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Lesions at and around the stylomastoid foramen are the commonest abnormality of the facial nerve [VII] and usually result from a viral inflammation of the nerve within the bony canal before exiting through the stylomastoid foramen. Typically the patient has an ipsilateral loss of motor function of the whole side of the face. Not only does this produce an unusual appearance, but it also complicates chewing of food. Lacrimation and taste may not be affected if the lesion remains distal to the greater petrosal and chorda tympani branches that originate deep in the temporal bone. In the clinic Trigeminal neuralgia (tic douloureux) is a complex sensory disorder of the sensory root of the trigeminal nerve. Typically the pain is in the region of the mandibular [V3] and maxillary [V2] nerves, and is usually of sudden onset, is excruciating in nature, and may be triggered by touching a sensitive region of skin. The etiology of trigeminal neuralgia is unknown, although anomalous blood vessels lying adjacent to the sensory route of the maxillary [V2] and mandibular [V3] nerves may be involved. If symptoms persist and are unresponsive to medical care, surgical exploration of the trigeminal nerve (which is not without risk) may be necessary to remove any aberrant vessels. In the clinic The scalp has an extremely rich blood supply from the external carotid arteries, so lacerations of the scalp tend to bleed profusely. Importantly, scalp bleeding is predominantly arterial, because of two reasons. First, in the erect position the venous pressure is extremely low. Second, the vessels do not retract and close when lacerated because the connective tissue in which they are found holds them open. In the clinic Fractures of the orbit are not uncommon and may involve the orbital margins with extension into the maxilla, frontal, and zygomatic bones. These fractures are often part of complex facial fractures. Fractures within the orbit frequently occur within the floor and the medial wall; however, superior and lateral wall fractures also occur. Inferior orbital floor fractures are one of the commonest types of injuries. These fractures may drag the inferior oblique muscle and associated tissues into the fracture line. In these instances, patients may have upward gaze failure (upward gaze diplopia) in the affected eye. Medial wall fractures characteristically show air within the orbit in radiographs. This is due to fracture of the ethmoidal labyrinth, permitting direct continuity between the orbit and the ethmoidal paranasal sinuses. Occasionally, patients feel a full sensation within the orbit when blowing the nose. In the clinic Horner’s syndrome is caused by any lesion that leads to a loss of sympathetic function in the head. It is characterized by three typical features: pupillary constriction due to paralysis of the dilator pupillae muscle, partial ptosis (drooping of the upper eyelid) due to paralysis of the superior tarsal muscle, and absence of sweating on the ipsilateral side of the face and the neck due to absence of innervation of the sweat glands. Secondary changes may also include: ipsilateral vasodilation due to loss of the normal sympathetic control of the subcutaneous blood vessels, and enophthalmos (sinking of the eye)—believed to result from paralysis of the orbitalis muscle, although this is an uncommon feature of Horner’s syndrome. The orbitalis muscle spans the inferior orbital fissure and helps maintain the forward position of orbital contents. The commonest cause for Horner’s syndrome is a tumor eroding the cervicothoracic ganglion, which is typically an apical lung tumor.

A surgically induced Horner’s syndrome may be necessary for patients who suffer severe hyperhidrosis (sweating). This often debilitating condition may be so severe that patients are confined to their home for fear of embarrassment. Treatment is relatively straightforward. The patient is anesthetized and a bifurcate endotracheal tube is placed into the left and right main bronchi. A small incision is made in the intercostal space on the appropriate side, and a surgically induced pneumothorax is created. The patient is ventilated through the contralateral lung. Using an endoscope the apex of the thoracic cavity can be viewed from inside and the cervicothoracic ganglion readily identified. Obliterative techniques include thermocoagulation and surgical excision. After the ganglion has been destroyed, the endoscope is removed, the lung is reinflated, and the small hole is sutured. In the clinic Examination of the eye Examination of the eye includes assessment of the visual capabilities, the extrinsic musculature and its function, and disease processes that may affect the eye in isolation or as part of the systemic process. Examination of the eye includes tests for visual acuity, astigmatism, visual fields, and color interpretation (to exclude color blindness) in a variety of circumstances. The physician also assesses the retina, the optic nerve and its coverings, the lens, and the cornea. The extrinsic muscles are supplied by the abducent nerve [VI], the trochlear nerve [IV], and the oculomotor nerve [III]. The extrinsic muscles work synergistically to provide appropriate and conjugate eye movement: lateral rectus—abducent nerve [VI], superior oblique—trochlear nerve [IV], and remainder—oculomotor nerve [III]. The eye may be affected in systemic diseases. Diabetes mellitus typically affects the eye and may cause cataracts, macular disease, and retinal hemorrhage, all impairing vision. Occasionally unilateral paralysis of the extra-ocular muscles occurs and is due to brainstem injury or direct nerve injury, which may be associated with tumor compression or trauma. The paralysis of a muscle is easily demonstrated when the patient attempts to move the eye in the direction associated with normal action of that muscle. Typically the patient complains of double vision (diplopia). Loss of innervation of the muscles around the eye Loss of innervation of the orbicularis oculi by the facial nerve [VII] causes an inability to close the eyelids tightly, allowing the lower eyelid to droop away causing spillage of tears. This loss of tears allows drying of the conjunctiva, which may ulcerate, so allowing secondary infection. Loss of innervation of the levator palpebrae superioris by oculomotor nerve [III] damage causes an inability of the superior eyelid to elevate, producing a complete ptosis. Usually, oculomotor nerve [III] damage is caused by severe head injury. Loss of innervation of the superior tarsal muscle by sympathetic fibers causes a constant partial ptosis. Any lesion along the sympathetic trunk can induce this. An apical pulmonary malignancy should always be suspected because the ptosis may be part of Horner’s syndrome (see “In the clinic” on p. 920). In the clinic The “H-test” A simple “formula” for remembering the nerves that innervate the extraocular muscles is “LR6SO4 and all the rest are 3” (lateral rectus [VI], superior oblique [IV], all the rest including levator palpebrae superioris are [III]). The function of all extrinsic muscles and their nerves [III, IV, VI] that move the eyeball in both orbits can all easily be tested at the same time by having the patient track, without moving his or her head, an object such as the tip of a pen or a finger moved in an “H” pattern—starting from the midline between the two eyes (Fig. 8.98). In the clinic

Intraocular pressure will rise if the normal cycle of aqueous humor fluid production and absorption is disturbed so that the amount of fluid increases. This condition is glaucoma and can lead to a variety of visual problems including blindness, which results from compression of the retina and its blood supply. In the clinic With increasing age and in certain disease states the lens of the eye becomes opaque. Increasing opacity results in increasing visual impairment. A common operation is excision of the cloudy lens and replacement with a new man-made lens. In the clinic Direct visualization of the postremal (vitreous) chamber of the eye is possible in most clinical settings. It is achieved using an ophthalmoscope, which is a small battery-operated light with a tiny lens that allows direct visualization of the postremal (vitreous) chamber and the posterior wall of the eye through the pupil and the lens. It is sometimes necessary to place a drug directly onto the eye to dilate the pupil for better visualization. The optic nerve, observed as the optic disc, is easily seen. The typical four branches of the central retinal artery and the fovea are also seen. Using ophthalmoscopy the physician can look for diseases of the optic nerve, vascular abnormalities, and changes within the retina (Fig. 8.109). In the clinic High-definition optical coherence tomography (HD-OCT) (Fig. 8.111) is a procedure used to obtain subsurface images of translucent or opaque materials. It is similar to ultrasound, except that it uses light instead of sound to produce high-resolution cross-sectional images. It is especially useful in the diagnosis and management of optic nerve and retinal diseases. An epiretinal membrane (Fig. 8.112) is a thin sheet of fibrous tissue that develops on the surface of the retina in the area of the macula and can cause visual problems. If the visual problems are significant, surgical removal of the membrane may be necessary. In the clinic The eustachian tube links the middle ear and pharynx and balances the pressure between the outer and middle ear. Colds and allergies, particularly in children, can result in swelling of the lining of the eustachian tube, which can then impair normal drainage of fluid from the middle ear. The fluid then builds up behind the tympanic membrane, providing an attractive environment for bacteria and viruses to grow and cause otitis media. Left untreated, otitis media can lead to perforation of the tympanic membrane, hearing loss, meningitis, and brain abscess. In the clinic Examination of the ear The ear comprises three components—the external, middle, and internal ear. Clinical examination is carried out to assess hearing and balance. Further examination involves use of an otoscope or other imaging techniques. The external ear is easily examined. The external acoustic meatus and the tympanic membrane require otoscopic examination (Fig. 8.118B). An otoscope is a device through which light can be shone and the image magnified to inspect the external acoustic meatus and the tympanic membrane. The examination begins by grasping the posterosuperior aspect of the ear and gently retracting it to straighten the external auditory meatus. The normal tympanic membrane is relatively translucent and has a gray–reddish tinge. The handle of the malleus is visible near the center of the membrane. In the 5 o’clock position a cone of light is always demonstrated. The middle ear is investigated by CT and MRI to visualize the malleus, incus, and stapes. The relationship of these bones to the middle ear cavity is determined and any masses identified. The inner ear is also assessed by CT and MRI. In the clinic Swimmer’s ear, often called otitis externa, is a painful condition resulting from an infection in the external acoustic meatus. It frequently occurs in swimmers. In the clinic

Surfer’s ear, which is prevalent among individuals who surf or swim in cold water, results from the development of a “bony lump” in the external acoustic meatus. Growth of the lump eventually constricts the meatus and reduces hearing in the affected ear. In the clinic Although perforation of the tympanic membrane (eardrum) has many causes, trauma and infection are the most common. Ruptures of the tympanic membrane tend to heal spontaneously, but surgical intervention may be necessary if the rupture is large. Occasionally, it may be necessary to enter the middle ear through the tympanic membrane. Because the chorda tympani runs in the upper one-third of the tympanic membrane, incisions are always below this level. The richer blood supply to the posterior aspect of the tympanic membrane determines the standard surgical approach in the posteroinferior aspect. Otitis media (infection of the middle ear) is common and can lead to perforation of the tympanic membrane. The infection can usually be treated with antibiotics. If the infection persists, the chronic inflammatory change may damage the ossicular chain and other structures within the middle ear to produce deafness. In the clinic Infection within the mastoid antrum and mastoid cells is usually secondary to infection in the middle ear. The mastoid cells provide an excellent culture medium for infection. Infection of the bone (osteomyelitis) may also develop, spreading into the middle cranial fossa. Drainage of the pus within the mastoid air cells is necessary and there are numerous approaches for doing this. When undertaking this type of surgery, it is extremely important that care is taken not to damage the mastoid wall of the middle ear to prevent injury to the facial nerve [VII]. Any breach of the inner table of the cranial vault may allow bacteria to enter the cranial cavity and meningitis will ensue. In the clinic A lingual nerve injury proximal to where the chorda tympani joins it in the infratemporal fossa will produce loss of general sensation from the anterior two-thirds of the tongue, oral mucosa, gingivae, the lower lip, and the chin. If a lingual nerve lesion is distal to the site where it is joined by the chorda tympani, secretion from the salivary glands below the oral fissure and taste from the anterior two-thirds of the tongue will also be lost. In the clinic Anesthesia of the inferior alveolar nerve is widely practiced by most dentists. The inferior alveolar nerve is one of the largest branches of the mandibular nerve [V3], carries the sensory branches from the teeth and mandible, and receives sensory information from the skin over most of the mandible. The inferior alveolar nerve passes into the mandibular canal, courses through the body of the mandible, and eventually emerges through the mental foramen into the chin. of the inferior alveolar nerve by local anesthetic. To anesthetize this nerve the needle is placed lateral to the anterior arch of the fauces (palatoglossal arch) in the oral cavity and is advanced along the medial border around the inferior third of the ramus of the mandible so that anesthetic can be deposited in this region. It is also possible to anesthetize the infra-orbital and buccal nerves, depending on where the anesthesia is needed. In the clinic In most instances, access to peripheral veins of the arm and the leg will suffice for administering intravenous drugs and fluids and for obtaining blood for analysis; however, in certain circumstances it is necessary to place larger-bore catheters in the central veins, for example, for dialysis, parenteral nutrition, or the administration of drugs that have a tendency to produce phlebitis.

