sensory and environmental demands.

Sleep–Wake Cycle Control

The RAS works in conjunction with the hypothalamus and thalamus to regulate the sleep–wake cycle. It orchestrates transitions between sleep stages and wakefulness through interactions among cholinergic, noradrenergic, and serotonergic systems.

• Wake-promoting centers: The cholinergic neurons in the pontine tegmentum and the noradrenergic neurons of the locus coeruleus maintain arousal during wakefulness.
• Sleep-promoting centers: The ventrolateral preoptic nucleus of the hypothalamus inhibits RAS activity, allowing sleep onset.
• REM sleep regulation: The pontine reticular formation generates REM sleep by activating cholinergic neurons while suppressing motor activity through descending inhibitory pathways.

Attention and Sensory Filtering

The RAS plays a vital role in selective attention by filtering sensory inputs and prioritizing relevant stimuli. It prevents sensory overload by attenuating insignificant background signals while amplifying important sensory information that requires conscious awareness.

• Sensory gating: The RAS regulates the flow of afferent impulses to the cortex, enabling the brain to focus on significant stimuli.
• Startle response and alerting: Sudden sensory inputs trigger RAS activation, heightening alertness and readiness to respond.
• Habituation: Repeated non-threatening stimuli produce decreased RAS activity, reducing unnecessary cortical arousal.

Modulation of Autonomic Functions

The RAS contributes to the regulation of autonomic activities by influencing centers in the medulla and hypothalamus. It coordinates cardiovascular, respiratory, and gastrointestinal responses in relation to arousal levels.

• Increased alertness is accompanied by elevated heart rate, blood pressure, and respiratory rate.
• During sleep or relaxation, decreased RAS activity promotes parasympathetic dominance and reduced autonomic output.

Role in Emotional and Cognitive Processing

Through its interactions with the limbic system and prefrontal cortex, the RAS contributes to emotional regulation, motivation, and cognitive performance. Enhanced RAS activity facilitates learning, memory consolidation, and problem-solving by sustaining cortical attention.

• Emotional arousal enhances RAS activation, leading to increased alertness and readiness for action.
• Deficient activation results in cognitive fatigue, inattentiveness, and reduced mental efficiency.
• The RAS interacts with dopaminergic circuits to modulate reward-driven behavior and decision-making.

Integration with Other Brain Systems

Thalamocortical Network

The RAS communicates extensively with the thalamocortical system to regulate cortical arousal and sensory relay. The thalamus acts as a major hub for transmitting RAS impulses to the cerebral cortex, ensuring coordinated activation of widespread cortical regions during wakefulness.

• Intralaminar nuclei: Receive RAS input and distribute activating signals diffusely to the cortex.
• Reciprocal feedback: Cortical regions send projections back to the thalamus and RAS, modulating their activity according to cognitive demands.

Limbic System Connections

Connections between the RAS and limbic structures such as the amygdala, hippocampus, and cingulate gyrus integrate emotional and motivational states with arousal levels. This coordination allows emotions to influence wakefulness and attentional focus.

• Emotional stimuli processed by the amygdala can heighten arousal via RAS activation.
• Hippocampal inputs help synchronize arousal with learning and memory processes.
• Chronic overactivation of this pathway may contribute to anxiety and stress-related disorders.

Interaction with the Hypothalamus

The hypothalamus plays a central role in linking the RAS to circadian rhythm control and autonomic regulation. Hypothalamic nuclei integrate signals from the RAS with endocrine and visceral responses to maintain internal balance across sleep–wake cycles.

• The posterior hypothalamus promotes arousal through orexin and histamine release.
• The anterior hypothalamus facilitates sleep initiation by inhibiting RAS nuclei.
• Coordination between these regions maintains rhythmic fluctuations in alertness and body functions.

Coordination with the Cerebral Cortex

The RAS exerts its ultimate effect on consciousness through its projections to the cerebral cortex. Cortical neurons, in turn, provide feedback to the RAS, forming a bidirectional communication loop that regulates awareness and attention in real time.

