User:Eugene M. Izhikevich/Proposed/Brainstem reticular activating system
The term “reticular formation” is an old term and is not used as frequently as before. The term was coined at a time when the functional identity of the many brainstem structures had not been explored. It was believed that the “reticular formation” was a net of interlaced neurons (thus the term, reticular = like a net) served the same function and could be viewed as a unitary “formation”. This view is no longer valid because we now know that many units within the so-called reticular formation have their distinct chemical identity, anatomical connectivity, and function, and thus may not fit into the mold of a unitary formation such as the reticular formation.
This article is intended to give an overview of the structure and function of the structures that once believed to be part of the brainstem reticular formation. We will aim at providing a big picture to aid the intended audience, and put the structure and function of the brainstem reticular formation structures in the context of the architectural and operational organization of the brainstem as a whole.
The brainstem is the stem of the brain. It is located at the junction between the cerebellum, spinal cord, and the higher brain structures such as the cerebral cortex ( Figure 1 ). This strategic location of the brainstem gives it a particularly important function, namely to serve as not only a connector, but also as a mediator, among these three structures. It contains pathways running down from the brain to the spinal cord and the cerebellum, and pathways running up to the brain from these structures. Because of its mere shape as a narrow structure at the crossroad between so important structures such as the cerebrum, the cerebellum, and the spinal cord, any small lesion in the brainstem will have devastating results.
It is essential to note that the brainstem’s function is far more than that of a relay station; it contains essential gray matter that receives incoming signals from, and projects to, structures such as the cerebral cortex, the hypothalamus, the spinal cord, the cerebellum and the basal ganglia, controlling many vital functions necessary for life.
Because of its connections with these structures, the brainstem is capable of modulating the function of the spinal cord, the cerebellum, and even the cerebral cortex. Therefore, any lesion in the brainstem will impair the function of each of these structures. For instance, lesions as small as a few millimeters in diameter can not only cut the connections from the brain to the spinal cord and cause paralysis, but also affect the up-going signals to the brain itself, and thus cause cognitive impairment. If this lesion is located in the upper brainstem, it may cause deep coma even if the lesion is as small as a pea.
The Architecture of the Brainstem2 ). It begins caudally in the medulla and ends rostrally at the level of the posterior commissure. As is the case elsewhere in the central nervous system, the brainstem consists of both white and gray matter. Figure 2a and b review the histological sections through the brainstem and point out key structures of the gray matter in the medulla, the pons and the midbrain
Brainstem White Matter
The white matter includes local connections interlinking various structures within the brainstem, but the bulk of the brainstem white matter consists of major descending and ascending tracts (Table 1: Major Descending and Ascending Tracts)
The descending tracts carry information from the higher brain structures to the cerebellum or the spinal cord, whereas ascending tracts carry information from the periphery, through the spinal cord, and towards the cerebellum and higher structures of the brain ( Figure 3 ).
Brainstem Gray Matter
Nuclei vary in their appearance via chemical staining, pathways and projections, and function, ranging from simple motor movements to the control of consciousness and sleep/wake cycles. Several nuclei are often tied together and, thus, function together in a system. Brainstem nuclei can be divided into those of the cranial nerves, tectum and those belonging to the reticular formation. ( Figure 4 ).
Cranial Nerves5 ).
These functions are served by brainstem nuclei known as cranial nerve nuclei (Table 2: Cranial Nerves and Their Function). Cranial nerves and their functions are well understood and have been discussed in varying neuroanatomy textbooks, and a discussion of their function and anatomy is beyond the scope of this text.
In addition to the cranial nerve nuclei, the brainstem gray matter also include the tectum, which literally means “roof” in Latin. The tectum is located dorsal to the midbrain and contains the superior and inferior colliculi. Most of the fibers from the optic tract project to the visual cortex via the lateral geniculate body, but a minority project to the superior colliculus and pretectal area. The superior colliculus and pretectal area are involved in visual processing and controlling eye movements towards visual stimuli. They project to numerous brainstem areas as well as to the association cortex (lateral parietal cortex and frontal eye fields). The inferior colliculus is involved in auditory processing. It receives inputs from various brainstem nuclei and projects to the medial geniculate nucleus of the thalamus, which relays auditory information to the primary auditory cortex. Both colliculi also have descending projections to the paramedian pontine reticular formation and spinal cord, and thus can be involved in responses to stimuli faster than cortical processing would allow.