“Blind puncture” of the subclavian and jugular veins to obtain central venous access used to be standard practice. However, subclavian vein puncture is not without complications. As the subclavian vein passes inferiorly, posterior to the clavicle, it passes over the apex of the lung. Any misplacement of a needle into or through this structure may puncture the apical pleura, producing a pneumothorax. Inadvertent arterial puncture and vein laceration may also produce a hemopneumothorax. A puncture of the internal jugular vein (Fig. 8.165) carries fewer risks, but local hematoma and damage to the carotid artery are again important complications. Current practice is to identify major vessels using ultrasound and to obtain central venous access under direct vision to avoid any significant complication. In the clinic The jugular venous pulse is an important clinical sign that enables the physician to assess the venous pressure and waveform and is a reflection of the functioning of the right side of the heart. In the clinic The thyroid gland develops from a small region of tissue near the base of the tongue. This tissue descends as the thyroglossal duct from the foramen cecum in the posterior aspect of the tongue to pass adjacent to the anterior aspect of the middle of the hyoid bone. The thyroid tissue continues to migrate inferiorly and eventually comes to rest at the anterior aspect of the trachea in the root of the neck. Consequently, the migration of thyroid tissue may be arrested anywhere along the embryological descent of the gland. Ectopic thyroid tissue is relatively rare. More frequently seen is the cystic change that arises from the thyroglossal duct. The usual symptom of a thyroglossal duct cyst is a midline mass. Ultrasound easily demonstrates its nature and position, and treatment is by surgical excision. The whole of the duct as well as a small part of the anterior aspect of the hyoid bone must be excised to prevent recurrence. In the clinic A thyroidectomy is a common surgical procedure. In most cases it involves excision of part or most of the thyroid gland. This surgical procedure is usually carried out for benign diseases, such as multinodular goiter and thyroid cancer. Given the location of the thyroid gland, there is a possibility of damaging other structures when carrying out a thyroidectomy, namely the parathyroid glands and the recurrent laryngeal nerve (Fig. 8.181). Assessment of the vocal folds is necessary before and after thyroid surgery because the recurrent laryngeal nerves are closely related to ligaments that bind the gland to the larynx and can be easily traumatized during surgical procedures. In the clinic Thyroid gland pathology is extremely complex. In essence, thyroid gland pathology should be assessed from two points of view. First, the thyroid gland may be diffusely or focally enlarged, for which there are numerous causes. Second, the thyroid gland may undersecrete or oversecrete the hormone thyroxine. One of the commonest disorders of the thyroid gland is a multinodular goiter, which is a diffuse irregular enlargement of the thyroid gland with areas of thyroid hypertrophy and colloid cyst formation. Most patients are euthyroid (i.e., have normal serum thyroxine levels). The typical symptom is a diffuse mass in the neck, which may be managed medically or may need surgical excision if the mass is large enough to affect the patient’s life or cause respiratory problems. Isolated nodules in the thyroid gland may be a dominant nodule in a multinodular gland or possibly an isolated tumor of the thyroid gland. Isolated tumors may or may not secrete thyroxine depending on their cellular morphology. Treatment is usually by excision.

Immunological diseases may affect the thyroid gland and may overstimulate it to produce excessive thyroxine. These diseases may be associated with other extrathyroid manifestations, which include exophthalmos, pretibial myxedema, and nail changes. Other causes of diffuse thyroid stimulation include viral thyroiditis. Some diseases may cause atrophy of the thyroid gland, leading to undersecretion of thyroxine (myxedema). In the clinic The parathyroid glands develop from the third and fourth pharyngeal pouches and translocate to their more adult locations during development. The position of the glands can be highly variable, sometimes being situated high in the neck or in the thorax. Tumors develop in any of these locations (Fig. 8.182). In the clinic Damage to either the right or left recurrent laryngeal nerve may lead initially to a hoarse voice and finally to an inability to speak. Recurrent laryngeal nerve palsy can occur from disruption of the nerves anywhere along their course. Furthermore, interruption of the vagus nerves before the division of the recurrent laryngeal nerves can also produce vocal symptoms. Lung cancer in the apex of the right lung can affect the right recurrent laryngeal nerve, whereas cancers that infiltrate into the area between the pulmonary artery and aorta, an area known clinically as the “aortopulmonary window,” can affect the left recurrent laryngeal nerve. Thyroid surgery also can traumatize the recurrent laryngeal nerves. In the clinic Clinical lymphatic drainage of the head and neck Enlargement of the neck lymph nodes (cervical lymphadenopathy) is a common manifestation of disease processes that occur in the head and neck. It is also a common manifestation of diffuse diseases of the body, which include lymphoma, sarcoidosis, and certain types of viral infection such as glandular fever and human immunodeficiency virus (HIV) infection. Evaluation of cervical lymph nodes is extremely important in determining the nature and etiology of the primary disease process that has produced nodal enlargement. Clinical evaluation includes a general health assessment, particularly relating to symptoms from the head and neck. Examination of the nodes themselves often gives the clinician a clue as to the nature of the pathological process. Soft, tender, and inflamed lymph nodes suggest an acute inflammatory process, which is most likely to be infective. Firm multinodular large-volume rubbery nodes often suggest a diagnosis of lymphoma. Examination should also include careful assessment of other nodal regions, including the supraclavicular fossae, the axillae, the retroperitoneum, and the inguinal regions. Further examination may include digestive tract endoscopy, chest radiography, and body CT scanning. Most cervical lymph nodes are easily palpable and suitable for biopsy to establish a tissue diagnosis. Biopsy can be performed using ultrasound for guidance and good samples of lymph nodes may be obtained. The lymphatic drainage of the neck is somewhat complex, clinically. A relatively simple “level” system of nodal enlargement has been designed that is extremely helpful in evaluating lymph node spread of primary head and neck tumors. Once the number of levels of nodes are determined, and the size of the lymph nodes, the best mode of treatment can be instituted. This may include surgery, radiotherapy, and chemotherapy. The lymph node level also enables a prognosis to be made. The levels are as follows (Fig. 8.199): Level I—from the midline of the submental triangle up to the level of the submandibular gland. Level II—from the skull base to the level of the hyoid bone anteriorly from the posterior border of the sternocleidomastoid muscle. Level III—the inferior aspect of the hyoid bone to the bottom cricoid arch and anterior to the posterior border of the sternocleidomastoid up to the midline.

Level IV—from the inferior aspect of the cricoid to the top of the manubrium of the sternum and anterior to the posterior border of the sternocleidomastoid muscle. Level V—posterior to the sternocleidomastoid muscle and anterior to the trapezius muscle above the level of the clavicle. Level VI—below the hyoid bone and above the jugular (sternal) notch in the midline. Level VII—below the level of the jugular (sternal) notch. In the clinic In emergency situations, when the airway is blocked above the level of the vocal folds, the median cricothyroid ligament can be perforated and a small tube inserted through the incision to establish an airway. Except for small vessels and the occasional presence of a pyramidal lobe of the thyroid gland, normally there are few structures between the median cricothyroid ligament and the skin. In the clinic A tracheostomy is a surgical procedure in which a hole is made in the trachea and a tube is inserted to enable ventilation. A tracheostomy is typically performed when there is obstruction to the larynx as a result of inhalation of a foreign body, severe edema secondary to anaphylactic reaction, or severe head and neck trauma. The typical situation in which a tracheostomy is performed is in the calm atmosphere of an operating theater. A small transverse incision is placed in the lower third of the neck anteriorly. The strap muscles are deviated laterally and the trachea can be easily visualized. Occasionally it is necessary to divide the isthmus of the thyroid gland. An incision is made in the second and third tracheal rings and a small tracheostomy tube inserted. After the tracheostomy has been in situ for the required length of time, it is simply removed. The hole through which it was inserted almost inevitably closes without any intervention. Patients with long-term tracheostomies are unable to vocalize because no air is passing through the vocal cords. In the clinic Laryngoscopy is a medical procedure that is used to inspect the larynx. The functions of laryngoscopy include the evaluation of patients with difficulty swallowing, assessment of the vocal cords, and assessment of the larynx for tumors, masses, and weak voice. The larynx is typically visualized using two methods. Indirect laryngoscopy involves passage of a small rod-mounted mirror (not dissimilar to a dental mirror) into the oropharynx permitting indirect visualization of the larynx. Direct laryngoscopy can be performed using a device with a curved metal tip that holds the tongue and epiglottis forward, allowing direct inspection of the larynx. This procedure can be performed only in the unconscious patient or in a patient in whom the gag reflex is not intact. Other methods of inspection include the passage of fiberoptic endoscopes through either the oral cavity or nasal cavity. In the clinic The nasal septum is typically situated in the midline; however, septal deviation to one side or the other is not uncommon, and in many cases is secondary to direct trauma. Extreme septal deviation can produce nasal occlusion. The deviation can be corrected surgically. In the clinic Most cancers of the oral cavity, oropharynx, nasopharynx, larynx, sinuses, and salivary glands arise from the epithelial cells that line them, resulting in squamous cell carcinoma. The majority of these are related to cell damage caused by smoking and alcohol use. Certain viruses are also related to cancers in the head and neck, including human papillomavirus (HPV) and Epstein-Barr virus (EBV). A 50-year-old overweight woman came to the doctor complaining of hoarseness of voice and noisy breathing. She was also concerned at the increase in size of her neck. On examination she had a slow pulse rate (45 beats per minute). She also had an irregular knobby mass in the anterior aspect of the lower neck, which deviated the trachea to the right. A clinical diagnosis of a multinodular goiter and hypothyroidism was made.

Enlargement of the thyroid gland is due to increased secretion of thyroid-stimulating hormone, which is usually secondary to diminished output of thyroid hormones. The thyroid undergoes periods of activity and regression, which can lead to the formation of nodules, some of which are solid and some of which are partially cystic (colloid cysts). This nodule formation is compounded by areas of fibrosis within the gland. Other causes of multinodular goiter include iodine deficiency and in certain circumstances, drugs that interfere with the metabolism and production of thyroxine. The typical symptom of a goiter is a painless swelling of the thyroid gland. It may be smooth or nodular, and occasionally it may extend into the superior mediastinum as a retrosternal goiter. The trachea was deviated. The enlargement of the thyroid gland due to a multinodular goiter may not be symmetrical. In this case there was significant asymmetrical enlargement of the left lobe of the thyroid deviating the trachea to the right. The patient had a hoarse voice and noisy breathing. If the thyroid gland enlargement is significant it can compress the trachea, narrowing it to such an extent that a “crowing sound” is heard during inspiration (stridor). Other possible causes for hoarseness include paralysis of the vocal cord due to compression of the left recurrent laryngeal nerve from the goiter. Of concern is the possibility of malignant change within the goiter directly invading the recurrent laryngeal nerve. Fortunately, malignant change is rare within the thyroid gland. When patients have a relatively low production of thyroxine such that the basal metabolic rate is reduced they become more susceptible to infection, including throat and upper respiratory tract infections. On examination the thyroid gland moved during swallowing. Characteristically, an enlarged thyroid gland is evident as a neck mass arising on one or both sides of the trachea. The enlarged thyroid gland moves on swallowing because it is attached to the larynx by the pretracheal fascia. The patient was hypothyroid. Hypothyroidism refers to the clinical and biochemical state in which the thyroid gland is underactive (hyperthyroidism refers to an overactive thyroid gland). Some patients have thyroid masses and no clinical or biochemical abnormalities—these patients are euthyroid. The hormone thyroxine controls the basal metabolic rate; therefore, low levels of thyroxine affect the resting pulse rate and may produce other changes, including weight gain, and in some cases depression. The patient was insistent upon surgery. After discussion about the risks and complications, a subtotal thyroidectomy was performed. After the procedure the patient complained of tingling in her hands and feet and around her mouth, and carpopedal spasm. These symptoms are typical of tetany and are caused by low serum calcium levels. The etiology of the low serum calcium level was trauma and bruising of the four parathyroid glands left in situ after the operation. Undoubtedly the trauma of removal of such a large thyroid gland produced a change within the parathyroid gland, which failed to function appropriately. The secretion of parathyroid hormone rapidly decreased over the next 24 hours, resulting in increased excitability of peripheral nerves, manifest by carpopedal spasm and orofacial tingling. Muscle spasms can also be elicited by tapping the facial nerve [VII] as it emerges from the parotid gland to produce twitching of the facial muscles (Chvostek’s sign). The patient recovered from these symptoms due to a low calcium level over the next 24 hours. At her return to the clinic the patient was placed on supplementary oral thyroxine, which is necessary after removal of the thyroid gland. The patient also complained of a hoarse voice. The etiology of her hoarse voice was damage to the recurrent laryngeal nerve.

