Medical Neurosciences Brainstem 1 - Overview Brainstem – Part 1: Overview DAVID GRIESEMER, MD Professor of Neurosciences and Pediatrics Key Concepts: 1. The brainstem is divided into three regions in the rostral-caudal direction: midbrain, pons and medulla. 2. The brainstem is divided into three regions in the ventral-dorsal direction: basis, tegmentum and tectum. 3. The tegmentum at all levels contains the reticular formation, which is critical to the process of arousal and consciousness. 4. Prominent structures on the ventral aspect of the brainstem include the cerebral peduncles (midbrain), pontis basis (pons), and the pyramids and olives (medulla). 5. Prominent structures on the dorsal aspect of the brainstem include the cerebellum (pons). 6. Unlike spinal nerves which have mixed motor and sensory components, cranial nerves may possess pure motor function or pure sensory function. 7. Cranial nerves originate from nuclei which are arranged in vertical columns according to their function. 8. Like reflexes mediated by the spinal cord, the brainstem also has superficial, muscle stretch, and visceral reflexes. The brainstem from rostral to caudal consists of midbrain (mesencephalon), pons (metencephalon) and the medulla (myelencephalon). Approximately the diameter of a person’s smallest finger, the brainstem is a crucial part of the nervous system that contains ascending sensory and descending motor tracts, cranial nerve nuclei, secondary motor and sensory nuclei, autonomic pathways and centers, and the reticular formation. Medical Neurosciences Brainstem 1 - Overview Listed below are the major components of the brainstem; these will be more thoroughly described later: MOTOR COMPONENTS o Lower motor neurons Cranial nerves III, IV, VI, VII, XI and XII Motor component of CN V Nucleus ambiguous (CN IX, X, XI) o Upper motor neurons Red nucleus Superior and inferior colliculi Medial and lateral vestibular nuclei Medial pontine and medullary reticular formation o Descending motor pathways Corticospinal tract Rubrospinal tract Lateral and medial vestibulospinal tracts Pontine and medullary reticulospinal tracts Tectospinal tract SENSORY COMPONENTS o Secondary sensory nuclei Nuclei gracilis and cuneatus Nucleus solitarius Main sensory and descending nucleus of CN V Dorsal and ventral cochlear nuclei Accessory auditory nuclei Superior, inferior, medial and lateral vestibular nuclei Superior and inferior colliculi o Ascending sensory pathways Medial and lateral lemnisci Trigeminal and spinal lemnisci Solitario-thalamic tract Medical Neurosciences Brainstem 1 - Overview AUTONOMIC COMPONENTS o Parasympathetic preganglionic nuclei Edinger-Westphal (CN III) Superior (CN VII) and inferior (CN IX) salivatory nuclei Dorsal motor nucleus of CN X o Medullary autonomic “centers” – respiratory, pressor, depressor and vomiting center o Descending autonomic pathways – from the hypothalamus and limbic system CEREBELLAR CONNECTIONS o Superior cerebellar peduncle (brachium conjunctivum) – connects the midbrain with the cerebellum *? o Middle cerebellar peduncle (brachium pontis) – connects the pons and the cerebellum *? o Inferior cerebellar peduncle (restiform body) – connects medulla with the cerebellum BRAINSTEM DEVELOPMENT AND DESCRIPTION As noted above, the brainstem is divided from rostral to caudal into three regions: midbrain, pons, and medulla. Less apparent are three divisions from ventral to dorsal. A mid-sagittal cross-section view of the midbrain reveals the central canal. The canal helps to define these three regions. The very most ventral (anterior in human) region is called the basis. At the level of the midbrain, this region includes the cerebral peduncles, between which are located the small mammillary bodies (part of the hypothalamus). The anterior bulges of the pons and medulla are also part of the basis region. The enlargement of the ventral pons runs transversely, wraps around the brainstem, and connects via the middle cerebellar peduncles to the cerebellum on the dorsal side of the brainstem. The enlargement of the ventral medulla runs longitudinally. At