The Reticular Formation
Recent advances in tracing techniques and neurochemical methods have changed such a view of the brainstem reticular formation. Although detailed knowledge about each of the reticular nuclei is still lacking, the reticular formation is now viewed as having functional and anatomical heterogeneity. Reticular nuclei such as the locus coeruleus, substantia nigra, raphe complex, parabrachial nucleus, periaqueductal gray, and nucleus cuneiforme were all considered as parts of the neuronal mesh of the reticular formation, but recent findings suggest that they are indeed distinct functional and anatomical units. Based on this information, it would be inappropriate to refer to these nuclei as components of one homogeneous structure, as the reticular formation has conventionally been defined ( Figure 6 ).
The new concept of reticular formation needs to be modified to refer to the heterogeneous collection of individual nuclei within the brainstem tegmentum to the exception of cranial nerve nuclei. The heterogeneity of the reticular nuclei is not a modern notion. For a long time, distinct nuclei within the reticular formation were defined based on their cytoarchitectonic features (Olszewski, 1954). These nuclei were also known to have different anatomical connections (Brodal, 1959). After the development of cytochemical techniques, the nomenclature of the reticular nuclei underwent a major revision: some of the old reticular nuclei became baptized as the monoaminergic nuclei because their main neurotransmitter was discovered to be dopamine, serotonin, or norepinephrine. Similarly, some other nuclei were distinguished as the cholinergic nuclei. Therefore, the complex organization of the reticular formation could be simplified by grouping the nuclei together based on their neurotransmitters.7.
The Function of the Brainstem Reticular Formation from an Evolutionary Perspective
The brainstem receives sensory signals from the rostral parts of the body, i.e., tactile, proprioceptive, and visceral information including the gustatory signals (Martin, 1996). Besides being a receptive sensory terminal for the head, it also maps the state of the viscera and the chemical profile of the entire body (Blessing, 1997). It integrates and relays to thalamus and cerebellum information from the proprioceptors located in the musculoskeletal frame of the body (Peterson, 1979; Rajakumar et al., 1992; Lingenhohl, Friauf, 1994; Lorincz, Fabre-Thorpe, 1997). It also relays and integrates vestibular and auditory signals (FitzPatrick, 1975; O'Mahony et al., 1994; Oertel, 1997; Balaban, Porter, 1998). Moreover, it receives the majority of spinal projections carried by unmyelinated C-fibers (Bowsher, 1957; Cervero, Iggo, 1980; Brown, 1982; Bernard, Besson, 1990; Craig, 1995; Willis, Westlund, 1997; Al-Chaer et al., 1997; Villanueva, Bernard, 1998; Sugimoto et al., 1998; Buritova et al., 1998; Mouton, Holstege, 1998). These fibers carry signals related to pain, temperature, and crude touch (Martin, 1996). However, there is evidence that they also detect changes in the internal milieu such as pH, pCO2, pO2, glucose concentration, osmolarity and presence of inflammatory agents (Moskowitz, 1991; Burnstock, Wood, 1996; Craig, 1997; Cesare, McNaughton, 1997). Therefore, it has been suggested that the channel of C-fibers should be considered as the channel for interoception (Craig, 1996).
The brainstem is, therefore, the first along the caudorostral axis of the central nervous system where signals from the viscera, the internal milieu, the vestibular organs, and the musculoskeletal frame are pooled within a network of heterogenous collection of nuclei. The brainstem is the first to map the overall state of the organism along the caudorostral extent of the central nervous system. This comprehensive “map” of the organism in the brainstem, makes it an important structure in the context of vital functions such as respiratory, cardiovascular, and gastroenteric functions whose control depends on an integration of information from the overall organism.
Interestingly, the accessibility of such a comprehensive map of the organism in the brainstem make it a suitable center in the central nervous system to modulate the state of wakefulness (Hobson, 1989) (Moruzzi, 1963; Steriade, 1992) and attention (Clark et al., 1987; Jones, 1991b; Chiang, Aston-Jones, 1993; Coenen, 1998; Usher et al., 1999), (Kinomura et al., 1996) which are necessary prerequisites for perceiving the world around us before any cognition can take place. In keeping with this view, small lesions in the brainstem reticular formation lead to the catastrophic state of coma and persistent vegetative state (Loeb, Stirling Meyer, 1965; Plum, Posner, 1980).