The recurrent laryngeal nerve lies close to the thyroid gland. It may be damaged in difficult surgical procedures, and this may produce unilateral spasm of the ipsilateral vocal cord to produce a hoarse voice. Since the thyroidectomy and institution of thyroxine treatment, the patient has lost weight and has no further complaints. A 33-year-old man was playing cricket for his local Sunday team. As the new bowler pitched the ball short, it bounced higher than he anticipated and hit him on the side of his head. He immediately fell to the ground unconscious, but after about 30 seconds he was helped to his feet and felt otherwise well. It was noted he had some bruising around his temple. He decided not to continue playing and went to watch the match from the side. Over the next hour he became extremely sleepy and was eventually unrousable. He was rushed to hospital. When he was admitted to hospital, the patient’s breathing was shallow and irregular and it was necessary to intubate him. A skull radiograph demonstrated a fracture in the region of the pterion. No other abnormality was demonstrated other than minor soft tissue bruising over the left temporal fossa. A CT scan was performed. The CT scan demonstrated a lentiform area of high density within the left cranial fossa. A diagnosis of extradural hemorrhage was made. Fractures in the region of the pterion are extremely dangerous. A division of the middle meningeal artery passes deep to this structure and is subject to laceration and disruption, especially in conjunction with a skull injury in this region. In this case the middle meningeal artery was torn and started to bleed, producing a large extradural clot. The patient’s blood pressure began to increase. Within the skull there is a fixed volume and clearly what goes in must come out (e.g., blood, cerebrospinal fluid). If there is a space-occupying lesion, such as an extradural hematoma, there is no space into which it can decompress. As the lesion expands, the brain becomes compressed and the intracranial pressure increases. This pressure compresses vessels, so lowering the cerebral perfusion pressure. To combat this the homeostatic mechanisms of the body increase the blood pressure to overcome the increase in intracerebral pressure. Unfortunately, the increase in intracranial pressure is compounded by the cerebral edema that occurs at and after the initial insult. An urgent surgical procedure was performed. Burr holes were placed around the region of the hematoma and it was evacuated. The small branch of the middle meningeal artery was ligated and the patient spent a few days in the intensive care unit. Fortunately the patient made an uneventful recovery. A 35-year-old man was involved in a fight and sustained a punch to the right orbit. He came to the emergency department with double vision. The double vision was only in one plane. Examination of the orbits revealed that when the patient was asked to look upward the right eye was unable to move superiorly when adducted. There was some limitation in general eye movement. Assessment of the lateral rectus muscle (abducent nerve [VI]), superior oblique muscle (trochlear nerve [IV]), and the rest of the eye muscles (oculomotor nerve [III]) was otherwise unremarkable. The patient underwent a CT scan. A CT scan of the facial bones demonstrated a fracture through the floor of the orbit (Fig. 8.293). A careful review of this CT scan demonstrated that the inferior oblique muscle had been pulled inferiorly with the fragment of bone in the fracture. This produced a tethering effect, so when the patient was asked to gaze in the upward direction, the left eye was able to do so but the right eye was unable to because of the tethered inferior oblique muscle. The patient underwent surgical exploration to elevate the small bony fragment and return the inferior oblique to its appropriate position. On follow-up the patient had no complications.

A 25-year-old man complained of significant swelling in front of his right ear before and around mealtimes. This swelling was associated with considerable pain, which was provoked by the ingestion of lemon sweets. On examination he had tenderness around the right parotid region and a hard nodule was demonstrated in the buccal mucosa adjacent to the right upper molar teeth. A diagnosis of parotid duct calculus was made. The formation of stones in the salivary glands is not uncommon, but it is more likely in the submandibular gland than in the parotid gland because the saliva is more mucinous and the duct has a long upward course from the floor of the mouth. Nevertheless, stones do form in the parotid gland and the parotid ducts. Notably, most parotid duct calculi and submandibular duct calculi occur in mouths with excellent dental hygiene and mucosa. An ultrasound scan was performed. An initial ultrasound scan demonstrated a stone in the distal end of the right parotid duct with evidence of ductal dilation (eFig. 8.294). Assessment of the gland also demonstrated dilated ducts within the gland and evidence of intraparotid lymphadenopathy. The patient was treated with antibiotics. A course of antibiotics was given to remove the bacteria that had produced the inflammation. On return to the doctor some days later the gland was normal in size and there was no evidence of inflammation or infection. An operation was necessary. The stone was at the distal end of the parotid duct and it would seem logical and straightforward to make a small incision at the sphincter in the buccal mucosa and deliver the stone, thus permitting the gland to drain normally. Unfortunately, in this patient’s case the gland was significantly destroyed by the chronic obstruction and bacterial infection. Furthermore, smaller calculi were also demonstrated in the gland at ultrasound. On direct questioning it appeared that the patient had had numerous attacks over the previous 4–5 years and it was decided that the parotid gland should be removed surgically. The patient consented for removal of the parotid gland and a discussion of the possibility for loss of facial function and facial paralysis was had with the patient at this time. Within the parotid gland the facial nerve [VII] divides into its five terminal branches. At operation the gland is displayed and extremely careful dissection is necessary to peel away the parotid gland from the branches of the facial nerve [VII]. This procedure was made more difficult by the chronic inflammatory change within the gland. After the procedure the patient made a good recovery, though there was some mild paralysis of the whole of the right side of the face. Importantly, taste to the anterior two-thirds of the tongue was preserved. The taste fibers to the anterior two-thirds of the tongue travel in the chorda tympani nerve, which is a branch of the facial nerve [VII]. This nerve leaves the facial nerve [VII] to join the lingual nerve proximal to the parotid gland; therefore, any damage to the facial nerve [VII] within the parotid gland does not affect special sensation (taste). Over the following week the paralysis improved and was likely due to nerve bruising during the procedure. The patient remained asymptomatic. A 60-year-old woman was brought to the emergency department with acute right-sided weakness, predominantly in the upper limb, which lasted for 24 hours. She made an uneventful recovery, but was extremely concerned about the nature of her illness and went to see her local doctor. A diagnosis of a transient ischemic attack (TIA) was made. A TIA is a neurological deficit resolving within 24 hours. It is a type of stroke. Neurological deficits may be permanent or transient. Most transient events resolve within 21 days; any failure of resolution beyond 21 days is an established stroke. An investigation into the cause of the TIA was undertaken.

Eighty-five percent of all strokes result from cerebral infarction, of which most are due to embolization. A duplex Doppler scan of the carotid vessels was performed. The majority of emboli originate from plaques that develop at and around the carotid bifurcation. Emboli consist of platelet aggregates, cholesterol, and atheromatous debris. Emboli may also arise from the heart secondary to cardiac tumors or myocardial infarction. The lesion in the brain was on the left side. The motor cortex for the whole of the right side of the body is represented in the left motor strip of the brain, which sits on the precentral gyrus. The duplex Doppler ultrasound scan demonstrated a significant narrowing (stenosis) of the left internal carotid artery with evidence of plaque formation and abnormal flow in this region. The narrowing was approximately 90%. Treatment required an operation. A carotid endarterectomy (removal of the stenosis and the atheromatous plaque) was planned. This procedure is indicated in the presence of an ulcerating plaque with stenosis. The procedure was carried out under general anesthetic and a curvilinear incision was placed in the left side of the neck. The common carotid, external carotid, and internal carotid arteries were displayed. All vessels were clamped and a shunt was placed from the common carotid artery into the internal carotid artery to maintain cerebral blood flow during the procedure. The internal carotid artery was opened and the plaque excised. After the procedure the patient did extremely well and suffered no further cerebral events. However, a new medical student examined the patient the following day and demonstrated a number of interesting findings. These included altered skin sensation inferior to the left mandible, altered sensation on the left side of the soft palate, a paralyzed left vocal cord, inability to shrug the left shoulder, and a tongue that deviated to the left. The etiology of these injuries was due to localized nerve trauma. This constellation of neurological deficits can be accounted for by trauma to the nerves that are close to the carotid bifurcation. The changes in skin sensation can be accounted for by a neurapraxia due to damage to cervical nerves. The alteration in sensation in the soft palate is due to neurapraxia of the glossopharyngeal nerve [IX]. The paralyzed left cord results from neurapraxia of the recurrent laryngeal nerve, while the inability to shrug the shoulder is due to neurapraxia of the accessory nerve [XI]. Deviation of the tongue can be accounted for by damage to the hypoglossal nerve [XII]. Most of these changes are transient and are usually due to traction injuries during the surgical procedure. A 33-year-old fit and well woman came to the emergency department complaining of double vision and pain behind her right eye. She had no other symptoms. On examination of the right eye the pupil was dilated. There was a mild ptosis. Testing of eye movement revealed that the eye turned down and out and the pupillary reflex was not present. These findings revealed that the patient had an ipsilateral third nerve palsy (palsy of the oculomotor nerve [III]). The oculomotor nerve [III] is the main motor nerve to the ocular and extra-ocular muscles. It arises from the midbrain and pierces the dura mater to run in the lateral wall of the cavernous sinus. The oculomotor nerve [III] leaves the cranial cavity and enters the orbit through the superior orbital fissure. Within this fissure it divides into its superior and inferior divisions. The site of the nerve lesion needs to be assessed. Third nerve palsy may involve the nucleus of the oculomotor nerve [III], which typically spares the pupil and is painless. The pupillary reflexes are supplied from the autonomic fibers of the Edinger–Westphal nucleus, which pass through the ciliary ganglion.

The lesion cannot be a primary oculomotor nerve [III] nuclear injury. As both the pupillary reflexes and vision are affected, the lesion is likely to be along the course of the oculomotor nerve [III]. Medical conditions such as diabetes mellitus and vascular disease may produce an isolated oculomotor nerve [III] injury, but they are not associated with pain. The lesion was caused by an aneurysm. One of the commonest causes of a third nerve palsy is pressure on the nerve from a posterior communicating artery aneurysm, which lies parallel to the nerve on the anterior aspect of the brainstem. As the aneurysm abuts the outside of the oculomotor nerve [III], it involves the parasympathetic fibers, which lead to a predominance of the loss of pupillary function over general function. The aneurysm was imaged with an angiogram. The patient initially underwent CT and MRI scanning. Currently, the definitive test for assessment of aneurysms arising from the circle of Willis and its branches is a digital subtraction angiogram. The angiogram demonstrated the posterior communicating artery aneurysm. The patient underwent surgery and made an excellent recovery. A 10-year-old boy was brought to an ENT surgeon (ear, nose, and throat surgeon) with epistaxis (nose bleeding). The bleeding was associated with his nose picking habit. However, the bleeding was profuse and on two occasions required hospital admission and nasal packing. On inspection an indurated area was noted. The typical findings are an indurated area in the anterior inferior aspect of the nasal septum (Kiesselbach’s area). This is a very vascular area that has a considerable number of veins, which are often traumatized during nose picking. The patient underwent treatment. Typical treatment is cauterization of these prominent veins in Kiesselbach’s area, which is usually performed by a simple local analgesia and the application of silver nitrate. Unfortunately, the boy was involved in a fight the next day and again developed severe epistaxis, which again was difficult to control. Not only is there a rich venous plexus around Kiesselbach’s area, but there is also a significant arterial supply, which is provided from the nasal septal branches of the posterior and anterior ethmoidal arteries and the branches of the greater palatine artery. These are supplemented from the septal branches of the superior labial artery. In most cases treatment is conservative. Conservative treatment usually involves packing the nasal cavity until bleeding has stopped and correcting any bleeding abnormality. In patients with bleeding refractory to medical treatment a series of maneuvers have been employed, including ligating the anterior and posterior ethmoidal arteries through a medial incision in the canthus orbit, or by ligating other major arteries supplying the nasal cavity. Unfortunately, many of these procedures fail because of the rich and diverse origin of blood supply to the nasal cavity. Determination of the specific site of bleeding can be achieved radiologically. By placing a catheter from the femoral artery through the aorta and into the carotid circulation the sphenopalatine artery can be easily cannulated from the maxillary branch of the external carotid artery. Bleeding can usually be demonstrated and the vessel can be embolized using small particles. Fortunately in this young boy’s case, bleeding stopped after further medical management and he remained asymptomatic. A 30-year-old woman came to her doctor with a history of amenorrhea (absence of menses) and galactorrhea (the production of breast milk). She was not pregnant and appeared otherwise fit and well. Serum prolactin was measured. Prolactin is a hormone produced by the pituitary gland and necessary for the production of breast milk postpartum. This hormone was markedly elevated. Further clinical tests demonstrated visual field defects. The patient went to see an optometrist who performed a visual field assessment and demonstrated a reduction in the lateral aspects of the normal visual fields. This was bilateral and symmetrical—a bilateral temporal hemianopia.

The visual pathways have now determined the site of the lesion. Visual information from the temporal fields is projected onto the medial aspect of the retina bilaterally. The visual information from the medial aspects of the retina is carried in fibers that cross the midline through the optic chiasm to the opposite side. The lesion is in the area of the optic chiasm. Any disruption of the optic chiasm produces the field defect of bitemporal hemianopia. Tumors of the optic chiasm are unusual, though gliomas do occur. More frequently, compression of the optic chiasm by tumors in the vicinity is the usual cause for bitemporal hemianopia. A pituitary tumor was diagnosed. The optic chiasm is anterior and extremely close to the pituitary gland. Given that the patient is producing excessive amounts of prolactin (a pituitary tumor) and there is loss of the function of the chiasm, the most likely clinical explanation is an exophytic pituitary tumor compressing the optic chiasm. An MRI scan was performed and demonstrated a large tumor (macroadenoma) of the pituitary gland. Drug treatment was commenced and the tumor shrank (eFig. 8.295). The endocrinological effects of the prolactin secretion also stopped. Follow-up scans were performed. Over the ensuing few years the tumor shrank. Unfortunately, the patient again began to secrete prolactin and surgery was performed. A transsphenoidal approach was undertaken. With meticulous accuracy a series of very fine instruments was passed through the nasal cavity into the sphenoid bone. The bone was drilled and via this approach the pituitary gland was removed. Extreme care must be taken because on both sides of the pituitary gland is the cavernous sinus through which the internal carotid artery, oculomotor nerve [III], trochlear nerve [IV], trigeminal nerve [V], and abducent nerve [VI] pass. 1121.e2 1121.e1 Fig. 8.7, cont’d Skull. Conceptual Overview • Relationship to Other Regions Fig. 8.16, cont’d In the clinic—cont’d In the clinic—cont’d In the clinic—cont’d In the clinic—cont’d In the clinic—cont’d Table 8.5 Cranial nerves (see Table 8.4 for abbreviations)—cont’d In the clinic—cont’d Table 8.7 Muscles of the face—cont’d In the clinic—cont’d In the clinic—cont’d Fig. 8.149, cont’d In the clinic—cont’d Fig. 8.235, cont’d Fig. 8.239, cont’d Surface Anatomy • Visualizing Structures at the CIII/CIV and CVI Vertebral Levels Surface Anatomy • How to Locate the Cricothyroid Ligament Surface Anatomy • Major Features of the Face Neuroanatomy and neuroscience are fields of science that seek to explain embryonic development, structural organization, and physiological function of the nervous system. Both fields work together to help identify the simple to the most complex questions of human sensory, motor, behavioral, and higher cognitive functions. The focus of this chapter is to introduce the basic structures and functions of the individual and systemic components of the human nervous system. Part I: Nervous system Organization of the human nervous system is structurally divided into the central nervous system (CNS) and peripheral nervous system (PNS) (eFig. 9.1). Components of the CNS are the brain and spinal cord, which are enclosed within the cranial cavity and vertebral column of the axial skeleton. Peripheral nervous system structures include cranial nerves, spinal nerves, autonomic nerves, and the enteric nervous system.