• Activation of cortical columns: Sustained RAS input keeps cortical neurons in an excitable state conducive to perception and voluntary behavior.
• Cortical feedback: The cortex modulates RAS output based on cognitive context, emotional state, and environmental stimuli.
• This reciprocal relationship ensures adaptive behavioral responses and maintenance of alertness throughout daily activity.

Clinical Anatomy and Pathophysiology

Lesions and Disorders Affecting the RAS

Damage to the reticular activating system (RAS) can result in profound alterations in consciousness, arousal, and autonomic function. Because the RAS integrates ascending and descending neural pathways, its dysfunction can manifest in both neurological and systemic symptoms depending on the location and extent of the lesion.

• Coma and altered states of consciousness: Bilateral lesions of the brainstem reticular formation or thalamic projections can lead to coma or persistent vegetative states, characterized by loss of awareness but preserved autonomic function.
• Persistent vegetative state: Results from disconnection between the RAS and higher cortical centers, leading to wakefulness without conscious awareness.
• Hypersomnia and narcolepsy: Dysregulation of RAS neurotransmitter systems, especially hypocretin (orexin) deficiency, results in excessive daytime sleepiness and sudden onset of REM sleep.
• Attention-deficit disorders: Impaired modulation of RAS pathways reduces cortical activation, leading to difficulty maintaining attention and alertness.
• Autonomic dysfunctions: Damage to descending reticulospinal pathways can disrupt cardiovascular and respiratory control mechanisms, producing irregular heart rate or breathing patterns.

Impact of Trauma, Tumors, and Vascular Lesions

Structural damage to the brainstem or its connections can severely compromise the function of the RAS, with outcomes ranging from mild lethargy to irreversible coma. The severity of impairment depends on the specific nuclei and tracts affected.

• Traumatic brain injury (TBI): Diffuse axonal injury often involves the midbrain and upper pons, resulting in prolonged unconsciousness or post-traumatic coma.
• Tumors: Brainstem gliomas or metastatic lesions can compress the reticular formation, producing progressive drowsiness, cranial nerve deficits, and autonomic instability.
• Vascular lesions: Infarction of the paramedian midbrain or pontine arteries disrupts reticular circuits, leading to “locked-in” syndrome or coma.
• Inflammatory or demyelinating diseases: Conditions such as multiple sclerosis may involve the brainstem, impairing the integrity of RAS fibers and resulting in fluctuating alertness or fatigue.

Pharmacological and Toxin Effects on the RAS

The activity of the RAS can be profoundly altered by pharmacological agents and toxins that modify neurotransmission within its circuits. These substances can either enhance alertness or induce sedation depending on their mechanism of action.

• Stimulants: Drugs such as amphetamines, caffeine, and modafinil increase activity within the RAS, promoting wakefulness and alertness through catecholamine release.
• Sedatives and anesthetics: Barbiturates, benzodiazepines, and general anesthetics suppress neuronal firing in the RAS, resulting in sedation or loss of consciousness.
• Opioids: Depress the reticular formation and respiratory centers, contributing to drowsiness and hypoventilation in overdose conditions.
• Toxins: Neurotoxins such as carbon monoxide and organophosphates impair RAS function through hypoxia or neurotransmitter imbalance.

Diagnostic Evaluation

Clinical Neurological Examination

Evaluation of the RAS begins with an assessment of the patient’s level of consciousness, responsiveness, and arousal. These clinical signs reflect the functional integrity of ascending activating pathways and cortical connections.

• Glasgow Coma Scale (GCS): Used to quantify levels of consciousness through assessment of eye opening, verbal response, and motor response.
• Pupil response and cranial nerve testing: Evaluate brainstem function and integrity of reticular pathways.
• Motor and reflex assessment: Detects deficits in descending reticulospinal control of muscle tone and posture.

Electrophysiological Studies (EEG, Evoked Potentials)

Electroencephalography (EEG) provides an objective measure of cortical activity and its modulation by the RAS. Changes in EEG patterns reflect alterations in arousal and sleep states.