Brainstem Reticular Formation and ConsciousnessTable 3). The first is the fact that damage to the upper brainstem is a known cause of coma and persistent vegetative state, the disease states in which consciousness is most severely impaired. The second line of evidence originates from classical experiments, which suggested, either through lesions or electrical stimulation, that a part of the brainstem, i.e. the reticular formation, is important for maintaining wakefulness and an attentive state. Such evidence supports a general account of the relationship between brainstem and consciousness that can be summarized as follows: (a) the brainstem contains the reticular formation which is the origin of the ascending reticular activating system; (b) the engagement of the ascending reticular activating system activates the cerebral cortex; (c) the process of activating the cortex underlies wakefulness and attention; and (d) wakefulness and attention are indispensable constituents of consciousness. As seen in Table 3, this account has been faceted and polished throughout the last nearly 200 years.
In a recent study, we analyzed the location of lesions in 47 patients with brainstem strokes. In nine of these patients, stroke had caused coma. In all these patients the upper pons was affected. In 4, only the pontine, but not the midbrain, reticular formation area was damaged. The lesion overlap as shown in Figure 8 indicated that the area most important for the maintenance of consciousness might be located in the upper 1/3 of the pons.
This study suggested that the upper pontine tegmentum plays more of a role than midbrain in maintaining consciousness. Specific nuclei that may be involved are the PnO, LC, NR, LDT, and PBN (see Table 4 for abbreviations)
The modern view of the ascending activating system is that pathways for arousal and wakefulness originate from an interconnected network of small structures within the brainstem and the hypothalamus which work together to switch between states of sleep and wakefulness. For instance, the latest work suggests that the VLPO nucleus of the hypothalamus might be an important player in regulating this switch because it projects via inhibitory neurotransmitters to the monoaminergic neurons in the brainstem allowing for the sleep state to occur. In a Flip-flop model of sleep suggested by Clifford Saper the VLPO and ascending reticular activating system (ARAS) fight amongst each other and depending on who wins you are either asleep (VLPO) or awake (ARAS). This fight can also go on when you read a long article that may not be so engaging and stimulating. Hope it was not the case here!
|Lateral corticospinal tract||Primary Motor Cortex||Spinal Cord||Pyramids (cortiocomedullary jxn)||Movement of contralateral Limb|
|Anterior Corticospinal tract||Primary motor cortex||Cervical and thoracic cord||Control of bilateral axial and girdle muscles|
|Posterior Column-Medial Lemniscal Pathway||Dorsal Columns of Spinal Cord||Somatosensory cortext||Internal arcuate fibers (caudal medulla)||Vibration and joint-position sensation|
|Anterolateral Pathway||Spinothalamic Tract||Somatosensory cortex||Anterior commissure (Spinal cord)||Pain, temperature and crude touch|
|Sympathetic Pathway||Hypothalamus||Superior Cervical Ganglion||Sympathetic innervation to the eye|
|Rubrospinal tract||Red Nucleus||Cervical Cord||Ventral tegmental decussation (midbrain)||Movement of contralateral Limb|
|Medial Verstibulospinal Tract||Medial VST||Cervical and thoracic cord||Positioning of head and neck|
|Lateral Verstibulospinal Tract||Lateral VST||Spinal Cord||Balance|
|Tectospinal Tract||Superior Colliculus||Cervical Cord||Dorsal tegmental decussations (midbrain)||Coordination of head and eye movements|
|I Olfactory||Cribriform Plate||*Afferent olfactory information|
|II Optic||Optic canal||*Afferent visual from retina|
|III Oculomotor||Superior Orbital Fissure|| *Efferent motor to eye |
*Efferent parasympathetic to eye
|IV Trochlear||Superior Orbital Fissure||*Efferent motor to superior oblique muscle of the eye|
|V1 Opthalmic branch of Trigeminal Nerve||Superior Orbital Fissure||*Afferent sensory from upper face|