During the third week of development the outermost layer of the embryo—the ectoderm—thickens to form a neural plate (eFig. 9.2A). This plate develops a longitudinally running neural groove, which deepens so that it is flanked on either side by neural folds (eFig. 9.2B). These folds further develop and eventually fuse during a process called neurulation to form a long tubelike structure called the neural tube with an inner lumen called the neural canal (eFig. 9.3). Fusion of the tube starts at the midpoint and extends cranially and caudally so that the tube is fully formed by the fourth week. Continued proliferation of the cells at the cephalic end cause the neural tube to dilate and form the three primary brain vesicles (eFig. 9.4): the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain), which later give rise to the structures of the brain. Caudally, the neural tube lengthens and narrows to form the spinal cord. The neural canal forms the cavities of the ventricular system in the brain and central canal of the spinal cord (eTable 9.1). The peripheral nervous system consists of cranial nerves, spinal nerves, spinal ganglia, the enteric system, and autonomic ganglia. The peripheral nervous system is formed by nerve fibers that extend out of the central nervous system and by neurons and their fibers that develop from migratory neural crest cells (eFig. 9.4A). Like the neural tube, neural crest cells originate from surface ectoderm and initially lie on each side of the developing CNS. Several terms are used to identify the orientation and location of neural structures. The orientation nomenclature is quite simple in organisms such as fish and reptiles, which have a linear nervous system. For these animals, ventral (Latin for “belly”) is oriented toward the ground, dorsal (Latin for “back”) toward the sky, rostral (Latin for “beak”) toward the snout, and caudal (Latin for “tail) toward the tail (eFig. 9.5). Because humans are bipedal and maintain an erect posture, the nervous system makes an obligatory bend of 80 to 90 degrees at the midbrain–diencephalic junction. Because of this, directional references such as ventral, dorsal, rostral, and caudal have different meanings along different locations of the CNS structures (eFig. 9.6A). An additional set of terms that remain constant in their reference to orientation of nervous system structures are anterior, posterior, superior, and inferior. When studied through imaging or in histopathology, the nervous system is observed in sections cut from one of three different planes: a coronal plane, which divides the nervous system into anterior and posterior parts; the sagittal plane, which is oriented at a right angle to the coronal plane and divides the nervous system into left and right parts; and a horizontal (also referred to as axial or transverse) plane, which divides the nervous system into superior and inferior parts (eFig. 9.6). Note that a sagittal plane passing through the midline may also be referred to as a midsagittal section, whereas a section taken just lateral to the midline is referred to as a parasagittal section. Nerve cells (neurons) and glial cells are the primary cellular components of the nervous system. Neurochemical signaling is predominantly carried out through a complex series of physiological connections between adjoining neurons. Glial cells participate in a constellation of functions that are vital for proper brain function. Their historically appreciated contribution to neuronal function has expanded to include recognition of their role in regulating the content of the extracellular space and regulation of neurotransmitters at the synaptic junction.

Neurons consist of a cell body (or soma), which contains the cell nucleus, short processes called dendrites for receiving input from other neurons, and long processes called axons, which conduct signals away from the cell body (eTable 9.2). Depending on their location, neuronal morphology can be quite variable. The majority of mammalian neurons are multipolar, indicating that there are several dendrites from one end and a single axon that branches extensively at its terminus (eFig. 9.7). Some additional neuronal types are bipolar, unipolar, and pseudounipolar (eFig. 9.8). To prevent the loss of linear signal propagation, glial cells form a phospholipid-based layer of insulation called the myelin sheath along the length of the axon (eFig. 9.7). The myelin sheath is formed by oligodendrocytes in the CNS and Schwann cells in the PNS. Interspersed between the segments of myelin are exposed segments of the axon called nodes of Ranvier, which have a large population of voltage-gated ion channels. Presence of the ion channels facilitates rapid conduction of the action potential (a transient voltage change in the axonal membrane) from node to node in a process called saltatory conduction (eFig. 9.7). Functionally, the nervous system is organized into a somatic nervous system and visceral nervous system. The somatic nervous system consists of nerves that carry conscious sensation from peripheral regions back to the CNS and nerves that exit the CNS to innervate voluntary (skeletal) muscles. In contrast, the visceral nervous system consists of nerves that carry sensory information into and motor (autonomic) innervation out of the CNS to regulate homeostatic functions. Further discussion of the somatic and visceral nervous systems will be presented within the context of the subsequent “Spinal Cord” section. Part II: Brain Externally, the outer surface of the brain, or cerebral cortex, is composed of six layers of cell bodies referred to as gray matter. Internally, the myelinated axonal processes of these cells extend into the cerebral hemispheres. Because of the whitish appearance of these large bundles of myelinated axons, they are referred to as white matter. In the brain, gray matter is predominantly located on the cortical surface and the white matter runs deep inside the cerebral hemispheres; the opposite is true for the spinal cord, where the white matter is superficial to the gray matter. Topographically, the surface of the cerebral hemispheres has a series of elevations called gyri and infoldings referred to as sulci, both of which significantly increase the surface area of the brain. Structurally, each cerebral hemisphere is divided into four major anatomical lobes: frontal, parietal, occipital, and temporal (eFig. 9.9A). The frontal lobes are located anteriorly and are separated from the more posterior parietal lobe by the central sulcus (sulcus of Rolando) (eFig. 9.9A). Laterally, the frontal lobe is separated from the temporal lobe by the lateral sulcus (fissure of Sylvius). Although there is no specific demarcation between the parietal and occipital lobe laterally, along the medial aspect of the hemispheres the two lobes are separated by the parieto-occipital sulcus (eFig. 9.9B). Along the midline, the cerebral hemispheres are separated from one another by the longitudinal fissure (interhemispheric fissure, sagittal fissure). Concealing a small area of cortex called the insula laterally are portions of the frontal, parietal, and temporal lobes collectively referred to as the operculum (Latin for “lid”) (eFig. 9.10). The insula represents fusion of the telencephalon and diencephalon and can be seen by gently prying open the lateral sulcus.

The path to and from the cerebral cortex is achieved through various white matter pathways coursing through the spinal cord, brainstem, and cerebral hemispheres. Beneath the gray matter of the cortical surface is an expansion of white matter referred to as the corona radiata. This white matter pathway condenses to form the internal capsule, a V-shaped structure when viewed in horizontal sections that contains axons traversing to and from various cortical and deep nuclear structures (eFig. 9.11). The internal capsule is divided into three parts based on connections to different parts of the cortex and underlying structures. The most anterior portion of this white matter pathway is the anterior limb, which is bounded medially by the head of the caudate and laterally by the globus pallidus and putamen. The anterior limb transitions into the genu (Latin for “knee”) at the level of the interventricular foramen (of Monro) and completes its course as the posterior limb, situated lateral to the thalamus and medial to the globus pallidus and putamen. In addition to this more vertical stream of axonal connections is the horizontally running corpus callosum. The corpus callosum (eFig. 9.12) is formed by myelinated axons horizontally linking the two cerebral hemispheres to one another, and it is divided into a rostrum, genu, body, and splenium (eFig. 9.12). The ventricular system is derived from the inner lumen of the developing neural tube. As the brain continues to grow, the caverns and canals of the ventricular system adapt to the shape of the cerebral hemispheres, diencephalon, pons, medulla, and cerebellum, which form the surrounding walls (eFig. 9.13). Inferior and lateral to the corpus callosum are two large, fluid-filled cavities that represent the beginning of the ventricular system. These most rostral cavities are the two C-shaped lateral ventricles, located within the cerebral hemispheres (eFig. 9.14). As the lateral ventricles extend through all of the lobes of the cerebral hemispheres, they are divided into five named parts. In the frontal lobe is the anterior (frontal) horn, which transitions into the body within the frontal and parietal lobes (eFig. 9.15). Projecting into the occipital lobe is the posterior (occipital) horn (eFig. 9.15). A final horn extends inferiorly and anteriorly as the inferior (temporal) horn in the temporal lobe (eFig. 9.15). Near the splenium of the corpus callosum, the body, posterior, and inferior horns come together at the atrium/trigone of the lateral ventricles (eFig. 9.15). Lining most of the ventricles is the choroid plexus (eFig. 9.16), a series of modified ependymal cells responsible for producing 0.5 L of cerebrospinal fluid (CSF) a day in adults. From the lateral ventricles, CSF flows through the interventricular foramen (of Monro) to the slitlike third ventricle, which is surrounded by the thalamus and hypothalamus (eFig. 9.15). The third ventricle communicates with the fourth ventricle via the cerebral aqueduct (aqueduct of Sylvius), which courses through the midbrain (eFig. 9.15). Surrounded by the pons and medulla anteriorly and the cerebellum posteriorly, the fourth ventricle sends CSF out of the ventricular system and into the subarachnoid space via the lateral foramina of Luschka and midline foramen of Magendie (eFig. 9.15).

Within the bony encasement of the skull and vertebral column, the CNS is surrounded by three concentric, connective tissue coverings called meninges (from Greek word meninx for “membrane”), which act to support and stabilize the brain and spinal cord. The focus of this section will be on the cranial meninges. The spinal meninges, which have a slightly different configuration, will be discussed in the “Spinal Cord” section. The outermost covering is the dura (Latin for “hard”) mater (Latin for “mother”), a tough, fibrous sheet composed of two layers. The outer periosteal layer is adherent to the skull, and the inner meningeal layer lies against the underlying arachnoid mater (eFig. 9.17). Although these two layers are closely adherent to one another, they do separate in some regions to form dural venous sinuses, which receive cerebral venous drainage (eFig. 9.18). The anatomy of the venous sinuses will be discussed in the “Cerebral Vasculature” section. Two potential spaces exist as the epidural (extradural) space, superficial to the periosteal layer, and subdural space, deep to the meningeal dural layer. These spaces can become filled with blood during vascular trauma (eTable 9.3). Within the cranial cavity, the meningeal layer of dura mater folds in on itself in several areas to form dural reflections, or septa. These reflections are known as the falx (Latin for “sickle”) cerebri between the cerebral hemispheres, as the tentorium cerebelli between the cerebral hemispheres and cerebellum, and as the falx cerebelli between the cerebellar hemispheres (eFig. 9.17). A smaller reflection, the diaphragm sellae, covers the pituitary fossa and underlying pituitary gland. Deep to the dura mater is the arachnoid (from the Greek word arachne meaning “spider’s web”) mater. The outer layer of the arachnoid mater is composed of several layers of flattened cells that lie adjacent to the meningeal layer of the dura mater (eFig. 9.19). Strands of connective tissue extend from this outer layer to form arachnoid trabeculae, which connect internally to the pia mater (eFig. 9.19). The pia mater forms a thin, veil-like layer that closely follows the gyri and sulci on the surface of the brain. The pia and arachnoid matter are separated by a subarachnoid space that contains CSF and the major blood vessels supplying the brain. Vascular supply to the brain is divided into the anterior circulation arising from the internal carotid arteries and posterior circulation from the vertebral arteries (eFig. 9.20). The internal carotid arteries arise from the branching of the common carotid arteries at the level of the fourth cervical vertebra. Bilaterally the arteries course through the neck to enter the middle cranial fossa through the carotid canal. The arteries then make a series of turns to pass through the petrous portion of the temporal bone and cavernous sinus before entering the subarachnoid space just lateral to the optic chiasm. Upon exiting the cavernous sinus, the internal carotid artery gives rise to the ophthalmic artery and then continues superiorly to give off the posterior communicating artery and anterior choroidal arteries before terminating as the anterior and middle cerebral arteries (eFig. 9.21).