• EEG in wakefulness: Characterized by low-amplitude, high-frequency beta waves due to continuous RAS stimulation of the cortex.
• EEG in sleep or coma: Shows high-amplitude, low-frequency delta waves or burst-suppression patterns associated with reduced RAS output.
• Evoked potentials: Assess conduction through sensory pathways and their interaction with reticular and thalamic systems, providing insight into the integrity of ascending arousal circuits.

Neuroimaging Techniques (MRI, fMRI, PET)

Advanced imaging modalities help localize structural or functional abnormalities affecting the RAS. They are essential for diagnosing lesions or evaluating brain activity in altered states of consciousness.

• MRI (Magnetic Resonance Imaging): Detects structural lesions in the brainstem and thalamus, such as infarcts or tumors.
• fMRI (Functional MRI): Demonstrates dynamic activation of RAS-related regions during wakefulness, sleep transitions, or sensory stimulation.
• PET (Positron Emission Tomography): Measures metabolic activity, identifying hypometabolic states associated with coma or vegetative conditions.

Functional and Sleep Studies

Functional testing of RAS activity is often integrated with sleep studies and behavioral assessments to understand arousal regulation and sleep disorders.

• Polysomnography: Records EEG, eye movement, and muscle tone to evaluate sleep architecture and RAS-mediated transitions between REM and non-REM stages.
• Multiple Sleep Latency Test (MSLT): Measures the speed of sleep onset during daytime naps, identifying hypersomnia or narcolepsy.
• Brainstem auditory evoked responses (BAER): Used to assess brainstem integrity and conduction within auditory-reticular circuits.

Comprehensive evaluation using clinical, electrophysiological, and imaging techniques provides a detailed understanding of RAS function and is critical for diagnosing disorders of consciousness, attention, and sleep regulation.

Therapeutic and Research Perspectives

Pharmacological Modulation

Pharmacological interventions targeting the reticular activating system (RAS) are designed to modulate arousal levels, restore consciousness in pathological states, and regulate sleep–wake balance. These therapies act by influencing neurotransmitter systems that govern reticular and cortical activity.

• Stimulants and wake-promoting agents: Drugs such as modafinil, methylphenidate, and amphetamines enhance dopaminergic and noradrenergic transmission within the RAS, improving alertness and cognitive performance in disorders like narcolepsy and hypersomnia.
• Sedatives and anesthetics: Agents including benzodiazepines, propofol, and barbiturates suppress RAS activity by potentiating GABAergic inhibition, inducing sedation or anesthesia during medical procedures.
• Antidepressants and serotonergic drugs: Certain selective serotonin reuptake inhibitors (SSRIs) modulate RAS-linked serotonergic neurons to improve mood and normalize circadian arousal rhythms.
• Histaminergic and orexin-based therapies: Novel compounds targeting histamine H3 receptors and orexin agonists are being developed to treat excessive sleepiness and improve wakefulness.

Neurorehabilitation Approaches

Non-pharmacological therapies play a vital role in reactivating and stabilizing RAS function in patients recovering from traumatic brain injury, coma, or prolonged unconscious states. These interventions aim to re-establish neural connectivity and stimulate sensory-cognitive networks associated with arousal.

• Multisensory stimulation therapy: Combines auditory, tactile, and visual stimuli to enhance cortical responsiveness and promote recovery of consciousness.
• Physiotherapy and postural stimulation: Encourage proprioceptive input that activates ascending reticular pathways and aids in the restoration of alertness.
• Cognitive retraining: Structured cognitive tasks are employed to strengthen attentional control and executive functions mediated by RAS–cortical interactions.

Neurostimulation and Brain–Computer Interfaces

Advancements in neuromodulation have provided new therapeutic options for patients with severe disorders of consciousness. Electrical or magnetic stimulation of reticular and thalamic networks has shown potential in reactivating dormant neural circuits.