|V2 Maxillary branch of Trigeminal Nerve||Foramen Rotundum||*Afferent sensory from middle portion of face and upper jaw|
|V3 Mandibular branch of Trigeminal Nerve||Foramen ovale|| *Efferent motor to muscles of mastication|
*Afferent sensory from lower face and jaw
|VI Abducens||Superior Orbital Fissure||*Efferent motor to lateral rectus of the eye|
|VII Facial Nerve||Stylomastoid Foramen|| *Efferent motor to muscles of facial expression et al|
*Efferent parasympathetic fibers to lacrimal and mucosal glands
*Afferent taste from anterior tongue
*Afferent sensory from external ear
|VIII Vestibulocochlear||Internal Auditory Meatus||*Afferent vestibular and auditory information from inner ear|
|IX Glossopharyngeal||Jugular Foramen|| *Efferent motor to pharynx|
*Efferent parasympathetic to parotid gland
*Afferent taste from posterior tongue
*Afferent sensory from external ear
*Afferent sensory from pharynx, middle ear, carotid body and sinus
|X Vagus||Jugular Foramen|| *Efferent motor to muscles of palate, pharynx and larynx|
*Efferent parasympathetic to viscera
*Afferent taste from larynx
*Afferent sensory from external ear, meninges
*Afferent sensory from larynx, trachea, gut, aortic arch
|XI Accessory||Jugular Foramen||*Efferent motor to sernocleidomastoid and trapezius|
|XII Hypoglossal||Hypoglossal canal||*Efferent intrinsic and extrinsic motor to tongue|
|1836||Purkinje||Belgian munch and a scientist, introduced a theory of sleep [purkinje]. He regarded sleep as a deactivation of the cerebral cortex due to deafferentation of sensory inputs. Some decades later, a similar theory was introduced by Fredrik Bremer and became known as the deafferentation theory of sleep.|
|1875||Caton||Discovered the EEG|
|1875||Gayet||Midbrain lesions found in autopsy of a case with chronic lethargy. The patient was unresponsive and limp when aroused but lapsed into coma-like sleep when not actively stimulated. At the autopsy of this patient, the brain contained inflammation, softening and sclerosis of the central gray matter surrounding the third ventricle, aqueduct and also fourth ventricle.|
|1900||Ramon y Cajal||Distinguished two anatomically distinct systems of ascending paths in the brainstem. Before Cajal, Flechsig, Bechtrev, and Forel had pointed out a group of ascending fibers in the brainstem distinct from the classical lemnisci. This group of fibers became known as the central tegmental tract|
|1918||Von Economo||Center for physiological sleep in the rostral part of the brainstem near the aqueduct. Prolonged sleep followed by chronic lesions of encephalitis affecting the basal diencephalon and anterior midbrain, which did not involve afferent pathways to the cortex.|
|1924||Berger||Records the first human EEG signals|
|1930s||Hess||Induction of sleep with intraventricular injection of the ergotamine: Sleep that follows the ergotamine injection resembles the natural sleep with miosis can be explained as a shift toward the predominance of the parasympathetic over the sympathetic nervous system. He considered sleep as an effect to be due to an indirect inhibition due to the decrease in the autonomic control and not due to direct inhibition of somatic afferents.|
|1930s||Forbes||Discovery of the extralemniscal ascending system: “secondary response” to sciatic stimulation under deep barbiturate anesthesia, a response to be transmitted through the medial brainstem tegmentum and subthalamus and emerged widely over the cortex.|
|1930s||Berger||The activation of the EEG by sensory signals is related to the mental activities leading to the perception of the signals.|
|1935||Bremer||Pontomesencephalic transection of the brainstem (cervau isolé) gives rise to synchronization of the EEG as in deep sleep, whereas medullospinal transection (encephale isolé) does not.|
|1936||Derbyshire||There is a stage of normal sleep in unanesthetized cats that has the same EEG feature as in awake stage.|
|1936||Ingram, Barris, and Ranson|| Center for physiological sleep in the rostral part of the brainstem near the aqueduct. Prolonged sleep followed by chronic
lesions of encephalitis affecting the basal diencephalon and anterior midbrain, which did not involve afferent pathways to the cortex.