The two anterior cerebral arteries anastomose proximally via the anterior communicating artery, anterior to the optic chiasm (eFig. 9.22). Distal to this connection, the anterior cerebral artery (ACA) courses along the medial aspect of the cerebral hemisphere within the longitudinal fissure and follows the superior border of the corpus callosum to the anterior portion of the parietal lobe. Along its course two large branches arise: the callosomarginal artery, which follows the cingulate sulcus, and the pericallosal artery, which is immediately adjacent to the corpus callosum (eFig. 9.23). Given its course and branches, the ACA perfuses most of the medial aspect of the brain from the frontal lobe to the anterior portion of the parietal lobe. Branching laterally from the internal carotid artery, the middle cerebral artery (MCA) penetrates the lateral fissure and gives off the lenticulostriate striate arteries (eFig. 9.24) before bifurcating into superior and inferior divisions, which loop extensively along the insula and frontal operculum before emerging on the lateral convexity of the cerebrum. The superior division perfuses the cortex above the lateral fissure, including the lateral frontal lobe and a small portion of the anterior parietal lobe (eFig. 9.21). The inferior division perfuses the cortex below the lateral fissure, including the temporal lobe and the anterolateral portion of the parietal lobe. The posterior cerebral cortex receives vascular supply from the vertebral-basilar system of arteries. This system begins with the vertebral arteries bilaterally, which arise from the subclavian arteries and ascend through the foramen transversarium of the cervical vertebrae in the neck. After entering the foramen magnum at the level of the pontomedullary junction, the arteries join to form the basilar artery, which courses along the midline of the ventral brainstem (eFig. 9.20). At the level of the midbrain, the basilar artery gives rise to the posterior cerebral artery (PCA), which turns posteriorly and gives rise to branches that perfuse the inferior and medial temporal and occipital lobes. Also at the PCA, a connecting artery, the posterior communicating artery, branches off and connects to the internal carotid artery (eFig. 9.22). Venous drainage of the cerebral hemispheres follows a system of deep veins, superficial veins, and dural venous sinuses before reaching the internal jugular vein. Before reaching the internal jugular veins, the superficial and deep veins connect to the dural sinuses located between the periosteal and meningeal layers of the dura. None of the vessels in this network have valves present in their lumen.

Running along the superior edge of the falx cerebri is the superior sagittal sinus. The superior sagittal sinus continues posteriorly to drain into the transverse sinuses bilaterally (eFig. 9.25A). Each transverse sinus turns inferiorly to form the sigmoid sinus, which exits the jugular foramen to become the internal jugular vein. Along the inferior margin of the falx cerebri is the inferior sagittal sinus (eFig. 9.25B). Posteriorly, the inferior sagittal sinus joins the great vein of Galen to form the straight sinus. The point where the straight sinus, superior sagittal sinus, and occipital sinus join is known as the confluence of the sinuses (eFig. 9.25B). The confluence of sinuses is drained by the transverse sinuses. Located on either side of the hypophysial fossa is a plexus of veins referred to as the cavernous sinus (eFig. 9.26). In addition to receiving drainage from the other sinuses, the cavernous sinus also receives the ophthalmic veins. The cavernous sinus is drained by the superior petrosal sinus into the transverse sinus and inferior petrosal sinuses into the internal jugular vein. Venous drainage from the superficial veins is primarily received by the superior sagittal sinus and cavernous sinus. Although the pattern of superficial veins coursing through the subarachnoid space from the cerebral cortex is quite variable, three veins appear to be fairly constant. Positioned in parallel to the lateral fissure is the superficial middle cerebral vein, which drains into the cavernous sinus from the temporal lobe (eFig. 9.25A). Connecting to the superficial middle cerebral vein perpendicularly is the superior anastomotic vein (of Trolard) (eFig. 9.25A). This vein courses superiorly across the parietal lobe to drain into the superior sagittal sinus. Also connecting to the superficial middle cerebral vein perpendicularly is the inferior anastomotic vein (of Labbé) (eFig. 9.25A). The inferior anastomotic vein passes inferiorly along the temporal lobe to drain into the transverse sinus. In contrast to the superficial veins, deep veins are more constant in their organization. Most of the deep veins eventually drain into the great cerebral vein (of Galen) before entering the dural venous sinuses (eFig. 9.27). Traveling adjacent to the ACA and MCA are the anterior cerebral vein and deep middle cerebral vein. These deep veins join to form the basal vein (of Rosenthal), which continues around the lateral aspect of the midbrain. Formed at the interventricular foramen by the joining of the septal and thalamostriate veins bilaterally are the internal cerebral veins (eFig. 9.27). Posterior to the midbrain, the internal cerebral veins and basal veins join to form the great cerebral vein (of Galen) (eFig. 9.27). From here the great cerebral vein joins the inferior sagittal sinus to form the straight sinus. Part III: Thalamus The thalamus (Greek for “inner chamber”) is a large, egg-shaped mass of gray matter derived from the diencephalon of the developing brain (see eTable 9.1). The most significant role of the thalamus is as a synaptic relay for pathways projecting to the cerebral cortex. However, the thalamus also acts as a gatekeeper to prevent or enhance information transfer, depending on the behavioral state. Sensory, motor, limbic, and modulatory signals from behavioral and arousal circuits all have synaptic relays within the thalamic nuclei.

Because of its location deep within the brain, the thalamus is neighbored by several structures and also portions of the ventricular system. Anteriorly, the thalamus extends forward to contact the interventricular foramen, which connects the lateral and third ventricles (eFig. 9.28). Together, the thalamic nuclear masses and the ventrally located hypothalamus comprise the lateral walls of the third ventricle. Immediately lateral to the thalamus is the posterior limb of the internal capsule (eFig. 9.29). Related to the dorsal aspect of the thalamus is the body of the lateral ventricle, and extending caudally is the midbrain portion of the brainstem (eFig. 9.28). Across the midline of the third ventricle, the two thalamic masses are interconnected by the interthalamic adhesion. Based on their relationship to the internal medullary lamina, a Y-shaped band of myelinated axons coursing rostrocaudally through the thalamus, the thalamic nuclei are classified into four groups: (1) anterior, (2) medial, (3) lateral, and (4) intralaminar (eFig. 9.30). In addition to this structural categorization, the nuclei are divided into three major functional classes: (1) relay, (2) intralaminar, and (3) reticular. As mentioned earlier, most of the thalamus is composed of relay nuclei, which have reciprocal excitatory connections with the cortex. Relay nuclei are further subdivided into specific and nonspecific based on their projections to specific areas of the primary sensory and motor cortex or more diffuse cortical projections. The majority of specific relay nuclei reside in the lateral thalamus—in fact, all sensory modalities, with the exception of olfaction, have relays in the lateral thalamus before reaching their primary cortical target. Details of specific and nonspecific nuclei and their cortical connections can be reviewed in eTable 9.4. Intralaminar nuclei reside within the internal medullary lamina and have numerous reciprocal projections, primarily with the basal ganglia and reticular formation (eFig. 9.30).There are two major functional regions of the intralaminar nuclei: rostral and caudal. The rostral intralaminar nuclei have reciprocal connections with the basal ganglia and also relay input from the ascending reticular activating system. Caudal intralaminar nuclei, which include the large centromedian nucleus, are predominantly involved in basal ganglia circuitry. The reticular nucleus of the thalamus is a thin, sheet-like structure along the lateral aspect of the thalamus just medial to the posterior limb of the internal capsule (eFig. 9.30). Unlike the rest of the thalamic nuclei, the reticular nucleus does not send projections to the cerebral cortex, but rather receives input from other thalamic nuclei and the cortex, which project back to the thalamus. Functionally, this organization of inputs and outputs, along with the GABAergic neurons of the reticular nucleus, allows it to regulate thalamic activity quite effectively. Vascular supply to the thalamus arises from penetrating branches from the ACA, anterior choroidal artery branching from the internal carotid, lenticulostriate arteries of the middle cerebral artery and thalamoperforator arteries from the posterior cerebral arteries. Part IV: Brainstem

The brainstem is a stalklike structure within the posterior cranial fossa of the skull connecting the forebrain and spinal cord (eFig. 9.31). From rostral to caudal, the brainstem consists of the midbrain, pons, and medulla oblongata. Broadly speaking, the brainstem has three main functions: (1) it is a conduit for tracts ascending and descending through the CNS; (2) it houses cranial nerve nuclei III to XII (note that the CNXI is in the cervical spinal cord); and (3) it is the location for reflex centers related to respiration, cardiovascular function, and regulation of consciousness. Externally, each portion of the brainstem has a distinct appearance and structural features that define its many functional roles. Approximately 2 cm in length, the midbrain connects the forebrain to the pons caudally and the cerebellum posteriorly (eFig. 9.32A). Along the midline of the anterior surface there is a deep depression, the interpeduncular fossa, which has several perforations on its surface where small vessels perforate through the floor of the fossa. On either side of the interpeduncular fossa are the crus cerebri (eFig. 9.32B). Projecting medially from the crus is cranial nerve III, the oculomotor nerve (eFig. 9.33A). The most prominent features on the posterior surface are the superior and inferior colliculi (eFig. 9.32A). Between the inferior colliculi, cranial nerve IV, the trochlear nerve, emerges, crosses the midline, and wraps around the lateral aspect of the midbrain (eFig. 9.32A). Laterally, the superior brachium and inferior brachium can be seen as they project in an anterolateral direction from the superior and inferior colliculi. Caudal to the midbrain, the pons is approximately 2.5 cm in length and connects the midbrain to the medulla (eFig. 9.32B). The midline of the anterior surface has a shallow groove, the basilar groove, where the basilar artery resides along its course (eFig. 9.32B). On either side of the basilar groove, the pons has a prominent convex shape as a result of the vast number of fibers bridging through the pons to the cerebellum through the middle cerebellar peduncle. Along the anterolateral surface of the pons, cranial nerve V, the motor and sensory root of the trigeminal nerve, emerges (eFig. 9.33B). At the junction of the pons and medulla, from medial to lateral, cranial nerves VI (abducent), VII (facial), and VIII (vestibulocochlear) emerge (eFig. 9.33C). The posterior surface of the pons faces the cerebellum and forms the floor of the fourth ventricle (eFig. 9.32A). Along the midline of the posterior surface is a prominent bump, the facial colliculus, which represents the relationship between the facial nerve fibers as they wind around the nucleus of the abducent nerve (eFig. 9.33C).

The medulla is the longest portion of the brainstem, measuring approximately 3 cm in length (eFig. 9.32A). At the rostral connection of the medulla to the pons, it has a broad conical shape that tapers caudally before connecting with the spinal cord at the level of the foramen magnum. Along the midline of the anterior surface is the anterior median fissure, which continues on to the anterior surface of the spinal cord (eFig. 9.33B). Lateral to the fissure are the medullary pyramids composed of motor fibers descending from the cerebral cortex (eFig. 9.33B). Continuing caudally, the pyramids eventually give way to the decussation of the pyramids where the majority of motor fibers decussate to the opposing side. Lateral to the pyramids are the olives, which represent the underlying inferior olivary nuclei. It is at the junction of the pyramid and the olive that the rootlets of cranial nerve XII, the hypoglossal nerve, emerge (eFig. 9.33D). Oriented posterior to the olives are the inferior cerebellar peduncles, which form a connection between the cerebellum and medulla (eFig. 9.33D). At the junction of the olive and inferior cerebellar peduncles from rostral to caudal, rootlets of cranial nerves IX (glossopharyngeal), X (vagus), and XI (spinal accessory) emerge. Like the pons, the posterior surface of the medulla forms the floor of the fourth ventricle (eFig. 9.32A). Coursing down the midline of the posterior medulla is the posterior median sulcus, which continues into the spinal cord. On either side of the sulcus are the gracile and cuneate tubercles, formed by the underlying gracile nucleus and cuneate nuclei (eFig. 9.32A). Internal structures of the brainstem can be identified by their general location in the tectum (Latin for “roof”), tegmentum (Latin for “covering”), or basis (eFig. 9.34). To identify the structures present in each level of the brainstem, it is best to view serial sections stained for myelin. This way, nuclear groups and myelinated axons can be more easily distinguished from one another. The tectum is the most obvious landmark of the midbrain, as it consists of the prominent superior colliculi, inferior colliculi, and underlying cerebral aqueduct. Given the short length of the midbrain, stained serial sections typically include either the superior colliculi, which are located rostrally, or the inferior colliculi, which are caudal. In addition to the superior colliculi, within a rostral section of the midbrain prominent nuclei such as the oculomotor nuclei, Edinger–Westphal nuclei, red nuclei, mesencephalic nuclei of cranial nerve V, and substantia nigra can be seen (eFig. 9.35). In caudal sections of the midbrain the inferior colliculus, trochlear nucleus, mesencephalic nuclei of cranial nerve V, and substantia nigra are present (eFig. 9.36). Sections from the rostral pons are significant for pontine nuclei and multiple transversely oriented pontocerebellar fibers en route to the contralateral cerebellum. Interspersed among these horizontally running axon are longitudinally running corticospinal fibers (eFig. 9.37). Dorsal to this collection of fiber bundles, the medial lemniscus is oriented horizontally, forming a borderlike structure between the basal and tegmental portion of the pons (eFig. 9.37). At the lateral edge of the medial lemniscus, the spinothalamic tract can be seen, because it neighbors the superior cerebellar peduncle (eFig. 9.37). Near the midline, the medial longitudinal fasciculus resides just ventral to the periaqueductal gray matter.