• Deep brain stimulation (DBS): Stimulation of the intralaminar thalamic nuclei has been shown to enhance arousal and responsiveness in patients with minimally conscious states.
• Transcranial magnetic stimulation (TMS): Non-invasive magnetic pulses targeting cortical–reticular pathways improve cortical activation and attentional performance.
• Vagus nerve stimulation (VNS): Indirectly activates reticular networks, improving alertness and reducing seizure frequency in epilepsy and post-coma recovery.
• Brain–computer interfaces (BCIs): Enable direct communication with cortical and reticular systems, facilitating neurofeedback and rehabilitation in patients with limited voluntary control.

Emerging Research in Consciousness Studies

Ongoing research into the reticular activating system is expanding understanding of the neural basis of consciousness. The integration of advanced imaging and computational modeling is helping delineate the RAS’s contribution to awareness and its dysfunction in neurological disorders.

• Functional connectivity mapping: Uses high-resolution fMRI and diffusion tensor imaging to visualize communication between RAS nuclei, thalamus, and cortex.
• Neurochemical profiling: Studies focus on quantifying neurotransmitter levels and receptor activity to identify biomarkers for altered consciousness.
• Artificial intelligence models: Simulations of RAS–cortical dynamics are being used to predict consciousness states and guide neurostimulation strategies.
• Regenerative medicine: Research on stem cell therapy and neurogenesis aims to restore damaged reticular networks and improve recovery after brain injury.

Comparative and Evolutionary Aspects

Reticular Systems in Non-human Species

The reticular activating system is conserved across vertebrate species, reflecting its fundamental role in maintaining alertness and survival. Comparative neuroanatomical studies demonstrate that the structural organization of the RAS parallels evolutionary complexity, with increasing specialization observed in higher mammals.

• Lower vertebrates (fish, amphibians): The reticular formation functions mainly as a primitive network controlling locomotion and reflex coordination, with limited influence on cortical activation.
• Birds and reptiles: Possess well-developed reticular and thalamic systems supporting wakefulness, vocalization, and sensory processing similar to early mammalian patterns.
• Mammals: Exhibit highly integrated RAS circuits that sustain complex behaviors, emotional responses, and higher-order consciousness.

Evolutionary Significance in Neural Integration

Evolutionarily, the RAS represents one of the earliest mechanisms for global neural regulation, providing a foundation for sensory processing and adaptive behavior. Its development allowed organisms to maintain vigilance, respond to environmental threats, and coordinate movement with perception.

• The emergence of the RAS enabled a transition from reflexive to goal-directed behavior through enhanced sensory prioritization.
• Expansion of cortical connections in primates allowed the RAS to participate in attention, learning, and emotional modulation.
• Comparative studies suggest that the evolution of consciousness is closely linked to the diversification of RAS–cortical interactions.

Understanding the comparative anatomy and evolution of the RAS offers valuable insights into how neural systems supporting arousal and awareness have been conserved and refined, laying the groundwork for complex cognitive and behavioral functions observed in humans.

References

1. Bear MF, Connors BW, Paradiso MA. Neuroscience: Exploring the Brain. 5th ed. Wolters Kluwer; 2024.
2. Kandel ER, Koester JD, Mack SH, Siegelbaum SA. Principles of Neural Science. 6th ed. McGraw Hill; 2021.
3. Guyton AC, Hall JE. Textbook of Medical Physiology. 15th ed. Elsevier; 2021.
4. Purves D, Augustine GJ, Fitzpatrick D, et al. Neuroscience. 7th ed. Oxford University Press; 2023.
5. Schiff ND. Recovery of consciousness after brain injury: mechanisms and therapeutic implications. Curr Opin Neurol. 2017;30(6):711-718.
6. Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol. 1949;1(1-4):455-473.
7. Parvizi J, Damasio A. Neuroanatomical correlates of brainstem coma. Brain. 2003;126(7):1524-1536.
8. Fuller PM, Saper CB, Lu J. The pontine and hypothalamic modulators of sleep and wakefulness. Curr Opin Neurobiol. 2007;17(6):748-753.
9. Steriade M, McCarley RW. Brainstem Control of Wakefulness and Sleep. 2nd ed. Springer; 2013.
10. Edlow BL, Takahashi E. Linking structural and functional connectivity of the human ascending arousal system. J Comp Neurol. 2018;526(13):2110-2134.