|1942||Moris and Dempsey||There is a diffuse thalamocortical recruiting system which is different from the main thalamocortical pathways relaying primary sensory information.|
|1948||Jasper||Stimulation of the periaqueductal portion of the midbrain, the posterior hypothalamus and the massa intermedia of thalamus give rise to a generalized acceleration of spontaneous electrocortical activity of the cortex simulating waking reactions.|
|1949||Moruzzi & Magoun||There is an excitable area within the brainstem reticular formation extending from the ventrolateral medulla to the upper mesencephalon (and to the posterior hypothalamus). Stimulation of this area gives rise to EEG desynchronizing, and damaging the same area leads to coma and synchronization of the EEG. In the animals with bilateral damages of the central core extending to the intralaminar thalamic nuclei, stimulation of the bulbar reticular formation, still could evoke some changes in the EEG pattern. EEG responses to bulbar stimulation were unaffected by bilateral lesions interrupting the medial and lateral lemnisci, and the spinothalamic tracts. The ascending reticular activating neurons are relayed in the intralaminar nuclei of thalamus.|
|1949||Lindsley||Observed the behavioral effect of the lesions of the reticular formation.|
|1951||Starzle||Intense stimulation of ischiatic nerve can desynchronize the EEG albeit the damage in the centromedian reticular formation but the EEG desynchronization does not last longer than the sensory stimulus.|
|1952||French and Magoun||Chronic, instead of acute, brainstem lesions of the pontomesencephalic, or mesencephalic reticular formation gave rise to behavioral somnolence, hypokinesia and lethargy in addition to the EEG synchronization. Sensory stimulation led to behavioral arousal and desynchronization of the EEG in these animals, but it only lasted as long as the stimulus lasted.|
|1952||Grastyan||Stimulation of nucleus tractus solitary produces synchronization of the EEG.|
|1953||Aserinksy and Kleitman||Discovered in humans the same phenomenon that was earlier discovered by Derbyshire. Later, this became known as REM stage|
|1953||French||If the main sensory pathways in the brainstem are bilaterally damaged, a sensory stimulation can affect the activity of the cortex through the reticular formation. The sensory stimulation in this case, produces slower potentials in wide areas of cortex, those being essentially in the associational cortices, and upon initiation, it is proceeded for a longer time. The laterally conducted main lemniscal sensory potentials are mainly recorded in the primary cortices and last as long as the stimulus is on. The extralemniscal conduction has a common transport pathway for all sensory modalities, as if the modalities have been converged together and have lost their identity in this pathway.|
|1955||Segundo||Stimulation of some particular areas of the cortex (i.e. some associational cortices and limbic structures) could produce behavioral alertness and arousal in unanesthesized monkeys. The excitable cortical areas have strong projections to the reticular formation.|
|1956||Roger||Destruction of vagus, cochleovestibular, optic or olfactory nerves do not cause synchronization of the EEG but destruction of trigeminal ganglion does so.|
|1959||Batini||As in Roger’s preparation the trigeminal and spinal input was blocked, but the vagal input to the upper reticular formation was no longer intact. The EEG pattern in the midpontine pretrigeminal preparation was an irreversible de-synchronized one.|
|1959||Magni||Selective inhibition of the medullary reticular formation, by injecting barbiturate in the vertebral circulation, gives rise to EEG activation.|
|1960||Batsel||EEG desynchronization can be observed in the animals a couple of weeks after mesencephalic transection.|
|1980s||Llinas and Steriade||Intracellular recordings show that thalamic cells as well as some cortical neurons, had the ability of generating oscillatory waves of electrical activity, and that this ability of the cells was intrinsic and independent from the external stimulation.|
|1996||Barth & McDonald||Stimulation of posterior intralaminar thalamic nuclei (PIL) gave rise to modulation of the fast oscillatory activity of the auditory cortex. Fast oscillation in the auditory cortex could be recorded following the lesion of PIL. Fast oscillation of the cortical neurons was generated intracortically independent from the subcortical input. In other words, the role of intralaminar nuclei, rather than driving the cortical oscillations, is to coordinate the oscillations between different cortical regions. It’s become more obvious that the desynchronization of the cortical activity by the ARAS is actually synchronization of the (desynchronized) fast oscillatory activities in the cortex, thalamus and in the cortico-thalamic systems (Steriade 1996). Information delivered to the cortex through the lateral lemniscal system was essential for the perception, recognition, discrimination and localization of different sensory modalities, whereas the medially conducted sensory input to the cortex was functionally important in, what they described as, initiating and maintaining the conscious state that provides the necessary background|
|1996||Kinomura||Regional blood flow in the intralaminar thalamic nuclei and in the mesencephalic reticular formation increases during tasks requiring alertness and attention|
|1996||Munk||MRF stimulation facilitates fast oscillatory activity of cortex and enhances the stimulus-specific synchronization of spatially separated pools of cortical neurons in response to visual stimulation of activity without which no integrated sensory, motor or adaptive function would be possible.|
|1998/9||Hypocretin / orexin discovered. Role of hypothalamic nuclei in the maintenance of consciousness emphasized. Lack of hypocretin / orexin type 2 receptors related to narcolepsy|
|4||Trochlear||LDT||laterodorsal tegmental nucleus|
|5||Trigeminal - motor||Mlf||medial longitudinal fasciculus|
|6||Abducens||NTS||nucleus tractus solitarius|
|8||Vestibulocochlear||PAG||periaqueductal gray matter|
|CST||cerebrospinal tract||PoC||pontin caudalis|
|CU & GR||cuneate and gracile nuclei||PoO||pontin oralis|
|CUN||cuneiform||PPTg-pc||pedunculopontine tegmental nucleus pars compacta|
|DMN||deep mesencephalic nucleus||PPTg-pd||pedunculopontine tegmental nucleus pars dissipatus|
|DMV||dorsal motor nucleus of Vagus||RN||red nucleus|
|DRN||dorsal medullary reticular complex||SCol||superior colliculus|
|EW||Edinger-Westphal||SNpc||substantia nigra pars compacta|
|GC||Gigantocellularis||SNpr||substantia nigra pars reticulata|
|ICol||inferior colliculus||Sol||solitary nucleus|
|INT||intercollicular||TG||Trigeminal nucleus - sensory|
|IRt||intermediate reticular zone||VRN||ventral reticular complex|
- Batini C, Moruzzi G, Palestini M, Rossi GF, Zanchetti A (1958) persistent pattern of wakefulness in the pretrigeminal midpontine preparation. Science 128:30-32.