At mid-pontine levels the superior cerbellar peduncles form the lateral walls of the expanding fourth ventricle (eFig. 9.38). Also at this level, the prominent middle cerebellar peduncles can also be seen, along with the motor nucleus and principal sensory nucleus of cranial nerve V, the trigeminal nerve. In the caudal aspect of the pons, the abducent nucleus can be appreciated just lateral to the medial longitudinal fasciculus (eFig. 9.39). Also present at this level is the medial vestibular nucleus in addition to the anterior and posterior cochlear nuclei. From rostral to caudal the internal structures of the medulla will be briefly described from three levels: (1) level of the inferior olivary nucleus, (2) decussation of the internal arcuate fibers, and (3) decussation of the pyramids. Nuclei visible in a transverse section at the level of the inferior olivary nucleus include those associated with cranial nerves VIII (vestibulocochlear), IX (glossopharyngeal), X (vagus), XI (spinal accessory), and XII (hypoglossal) (eFig. 9.40). At this level, the medial lemniscus maintains a vertical position immediately adjacent to the midline. Dorsal to the medial lemniscus are the medial longitudinal fasciculus and hypoglossal nucleus. A large distinguishing structure at this rostral level is the laterally oriented inferior cerebellar peduncle, which connects to the cerebellum posteriorly. Continuing caudally at the level of the internal arcuate fibers, the dorsal aspect of the medulla is populated by the gracile nucleus medially, followed by the cuneate and spinal trigeminal nucleus laterally. Ventral to the cuneate and gracile nuclei, their neuronal axons can be seen decussating as internal arcuate fibers to form the medial lemniscus near the midline of the medulla. Lateral to the internal arcuate fibers and ventral to the spinal trigeminal tract, the spinocerebellar and anterolateral tracts can be seen along the perimeter of the medulla (eFig. 9.41). Before transitioning into the spinal cord, the pyramidal decussation can be observed along the midline of the caudal medulla (eFig. 9.36). Dorsal to these decussating fibers, the gracile and cuneate nuclei begin to emerge as their fasciculi continue rostrally. Note that the spinal accessory nucleus (CN XI) is located in the cervical spinal cord and not the medulla. Vascular supply to the brainstem, and other structures in the posterior cranial fossa, is provided by branches off of the vertebrobasilar system of arteries. As mentioned in the “Cerebral Vasculature” section, the vertebrobasilar system begins with the vertebral arteries bilaterally, which arise from the subclavian arteries and ascend through the foramen transversaria of cervical vertebrae C6 to C2 in the neck. At the pontomedullary junction, the vertebral arteries fuse to form the single basilar artery. The basilar artery continues rostrally and terminates as the paired posterior cerebral arteries at the pontomesencephalic junction. Before merging and forming the basilar artery, each vertebral artery gives rise to a posterior inferior cerebellar artery (PICA) and posterior spinal artery and contributes to the formation of the anterior spinal artery (eFig. 9.42). The PICA perfuses the lateral aspect of the medulla and the inferior portion of the cerebellum. The medial and anterior portions of the medulla receive vascular supply from the paramedian branches off of the vertebral and anterior spinal arteries.

At the level of the caudal pons, the anterior inferior cerebellar artery (AICA) branches off of the basilar artery and perfuses the lateral portion of the caudal pons (eFig. 9.43A). Rostral levels of the lateral pons are perfused by circumferential branches of the basilar artery (eFig. 9.43A and B). Medial portions of the pons are perfused by paramedian branches off of the basilar artery as it continues rostrally toward the midbrain. Just before the midbrain, the superior cerebellar arteries branch off of the basilar artery and supply the superior cerebellar peduncles and caudal aspect of the dorsal midbrain before reaching the superior portion of the cerebellar hemispheres. Paramedian branches from the basilar artery supply the medial aspect of the midbrain (eFig. 9.43C). The final branches emerging from the top of the basilar artery are the PCAs, which perfuse the lateral aspect of the midbrain before reaching the thalamus, medial occipital, and inferior temporal lobes (eFig. 9.43C and D). Part V: Spinal cord The spinal cord is continuous with the medulla oblongata near the foramen magnum at the base of the skull. Cylindrical in shape, it occupies the vertebral canal of the vertebral column to the LI and LII vertebral level in an adult (eFig. 9.44). Numerous ascending and descending axonal tracts course through the spinal cord and connect with the brain to convey sensory (afferent) and motor (efferent) information for facilitation of movement, reflexes, sensory input, and feedback mechanisms. Like the brain, the spinal cord is surrounded by three concentric meninges: the dura mater, arachnoid mater, and pia mater. The spinal dura mater is continuous with the inner meningeal layer of the cranial dura mater and extends inferiorly to the posterior surface of the vertebral body of S2 (eFig. 9.45). It is separated from the bony vertebral canal by the epidural/extradural space (eFig. 9.45). In addition, unlike in the cranial cavity, the underlying arachnoid mater is not tightly adherent to the dura mater, and instead has a theoretical plane or potential space called the subdural space. Although the arachnoid mater of the spinal cord has a less adherent relationship with the dura mater than in the cranial cavity, the overall structure of the arachnoid mater is the same (eFig. 9.46A). The subarachnoid space created by the loose relationship of the arachnoid and underlying pia mater extends inferiorly to the level of the SII vertebra (eFig. 9.45). Given that the spinal cord terminates near the LI–LII vertebrae, this lower termination point of the subarachnoid space creates a safe and enlarged space for accessing CSF in the clinical setting (eFig. 9.45). The innermost pia mater is a highly vascular layer that is adherent to the surface of the spinal cord. Midway between the anterior and posterior roots the pia mater forms a flat continuous sheet, the denticulate ligament (eFig. 9.46B). At the posterior and anterior rootlets, sleevelike projections from the denticulate ligament extend out through the arachnoid mater to attach onto the dura mater. These delicate attachments anchor and position the spinal cord within the central area of the subarachnoid space.

The anterior and posterior surfaces of the spinal cord have several longitudinally running fissures and sulci. Along the midline on the anterior surface of the spinal cord is a deep separation, the anterior median fissure (eFig. 9.47). Posteriorly the spinal cord has a shallower separation, the posterior median sulcus, which is flanked on either side by a posterolateral sulcus (eFig. 9.47). Emerging from the spinal cord are a series of rootlets, which coalesce to form anterior and posterior roots at the corresponding cord segment (eFig. 9.48). These anterior and posterior roots converge to form 31 pairs of spinal nerves, which extend the length of the spinal cord (eFig. 9.44). Along the length of the spinal cord two regions are enlarged to accommodate the numerous neurons innervating the upper and lower extremities. The cervical enlargement extends from C5 to T1 and innervates the upper extremities, whereas the lumbar enlargement extends from L2 to S3 and innervates the lower extremities (eFig. 9.44). A cross-section of the spinal cord reveals an inner H-shaped gray matter consisting of neuronal cell bodies and an outer white matter composed of myelinated neuronal axons. The ventral or anterior horns of gray matter contain cell bodies of motor neurons, whereas the dorsal or posterior horns contain cell bodies receiving sensory information (eFig. 9.47). An enlargement of the lateral portion of the gray matter, termed the intermediolateral cell column, can be seen in the T1 to L2 region of the spinal cord (eFig. 9.49). This region enlarges to accommodate the preganglionic cell bodies of the sympathetic nervous system. To further define the diverse cytoarchitecture of the gray matter, it is divided into 10 zones known as Rexed’s laminae (eFig. 9.50). These will be referred to as they relate to later discussions of the ascending and descending tracts within the spinal cord. The anterior funiculus of the white matter consists of motor axons, whereas the posterior funiculus consists of axons conveying sensory information (eFig. 9.47). The lateral funiculus has a mixture of axons conveying both sensory and motor information. Sensory information entering the CNS from peripheral sensory receptors is conducted through a series of neurons that synapse with targets in the spinal cord, cerebral cortex, and other brain structures. The sensory modalities carried in these pathways include pain, temperature, tactile, and proprioceptive input. Conscious perception of sensory input is transmitted through neuronal pathways, which reach the primary somatosensory region of the cerebral cortex. In addition to conscious sensory input, there is subconscious sensory input, which is transmitted to other structures such as the cerebellum. For simplicity, in this section we will review the sensory pathways that reach conscious perception and discuss the pathways conveying subconscious sensory input in the section on cerebellum. Two somatosensory pathways ascend within the spinal cord to reach the cortex: (1) the anterolateral pathways, which convey sensations of pain, temperature, and crude touch; and (2) the posterior column–medial lemniscal pathway, which conveys sensations of discriminative or fine touch, vibration, and conscious proprioception (eFig. 9.51). Both of these pathways transmit information through a series of three neurons. We will review the anterolateral pathway first.

The anterolateral pathways are composed of three tracts: the spinothalamic, spinoreticular, and spinomesencephalic tract. Separate aspects of pain are conveyed through the spinothalamic tract, so we will follow the course of those neurons first. The first-order neuronal cell body of axons forming the spinothalamic tract is located in a spinal ganglion (eFig. 9.52). Axons then enter the spinal cord through the posterior root to reach the posterior horn. From here, axons have two courses: some synapse immediately on second-order neurons in the posterior horn gray matter (lamina I and V), and others have axonal collaterals that ascend or descend one to two spinal cord segments in the posterolateral tract of Lissauer before synapsing with the second-order neurons in the gray matter (eFig. 9.51). Axons of the second-order neurons then cross obliquely over two to three spinal cord segments within the anterior commissure of the spinal cord to join the anterolateral tract on the contralateral side (eFig. 9.52). These second-order axons ascend through the CNS to reach the third-order neuronal cell bodies in the ventral posterior lateral nucleus of the thalamus (eFig. 9.52). Axons from the third-order neurons then project through the posterior limb of the internal capsule to reach the primary somatosensory cortex (eFig. 9.52). The spinoreticular and spinomesencephalic tracts have a similar beginning as the spinothalamic tract. The principal difference is the target structure of the second-order axons. Rather than project to the thalamus as the spinothalamic tract does, the spinoreticular tract projects to the reticular formation in the brainstem to convey the emotional and arousal aspects of pain (eFig. 9.52), and the spinomesencephalic tract projects to the periaqueductal gray matter and superior colliculi in the midbrain for the central modulation of pain (eFig. 9.52). First-order neuronal cells bodies of the posterior column–medial lemniscal pathway are located in a spinal ganglion (eFig. 9.53). Axons then enter the spinal cord through the posterior root to reach either the gracile fasciculus (gracile means “thin”), which carries information from the lower limb and trunk, or the cuneate fasciculus (cuneate means “wedge-shaped”), which carries information from the upper limb and neck. These first-order axons then ascend ipsilaterally to the caudal medulla and synapse with the second-order neuronal cell bodies within the nucleus gracilis and nucleus cuneatus (eFig. 9.53). Axons of these second-order neurons then cross over as the internal arcuate fibers to form the medial lemniscus in the contralateral medulla (eFig. 9.53). These second-order axons ascend through the brainstem to reach the third-order neuronal cell bodies in the ventral posterior lateral nucleus of the thalamus (eFig. 9.53). Axons from the third-order neurons then project through the posterior limb of the internal capsule to reach the primary somatosensory cortex (eFig. 9.53). Descending tracts through the spinal cord are involved in voluntary movements; postural movements; and coordination of head, neck, and eye movements. These pathways originate from the cerebral cortex and brainstem and are influenced by sensory input and feedback circuitry from the cerebellum and basal ganglia. Structures that influence regulation of motor planning and voluntary control will be discussed in subsequent sections. In this section we will review the tracts of the medial and lateral motor systems. The tracts in each of these systems are composed of an upper motor neuron with cell bodies located in the cerebral cortex or brainstem and a lower motor neuron with cell bodies located in the spinal cord gray matter. We will begin by exploring the tracts of the lateral motor system first.