the level of the medulla there are prominent, symmetrical, cylindrical elevations on both sides of the midline. These are called the pyramids, and they contain fibers Medical Neurosciences Brainstem 1 - Overview from the descending corticospinal tracts or pyramidal tracts1. Immediately lateral to the pyramids are large symmetric bumps called the olives (inferior olive), which contain large pre-cerebellar nuclei.2 The central canal separates the other two ventral-to-dorsal areas. The area ventral (anterior) to the central canal is called the tegmentum. Within the tegmentum, at the level of the midbrain are two symmetric, clearly defined, landmark nuclei (which unfortunately cannot be seen from an external view of the brainstem). These are the red nuclei, which help control voluntary movement, and the substantia nigra, which contains the brain’s largest concentration of dopamine-producing neurons. At the level of the pons and medulla, the reticular formation runs the full length of the tegmentum, extending up into the midbrain. Cross-section of brainstem at the level of midbrain (a), pons (b), and medulla (c). The region dorsal (posterior) to the central canal is called the tectum. At the level of midbrain the tectum is most fully developed. When viewed from the dorsal side, the tectum shows four symmetric hillocks: two superior colliculi and two inferior colliculi.3 Together these are called the quadrigeminal plate. At the level of pons, the area dorsal to the central canal does not develop tectum but undergoes intense cellular proliferation, producing neurons and glia that form the cerebellum and populate the inferior olivary nucleus.. While the central canal at the level of the midbrain changes minimally to become the cerebral aqueduct, the central canal at the level of the pons and midbrain changes dramatically. This is best understood if one considers the basal plate to function as a hinge and the alar plate to stretch like a rubber band. With development, the “hinge” of basal plate opens up and flattens, stretching the alar plate and rotating the sulcus limitans4 anteriorly. This model can be refined by also considering the sides of the neural tube to be hinges, with the axis of rotation along the sulcus limitans. The opening of these hinges creates a broad flat ventral floor for the fourth ventricle and further stretches the thinning “rubber band” of alar plate. This has the effect of rotating sensory nuclei (that arise from the alar plate) to a position lateral to the motor nuclei of the basal plate. The process creates a large rhomboid-shaped fourth ventricle and moves cranial nerve nuclei to the anterior portion of the brainstem. 1 At the midbrain level, the corticospinal tracts descend in the cerebral peduncles. At the junction of the medulla and the spinal cord, the corticospinal tracts decussate, or cross from one side to the other. This is the point at which fibers from the left side of the brain cross over to control the right side of the body, and vice versa. 2 3 The inferior olivary nuclei are easily recognized because of their rippled-ribbon configuration. The superior colliculi help coordinate eye and head movements with shifting gaze. The inferior colliculi help process auditory signals. 4 This is the longitudinal groove along the side of the central canal. It separates the ventral basal plate from the dorsal alar plate. Medical Neurosciences Brainstem 1 - Overview RETICULAR FORMATION The reticular formation is a phylogenetically ancient system that forms the core of the entire brainstem. It is responsible for maintaining consciousness, maintaining general muscle tone and posture, processing noxious (painful) stimuli, and regulating major visceral functions. The medial portion of the reticular formation has a predominantly motor function, and the lateral portion has mainly sensory function. Autonomic function is not precisely localized and is scattered through the entire reticular formation. The various components can be summarized in this manner: Motor components – maintenance of muscle tone and posture by means of: reticulospinal tract (in the pons) – which innervates extensor muscles reticulospinal tract (in the medulla) – which innervates flexor muscles Sensory components spinoreticular tract – which conveys slow pain Maintenance of consciousness – with the reticular formation “activating” the cerebral cortex in response to noxious stimulation Autonomic components – centers in the medulla to control Blood pressure Respirations Cardiac function Gastrointestinal function CRANIAL NUCLEI AND CRANIAL NERVES Because most cranial nerve nuclei are anteriorly located in the brainstem, most cranial nerves exit ventrally. Unlike sensory nerve roots in the spinal cord, even cranial nerves with sensory components emerge from the anterior side of the brainstem. Cranial nerves further differ from spinal nerves in that not all have mixed sensory and motor function like spinal nerve roots. Some cranial nerves have pure motor functions, some have pure sensory functions, and some are mixed. There is a strong correlation between function of cranial nerve nuclei and their position. Nuclei having similar functions are found in the same vertical columns. The columns are not continuous, however, and their vertical nature is somewhat compromised by distortions in the shape of the mature brainstem. There are three distinct columns of motor nuclei and three distinct columns of sensory nuclei. Medical Neurosciences Brainstem 1 - Overview MOTOR NUCLEI LOCATION SOMATIC MOTOR BRANCHIAL MOTOR SENSORY NUCLEI VISCERAL MOTOR GENERAL SENSORY SPECIAL SENSORY VISCERAL SENSORY Horizontal Level Midbrain Oculomotor (III) EdingerWestphal (III) Trochlear (IV) Pons Abducens (VI) Trigeminal (V) Facial (VII) Medulla Hypoglossal (XII) N. ambiguus (IX, X) Spinal accessory (XI) Superior salivatory (VII) Inferior Salivatory (IX) Dorsal mot. nucleus of vagus (X) Trigeminal: mesencephalic nucleus (V, VII, IX, X) Trigeminal: principal nucleus (V, VII, IX, X) Trigeminal: spinal nucleus (V, VII, IX, X) Vestibular (VIII) Cochlear (VIII) N. of the solitary tract (VII, IX, X) Cranial nerves visible from the ventral (anterior) side of the brainstem and spinal cord all arise from the same column of nuclei located within the neuraxis. Nerves include: pure motor (most medial in position) o oculomotor (III) o trochlear (IV) – which actually exits from the dorsal side of the brainstem o abducens (VI) o hypoglossal nerve (XII) o spinal nerve rootlets mixed motor and sensory (intermediate in position) o trigeminal nerve (V) o facial nerve (VII) o glossopharyngeal nerve (IX) Medical Neurosciences Brainstem 1 - Overview o vagus nerve (X) o accessory nerve (XI) – although located in this column, it is pure motor pure sensory (most lateral in position) o vestibular nerve (VIII) o cochlear nerve (VIII) Dorsal aspect of the brainstem Cranial nuclei envisioned from the dorsal side of the brainstem (with cerebellum removed) demonstrate the columnar organization of the brainstem nuclei. Motor nuclei are shown on the right half of the figure: somatic motor nuclei (most medial in position) o oculomotor (III) o trochlear (IV) o abducens (VI) o hypoglossal (XII) o motor neurons of spinal cord (not shown) branchial motor nuclei (more lateral in position, more likely to also have sensory components) o trigeminal motor (V) o facial motor (VII) o nucleus ambiguous (IX, X) o spinal accessory (XI) visceral motor nuclei (variable in location) o Edinger-Westfall (III) – actually dorsal to oculomotor nucleus, not medial as shown o superior salivatory (VII) – slightly below and lateral to the facial nucleus o inferior salivatory (IX) – below superior salivatory nucleus o dorsal nucleus of the vagus (X) – just lateral to the hypoglossal nucleus Sensory nuclei are shown on the left half of the figure. It is important to remember that sensory nuclei originate in the alar (dorsal) plate. However, with creation of the fourth ventricle (which separates the brainstem and cerebellum), the alar plate stretches at the midline and sensory nuclei rotate out to lay along side the motor nuclei on the basal plate. As a result the most medial sensory nuclei