- Batini C, Moruzzi G, Palestini M, Rossi GF, Zanchetti A (1959) Effects of complete pontine transections on the sleep-wakefulness rhythm: the midpontine pretrigeminal preparation. Arch Ital Biol 97:1-12.
- Bremer F (1935) Cerveau "isol," et physiologie du sommeil. CRSocBiol 118:1235-1241.
- Brodal A (1959) The reticular formation of the brain stem: anatomical aspect and funcional correlation. Edinburgh: The William Ramsay Henderon Trust.
- French JD, Magoun HW (1952) Effect of chronic lesions in central cephalic brain stem of monkeys. Archives of Neurology and Psychiatry 68:591-604.
- Kinomura S, Larsson J, Guly†s B, Roland P (1996) Activation by attention of the human reticular formation and thalamic intralaminar nuclei. Science 271:512-515.
- Kohnstamm O, Quesnel F (1909) Centrum receptorium der Formatio reticularis und gekreuzt aufsteigende Bahn. DtschZNervenheilk 36:182-188.
- Lindsley DB, Schreiner LH, Knowles WB, Magoun Ms, Magoun HW (1950) Behavorial and EEG changes following chronic brain stem lesions in the cat. Electroencephalogr Clin Neurophysiol 2:483-498.
- Llinas RR, Par D (1991) Of dreaming and wakefulness. Neuroscience 44:521-535.
- Magoun HW, French JD, Von Amerongen FK (1952) An activating system in brain stem of monkey. Archives of Neurology and Psychiatry 68:577-590.
- Morison RS, Dempsey EW (1942) A study of thalamo-cortical relations. Am J Physiol 135:281-292.
- Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1:455-473.
- Moruzzi G, Magni F, Rossi GF, Zanchetti A (1959) EEG arousal following inactivation of the lower brain stem by selective injection of barbiturate into the vertebral circulation. Arch Ital Biol 97:33-46.
- Munk MHJ, Roelfsema PR, Kînig P, Engel A, Singer W (1996) Role of reticular activation in the modulation of intracortical synchronization. Science 272:271-274.
- Parvizi, J. and Damasio, A.R. (2003): Differential distribution of calbindin D28K and parvalbumin among functionally distinctive sets of structures in the primate brainstem. Journal of Comparative Neurology, 462(2):153-167.
- Parvizi J. and Damasio A.R. (2001): Consciousness and the brainstem. Cognition, 79(2): 135-160.
- Parvizi, J. and Damasio, A.R. (2003): The neuroanatomical correlates of brainstem coma. Brain, 126, 1524-1536.
- Scheibel ME (1960) Axonal efferent patterns in the bulbar reticular formation. Anatomical Records:362-362.
- Sprague JM, Levitt M, Robson K, Liu CN, Stellar E, Chambers WW (1963) A neuroanatomical and behavioral analysis of the syndromes resulting from midbrain lemniscal and reticular lesions in the cat. Arch Ital Biol 101:225-295.
- Steriade M (1993) Central core modulation of spontaneous oscillations and sensory transmission in thalamocortical systems. [Review] [62 refs]. Curr Opin Neurobiol 3:619-625.