Tracts of the lateral motor system include the lateral corticospinal tract and rubrospinal tract. Both are located in the lateral column of the spinal cord white matter and synapse on lower motor neuronal cell bodies in the lateral aspect of the anterior horn gray matter. Clinically, the most important tract is the lateral corticospinal tract, because it is responsible for controlling movement of the upper and lower extremities. Cell bodies of upper motor neurons forming this tract are located in the primary motor cortex (eFig. 9.54). Axons of these upper motor neurons converge in the corona radiata and descend through the posterior limb of the internal capsule to reach the crus cerebri of the midbrain. These axons continue through the anterior aspect of the pons as small bundles to accommodate the transverse pontocerebellar fibers, which are also present in this location. Once the fibers reach the medulla, they are again grouped together and form a large swelling known as the pyramid (eFig. 9.54). At the caudal medulla, before transitioning into the spinal cord, most of the axons decussate over to the contralateral side to form the lateral corticospinal tract (eFig. 9.54). The remaining axons will stay ipsilateral and form the anterior corticospinal tract, a tract included in the medial motor systems. After decussating and forming the lateral corticospinal tract, the axons descend through the spinal cord to synapse on the cell bodies of lower motor neurons in the lateral portion of the anterior horn gray matter. Axons of these lower motor neurons then exit the spinal cord through the anterior root (eFig. 9.54). The other lateral motor system pathway is the rubrospinal tract (eFig. 9.55). Cell bodies of upper motor neurons in this pathway begin in the red nucleus of the midbrain. After leaving the red nucleus, the axons cross the midline as the ventral tegmental decussation and descend as the rubrospinal tract through the brainstem and lateral column of the spinal cord white matter (eFig. 9.55). These axons only descend to cervical regions of the spinal cord, and axons synapse with interneurons in the anterior horn gray matter to facilitate flexor muscle activity and inhibit extensor muscle activity of the upper limb. Tracts of the medial motor system regulate axial or truncal muscles involved in maintaining posture, balance, automatic gait-related movements, and orientating movements of the head and neck. Unlike the lateral motor system, the tracts in this system primarily project bilaterally on interneurons within the spinal cord. This makes it difficult to test each tract individually in the clinical system. We will briefly review the four tracts of the medial motor system beginning with the anterior corticospinal tract. The anterior corticospinal tract is formed by the remaining descending upper motor neurons that did not decussate in the caudal medulla to form the lateral corticospinal tract. These upper motor neurons, which remain ipsilateral to form the anterior corticospinal tract, descend through the medial aspect of the anterior spinal cord to the level of the upper thoracic region (eFig. 9.54). These axons project bilaterally to synapse on cell bodies of lower motor neurons in the medial portion of the anterior horn gray matter. Axons of these lower motor neurons then exit the spinal cord through the anterior root. Tectospinal tract axons arise from cell bodies located in the superior colliculus of the dorsal midbrain (eFig. 9.56). These axons decussate in the dorsal tegmental decussation shortly after leaving the nucleus to form the tectospinal tract along the midline of the brainstem. The tectospinal tract continues through the brainstem near the medial longitudinal fasciculus and into cervical regions of the spinal cord near the anterior median fissure. Within the cervical spinal cord, axons project bilaterally to synapse on cell bodies of interneurons in the anterior horn gray matter. As the superior colliculus receives visual input, it is believed that the tectospinal tract modulates reflex postural movements in response to visual stimuli.

Vestibulospinal tract axons arise from vestibular nuclei located in the pons and medulla. The medial vestibular nucleus gives rise to the medial vestibulospinal tract, which projects bilaterally to thoracic regions of the spinal cord, and the lateral vestibular nucleus gives rise to the lateral vestibulospinal tract, which descends ipsilaterally through the entire length of the spinal cord to synapse on interneurons in the anterior horn gray matter (eFig. 9.57). Given that the vestibular nuclei receive sensory input from the inner ear and cerebellum, this tract facilitates activity of extensor/antigravity muscles and inhibits activity of flexor muscles to maintain balance and an upright posture. As an example, the change in head position induced during tripping initiates extension of the upper limb and/or lower limb to prevent oneself from falling forward. Reticulospinal tract axons arise from the reticular formation in the pons and medulla. The axons of the pontine and medullary reticulospinal tracts descend ipsilaterally through the length of the spinal cord in the anterior white matter and synapse with interneurons in the anterior horn gray matter. They are believed to function in regulating voluntary movements in reflex activity and autonomic outflow (eTables 9.5 and 9.6). Vascular perfusions to the spinal cord are supplied by three longitudinally running vessels and several segmental branches. The longitudinally running vessels are the anterior spinal artery and two posterior spinal arteries. The posterior spinal arteries originate in the cranial cavity as branches of either the vertebral artery or PICA. These arteries descend along the length of the posterior spinal cord on the posterolateral sulcus. The single anterior spinal artery originates within the cranial cavity from the union of two contributing branches from the vertebral arteries. The anterior spinal artery descends along the length of the anterior spinal cord on the anterior median fissure. Reinforcing vascular supply to these longitudinally running vessels is provided by eight to ten segmental medullary arteries. The largest segmental medullary artery is the artery of Adamkiewicz in the lower thoracic or upper lumbar region. This vessel is typically on the left side and contributes significantly to perfusion of the lower portion of the spinal cord. Venous drainage of the spinal cord occurs through a series of longitudinally running channels that connect with the anterior and posterior spinal veins on the surface of the cord. Part VI: Basal nuclei The basal nuclei are a collection of gray-matter structures named for their location deep within the base of the forebrain. Functionally, the basal nuclei have a significant role in controlling posture and voluntary movement through connections to the thalamus, cortex, and neighboring basal nuclei structures. In addition to their role in posture and movement, the basal nuclei have connections to limbic system pathways, which govern the expression of various behaviors and motivational states. For the purposes of this section, we will focus on reviewing the structures of the basal nuclei and pathways involved in controlling posture and voluntary movement. A variety of terminology is used to refer to the structures of the basal nuclei individually and based on their collective morphology. To appreciate the three-dimensional shape of the basal nuclei and their relationship to surrounding structures, it is best to view them in horizontal and coronal brain sections taken at different levels of the brain. The corpus striatum (Latin for “striped body”) includes the caudate nucleus and lentiform nucleus. This collection of structures received their name because of the striated appearance of bands that interconnect the caudate nucleus and putamen of the lentiform nucleus through the anterior limb of the internal capsule (eFig. 9.58).

The lentiform nucleus (Latin for “lens-shaped”) includes the globus pallidus and putamen, which appear lens-shaped when viewed laterally. Both of these structures are lateral to the internal capsule, which separates them from the thalamus and caudate nucleus medially (eFig. 9.58). Laterally, the putamen is bordered by the external capsule, a thin layer of white matter adjacent to a thin gray-matter layer called the claustrum. Beyond the claustrum is the external capsule, which borders the white matter of the insula (eFig. 9.58). Medial to the internal capsule is the caudate nucleus. The caudate nucleus is a large C-shaped structure divided into a head, body, and tail, which closely follows the shape of the lateral ventricle (eFig. 9.58). Rostrally, the head of the caudate has a large rounded shape that contributes to the lateral wall of the anterior horn of the lateral ventricle (eFig. 9.58). Also at this level, the head of the caudate is continuous with the putamen (eFig. 9.59). Because of this close relationship the putamen and caudate are referred to collectively as the striatum. At the level of the interventricular foramen, the head of the caudate transitions to the body. The body of the caudate is long and narrows substantially as it transitions from the head to the tail (eFig. 9.59). Along its course the body contributes to the floor of the lateral ventricle. Near the posterior border of the thalamus the body of the caudate transitions into the tail. The tail continues anteriorly within the roof of the inferior horn of the lateral ventricle to terminate in the amygdaloid nucleus (eFig. 9.59). Input to the basal nuclei is primarily received by the striatum (caudate nucleus and putamen), and output predominantly leaves from the globus pallidus. Many structures send input to the striatum, including all areas of the cerebral cortex, thalamic nuclei, subthalamic nucleus, brainstem, and substantia nigra. To understand how the basal nuclei integrates all of this incoming information to influence motor activity, two simplified neuronal loops are described: the direct pathway and the indirect pathway. The direct pathway has a series of connections through the basal nuclei, which result in an overall increase in motor activity. This pathway begins with input to the striatum, which sends axonal connections to the globus pallidus (eFig. 9.60A). The globus pallidus then has output connections to the thalamus, which completes the circuit with axonal connections back to the cortex. The indirect pathway has a similar course, with the addition of output connections to the subthalamic nucleus, which results in an overall decrease in motor activity (eFig. 9.60B). Part VII: Cerebellum The cerebellum is the largest structure of the hindbrain. It resides within the posterior cranial fossa and is composed of two large hemispheres, which are connected by the vermis in the midline (eFig. 9.61). Functionally, the cerebellum plays a role in maintaining balance and influencing posture and is responsible for coordinating movements by synchronizing contraction and relaxation of voluntary muscles. We will first examine the structural organization of the cerebellum and then review how these structures contribute to the circuitry of the cerebellum.

Within the posterior cranial fossa, the cerebellum is covered by the tentorium cerebelli of the dura mater (eFig. 9.17) and connects to the posterior surface of the brainstem via the superior, middle, and inferior cerebellar peduncles (eFig. 9.62). Anteriorly, the cerebellum forms the roof of the fourth ventricle (eFig. 9.14). On its surface, the cerebellum has several convoluted folds, or folia, separated by fissures. Two of these fissures serve as landmarks to divide the cerebellum into three lobes. Superiorly, the primary fissure separates the anterior lobe from the posterior lobe (eFig. 9.61). Anteriorly and inferiorly, the posterolateral fissure defines the structures of the flocculonodular lobe, which includes the flocculus from each hemisphere and nodule of the vermis (eFig. 9.63). A third fissure, the horizontal fissure, borders the superior and inferior surfaces of the cerebellum (eFig. 9.64). Each fold or folia of the cerebellar cortex has a central core of white matter covered by a thin layer of gray matter superficially. In sections parallel to the median plane, the branching pattern of the folia can be appreciated; this is often referred to as the arbor vitae (eFig. 9.28). Deep within the white matter of each hemisphere are four masses of cerebellar nuclei. From lateral to medial they are the dentate, emboliform, globose, and fastigial (eFig. 9.65). Note that the emboliform and globose are collectively referred to as the interposed nuclei. Output from the cerebellum originates from one of these four nuclear complexes before leaving through the superior cerebellar peduncle, predominantly. In general, the output from each cerebellar hemisphere coordinates movement on the ipsilateral side of the body. Functionally, the cerebellar cortex can be divided into three areas. The vermis in the midline influences movements along the axis of the body, including the neck, trunk, abdomen, and pelvis (eFig. 9.66). Adjacent to the vermis, the intermediate zone controls muscles of the distal upper and lower limbs. The lateral zone participates in motor planning to coordinate sequential movements of the entire body. Input to these functional areas of cerebellar cortex come from the cerebral cortex, spinal cord, and brainstem by passing predominantly through the middle and inferior cerebellar peduncles. Fibers entering the cerebellum proceed as mossy fibers (from various regions) or climbing fibers (from olivary nucleus). Mossy fibers form excitatory synapses with dendrites of the granule cells, in the granule cell layer (eFig. 9.67). From here, the granule cells send axons to the molecular layer, where they bifurcate into parallel fibers that run longitudinally in the folia. The parallel fibers then synapse on Purkinje cells in the outermost Purkinje cell layer (eFig. 9.67). Climbing fibers project to the Purkinje cell layer and form powerful excitatory connections with the Purkinje cells. The Purkinje cells then project to the deep cerebellar nuclei (eFig. 9.67). As mentioned earlier, the cerebellum receives input from the cerebral cortex, brainstem, and spinal cord. Input from the cerebral cortex to the cerebellum is primarily involved in voluntary muscle control and coordination of movement. Axonal projections from the cerebral cortex destined for the cerebellum descend through the internal capsule and terminate on pontine nuclei (eFig. 9.68). The axons from the pontine nuclei then cross over as transverse fibers to enter the contralateral cerebellum through the middle cerebellar peduncle.

Input from the spinal cord to the cerebellum conveys information from muscles and joints to influence muscle tone and posture. The primary spinal cord pathways with connections to the cerebellum include the anterior or ventral spinocerebellar and the posterior or dorsal spinocerebellar tracts. These tracts originate from joint and cutaneous mechanoreceptors and ascend through the spinal cord to enter the ipsilateral cerebellum primarily through the inferior cerebellar peduncle (eFig. 9.69). A final source of cerebellar input arises from the vestibular nuclei and reticular formation in the brainstem. The connections are primarily involved in reflexive maintenance of balance. These nuclei send axonal projections to the ipsilateral cerebellum through the inferior cerebellar peduncle. Output from the cerebellum originates from one of the four deep cerebellar nuclei. The largest collection of fibers leaving the cerebellum originates from the dentate nucleus. Axons from this nuclear complex project to the contralateral ventral nucleus of the thalamus after decussating in the superior cerebellar peduncle. From here, axons of the thalamic nuclei project to the motor cortex (eFig. 9.70). This pathway influences posture and movement. The emboliform and globose nuclei, or interposed nuclei, have a similar course as the axons from the dentate, but with the addition of another synaptic target. Axons from the interposed nuclei decussate in the superior cerebellar peduncle to synapse on the contralateral ventral nucleus of the thalamus and the contralateral red nucleus in the midbrain (eFig. 9.70). Axons leaving the red nucleus descend to the inferior olivary nucleus in the medulla. The axonal projections from the interposed nuclei function in monitoring and correcting motor activity of the upper and lower extremities. Axons from the fastigial nucleus project to the vestibular nuclei, reticular formation, contralateral ventral nucleus of the thalamus, and contralateral tectum. Vestibular axons pass through the inferior cerebellar peduncle to reach the ipsilateral vestibular nucleus and uncinate fasciculus to reach the contralateral vestibular nucleus (eFig. 9.70). Also going through the inferior cerebellar peduncle are axons heading to the reticular formation. Ascending in the superior cerebellar peduncles are axons that will synapse with the contralateral tectum and contralateral ventral nucleus of the thalamus. The cerebellum is perfused by the vertebrobasilar system of arteries (eFig. 9.42). Before merging and forming the basilar artery, each vertebral artery gives rise to a PICA and posterior spinal artery and contributes to the formation of the anterior spinal artery (eFig. 9.71). The PICA perfuses the inferior portion of the cerebellum. At the level of the caudal pons, the AICA branches off the basilar artery and perfuses the anterior and lateral portion of the cerebellum, as well as the middle and inferior cerebellar peduncles (eFig. 9.71). Just before the midbrain, the superior cerebellar arteries branch off of the basilar artery and supply the superior cerebellar peduncles and superior portion of the cerebellar hemispheres (eFig. 9.71). Part VIII: Visual System The visual system is a complex special sensory system that begins in the eyeball and has neuronal connections to the thalamus, brainstem, primary visual cortex, and association cortices. In addition to mediating visual perception, these connections are also involved in higher visual functions, such as determining spatial relationships between objects and structural features of objects. In this section we will explore the primary or geniculate visual pathway from the retina to the primary visual cortex.