developing in the alar plate become the most lateral sensory nuclei of the mature brainstem, while the most lateral sensory nuclei in the early alar plate rotate the least. These become the most medial sensory nuclei in the mature Medical Neurosciences Brainstem 1 - Overview brainstem and they lie next to the most lateral motor nuclei. general sensory nuclei (medial in the alar plate, but more lateral in the mature brainstem) o trigeminal sensory (V) o spinal trigeminal (V) – continuous column with primary trigeminal sensory nucleus visceral sensory (lateral in the alar plate, but more medial in the mature brainstem) o nucleus of the solitary tract (VII, IX, and X) special sensory (variable in location) o vestibular (VIII) o cochlear (VIII) A review of this columnar organization of cranial nerve nuclei reveals the simple observation that some cranial nerves are purely motor or sensory and other cranial nerves are mixed: CRANIAL NERVE III IV V VI VII VIII IX, X XI XII MOTOR somatic, visceral Somatic Branchial Somatic branchial, visceral branchial, visceral Branchial Somatic COMPONENTS SENSORY general general, visceral (SVA) special general, visceral (GVA & SVA) At the end of the notes for this lecture is a comprehensive table summarizing cranial nerve classification, components, connections and targets. This summaries information that you will learn later as different levels of brainstem and functional systems are studied. REFLEXES Adding to established knowledge about reflexes at the spinal cord level, information about brainstem reflexes completes the clinician’s knowledge of testable reflexes: REFLEX AFFERENT NERVE SYNAPSE EFFERENT NERVE Superficial reflexes Corneal CN V Pons CN VII Medical Neurosciences Sneeze (nasal) Gag (pharyngeal) Upper abdominal Lower abdominal Cremasteric Plantar Anal Brainstem 1 - Overview CN V CN IX T7-10 T10-12 Femoral Tibial Pudendal Brain stem / upper cervical cord Medulla T7-10 T10-12 L1 S1-2 S4-5 CN V, VII, IX, X and C3-5 CN X T7-10 T10-12 Genitofemoral Tibial Pudendal Muscle stretch reflexes Jaw Biceps Triceps Brachioradialis Knee (patellar) Ankle (Achilles) CN V Musculocutaneous Radial Radial Femoral Tibial Pons C5-6 C7-8 C5-6 L3-4 S1-2 CN V Musculocutaneous Radial Radial Femoral Tibial Visceral reflexes Light Accommodation Ciliospinal CN II CN II Midbrain Occipital cortex T1-2 CN III CN III Cervical sympathetics Oculocardiac Carotid sinus Bulbocavernosus CN V CN IX Pudendal Medulla Medulla S2-4 CN X CN X Pelvic autonomic Bladder and rectal Pudendal S2-4 Pudendal and autonomics Pathologic reflexes Extensor plantar (Babinski) Plantar L3-S1 Extensor hallucis longus Medical Neurosciences COLUMN Somatic motor OLD SYSTEM MODALITY SE CENTRAL CONNECTIONS Visceral motor General sensory LMN branchial arches SVE GVE Parasympathetic GSA Facial sensation GVA Taste Sensory SVA Visceral sensory BRAINSTEM NUCLEI CRANIAL NERVES III, IV, VI III, IV, VI XII XII V V VII VII Facial muscles Nucleus ambiguus IX, X, XI Pharynx, larynx Edinger-Westphal III Motor cortex, corticobulbar tract TARGET Extraocular muscles Chewing muscles Ciliary Pupil constrictor Pterygopalatine Lacrimal glands Submandibular & sublingual glands VII Submandibular Inferior salivatory IX Otic Dorsal mot n of X X Intramural Heart, lung, gut Parotid gland Main sensory V V1, 2, 3 Trigeminal Epicritic -- face VPM - trigeminal lemniscus Spinal nucleus V V1, 2, 3 Trigeminal Protopathic -- face, pharynx, larynx VII Geniculate Anterior 2/3 tongue VPM via Solitariothalamic tract Nucleus solitarius: rostral portion IX Petrosal Posterior 1/3 tongue X Nodose Epiglottis IX Petrosal X Nodose Carotid, aortic body, sinus, baroreceptors, chemoreceptors, gut sensation Hypothalamus Nucleus solitarius: caudal portion Visceral sensory Hearing Lateral lemniscus, MGB Dorsal & ventral cochlear Balance Cortex, MLF, cerebellum, VST, reticular formation Superior, inferior, lateral & medial vestibular SSA Tongue Superior salivatory Hypothalamus Parabrachial nuclei Special sensory GANGLIA LMN myotomes Motor Branchial motor Brainstem 1 - Overview Spiral Cochlea Scarpa Vestibular apparatus VIII