Although the retinal layer of the eyeball is often considered the beginning of visual perception, the anterior structures of the eye play an important role in visual perception too. The anteriormost structure is the cornea and is the first layer through which light, the visual stimulus, enters the eye (eFig. 9.72). This transparent layer overlies the aqueous humor of the anterior chamber and the pupil, a small central aperture that controls how much light is admitted into the eye. After passing through the pupil light is refracted through the lens, which along with the ciliary body, separates the anterior portion of the eye from the posterior portion (eFig. 9.72). The lens is a clear biconvex structure that rounds in shape as the ciliary muscle contracts and relaxes the suspensory ligaments attached to the borders of the lens, a parasympathetically controlled process referred to as accommodation. After the lens, light passes through the vitreous humor of the posterior chamber and is projected onto the layers of the retina (eFig. 9.73). The retina is composed of a non-neural layer and several layers of neural cells with synaptic connections. To reduce the amount of light reflected in the eye, the choroid layer lining the inner surface of the sclera (eFig. 9.72), along with the pigment epithelium layer (non-neural) of the retina, absorb and refract some of the light stimulus (eFig. 9.73). Interdigitating between the pigment epithelial cells, the photoreceptors transduce the light stimulus into an electrical signal in a process called phototransduction. Images formed on the retina are inverted in both vertical and lateral dimensions (eFig. 9.74). Because of this, the visual field is defined as having four quadrants: left/right and upper/lower. Photoreceptors include rods, which are very sensitive to light and essential for vision in dimly lit conditions, and cones, which are responsible for color vision and high visual acuity. Although rods and cones are both distributed across the retina, rods outnumber cones by twentyfold and are concentrated in the periphery of the retina. Cones predominate near the macula and are the only photoreceptors present at the fovea (eFig. 9.72). The fovea represents the primary visual axis of the eye and is the location of maximal visual acuity. Despite their functional differences, both the rods and cones have an outer light-sensing segment, an inner segment, and a synaptic terminal. These synaptic terminals contact bipolar cells, the first-order neurons in the visual pathway (eFig. 9.73). Bipolar cells then synapse with ganglion cells, the second-order neurons in the visual pathway. Two other cell types present in the retina are horizontal and amacrine cells. These transversely oriented interneurons moderate the excitation level of bipolar and ganglion cells. Axons from the ganglion cells coalesce at the optic disc, which is absent of photoreceptors and thus creates a blind spot in the visual field. As they leave the optic disc they form the optic nerve, acquire a myelin sheath provided by oligodendrocytes, and are invested by the cranial meninges (eFig. 9.72). These morphological features derived during embryonic development, define the optic nerve as a component of the CNS. Anterior to the infundibular stalk, the optic nerves converge at the optic chiasm. Within the chiasm, axons from the nasal portion of the retina decussate and enter into the contralateral optic tract (eFig. 9.75). Conversely, axons from the temporal portion of the retina stay ipsilateral to enter the ipsilateral optic tract (eFig. 9.75).

Continuing posteriorly, the optic tracts course around the midbrain to enter the lateral geniculate nucleus of the thalamus (eFig. 9.75). At this level, a small portion of the fibers from the optic tract travel to the pretectal area and superior colliculus to mediate the pupillary light reflex. Axons leaving the lateral geniculate nucleus form the optic radiations, which continue on to the primary visual cortex in the occipital lobe (eFig. 9.76). Fibers traveling in the lower portion of the optic radiations terminate on the lower half of the primary visual cortex, whereas fibers in the upper portion terminate on the upper half of the cortex (eFig. 9.76). A full review of how the visual field is represented throughout the visual pathway can be reviewed in eFig. 9.77. As mentioned previously, images formed on the retina are inverted in both vertical and lateral dimensions. In addition, the fibers from the nasal portion of the hemiretina decussate at the optic chiasm. Because of this, the optic tracts, thalamus, optic radiations, and primary visual cortex receive information relating only to the contralateral half of the visual field. Knowledge of how the visual field is represented throughout the visual pathway is essential for identifying the location of lesions in patients with visual field deficits. Examples of lesions in the five major structures of the visual pathway (optic nerve, optic chiasm, optic tract, optic radiations, primary visual cortex) and their associated visual field deficits are represented in eFig. 9.78. Part IX: Auditory and Cranial nerve VIII, the vestibulocochlear nerve, conveys sensory information from the vestibular and auditory organs of the inner ear to the pontomedullary junction of the brainstem. Although these sensory modalities are conveyed to the brainstem by a common nerve bundle, each of these sensory functions has different central pathways. In this section we will first review the central auditory pathways and then the vestibular pathways. Sound waves, the auditory stimulus, are directed toward the external acoustic meatus by the pinna of the outer ear and through the ear canal to the tympanic membrane (eFig. 9.79). Vibration of the tympanic membrane, induced by the incoming sound waves, is transmitted to the three ossicle bones (malleus, incus, and stapes) of the middle ear. These bones amplify sound waves so they can be converted to pressure waves at the oval window of the fluid-filled cochlea. To prevent damage from loud or high-decibel sounds, movements of the malleus and stapes are reduced by the tensor tympani and stapedius muscles. In the cochlea, sound waves are converted into an electrical signal at the organ of Corti. The organ of Corti rests upon the basilar membrane in the scala media, which is filled with endolymph (eFig. 9.80). In addition to contributing to the formation of the scala media with the vestibular membrane, the basilar membrane separates the cochlea into the scala vestibuli and scala tympani, which are filled with perilymph and are continuous with one another at the helicotrema (eFig. 9.80). As the sound waves move through the perilymph they displace the basilar membrane, which causes deflection of the hair cells in the organ of Corti (eFig. 9.81A). These sensory receptors synapse with sensory neurons, which have cell bodies in spiral ganglion located within the modiolus of the cochlea (eFig. 9.80). Axons leaving the modiolus form the cochlear nerve near the base of the cochlea. The cochlear nerve then passes through the internal acoustic meatus and subarachnoid space to enter the pontomedullary junction at the cerebellopontine angle.

The first-order axons entering the brainstem from the cochlea terminate ipsilaterally on the dorsal and ventral cochlear nuclei. From here, second-order axons have several synaptic targets. Second-order axons forming the ascending auditory pathway ascend to the pons and project bilaterally on the superior olivary nucleus (eFig. 9.82). These bilateral projections are important for auditory acuity and localizing the origin of a sound. From here, fibers continue to ascend as the lateral lemniscus and terminate in the inferior colliculus of the midbrain. Axons leaving the inferior colliculus then have a synaptic relay in the medial geniculate nucleus of the thalamus before reaching the final synaptic target: the primary auditory cortex (superior temporal gyrus) of the temporal lobe (eFig. 9.82). Throughout this pathway, from the basilar membrane to the primary auditory cortex, auditory stimuli are tonotopically represented. This is analogous to the somatotopic map previously discussed in the section on somatosensory systems pathways. In addition to the ascending auditory pathway, the superior olivary nucleus receives descending input from the primary auditory cortex as a form of feedback (eFig. 9.82). The superior olivary nucleus then sends descending olivocochlear fibers to the organ of Corti, which has an inhibitory function on the hair cells to prevent damage from harmfully loud sounds. It is also believed that the superior olivary nucleus has connections with the motor nuclei of the trigeminal and facial nerve to mediate reflexive contraction of the tensor tympani and stapedius muscles in response to loud sounds. The vestibular nerve transmits afferent or sensory information regarding movement and position of the head from the vestibular organs, which include semicircular ducts, utricle, and saccule. Like the cochlear apparatus, each of these vestibular organs is located within a membranous (ductal) portion of the vestibular apparatus, which is surrounded by a bony (canal) portion (eFig. 9.83). The cell bodies for these sensory receptors are located in the vestibular (Scarpa’s) ganglion within the internal acoustic meatus (eFig. 9.83). The vestibular nerve then passes through the internal acoustic meatus and subarachnoid space to enter the pontomedullary junction at the cerebellopontine angle. The central processes of the vestibular axons predominantly terminate in the four vestibular nuclei (superior, inferior, medial, and lateral), which are located in the rostral medulla and caudal pons (eFig. 9.40). Axons leaving the vestibular nuclei have several ascending and descending synaptic targets. These pathways connect with visual motor, descending motor, and cerebellar pathways to coordinate movement and maintain posture and balance (eFig. 9.84). Axons ascending after leaving the vestibular nuclei form the medial longitudinal fasciculus to reach the oculomotor, trochlear, and abducent nuclei (eFig. 9.85). These connections coordinate movement of the head and eyes so that visual fixation on an object can be maintained. Other axons ascending from the vestibular nuclei project to the cerebral cortex after a synaptic relay in the ventral posterior nucleus of the thalamus (eFig. 9.84B). This connection assists in consciously orienting oneself in space. In addition to these connections, axons leaving the vestibular nuclei pass through the inferior cerebellar peduncle to reach the cerebellum and modulate equilibrium (eFig. 9.84B). Axons descending after leaving the vestibular nuclei form the medial and lateral vestibulospinal tracts ipsilaterally (eFig. 9.84B). As mentioned in the previous section on medial motor systems in the spinal cord, the axons in these pathways synapse on interneurons within the anterior horn gray matter to influence spinal motor neuron activity and maintain posture and balance. Part X: Hypothalamus

The hypothalamus is a neuroendocrine organ that regulates physiological processes for survival such as consumption of fluid and food, temperature control, the sleep–wake cycle, growth, and reproduction. As a result of this vast array of functions, the nuclei of the hypothalamus make connections with several other neural and endocrine structures in the body (eFig. 9.86). In this section we will explore the nuclei of the hypothalamus and their main connections. Located in the ventralmost aspect of the diencephalon, the hypothalamus is bounded by the lamina terminalis anteriorly, the hypothalamic sulcus superiorly, and the tegmentum of the midbrain posteriorly (eFig. 9.87). Laterally the hypothalamus is bordered by the substantia innominata rostrally and the posterior limb of the internal capsule caudally. It forms the floor in addition to the lower portion of the lateral walls in the third ventricle. When viewing the external surface of the ventral brain, the area containing the hypothalamus is circumscribed by the optic chiasm, optic tract, crus cerebri, and caudal edge of the mammillary bodies (eFig. 9.88). Continuous with the hypothalamus inferiorly is the pituitary gland. These two structures are connected by the infundibulum and hypophysial stalk just caudal to the optic chiasm (eFig. 9.87). The intimate relationship of the hypothalamus to the portal circulation of the pituitary gland allows the hypothalamus to be an efficient regulator of hormone synthesis and release. Releasing and inhibiting factors synthesized by the hypothalamus pass through these portal vessels via the tuberoinfundibular tract (eFig. 9.89) to reach the anterior pituitary (adenohypophysis) and control release of hormones produced by the anterior pituitary such as adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, growth hormone, and prolactin (eFig. 9.90). A second connection exists between the hypothalamus and pituitary through nerve fibers, which originate in the supraoptic region and paraventricular nuclei of the medial hypothalamus and extend through the hypothalamohypophyseal tract to the posterior lobe of the pituitary for release into the circulatory system (eFig. 9.89). Internally, the hypothalamus is composed of many small nuclei, which are divided by a parasagittal plane into a medial and lateral zone. Landmarks for this dividing point are the columns of the fornix and the mammillothalamic tract as they reside within this sagittal plane (eFig. 9.91). The hypothalamus is also divided by coronal planes into a preoptic area and periventricular zone. Note that the periventricular zone is not to be confused with the paraventricular nucleus, which is a thin region of cell bodies lying medial to the medial zone. Within the lateral zone of the hypothalamus is a large bundle of axons forming the medial forebrain bundle (MFB) (eFig. 9.90). Theses fibers interconnect the hypothalamus with the septal nuclei rostrally and nuclear complexes within the brainstem. Axons arising from the large lateral nucleus in this zone enter the MFB and function in promoting feeding behavior. The other and smaller nuclear group in this zone is the tuberal group. Axons from the tuberal nuclei make connections with the anterior pituitary through the tuberoinfundibular tract to regulate release of hormones in the hypophysial portal system and to the cerebellum to regulate motor activity (eFig. 9.89).

The medial zone is divided into three regions: supraoptic, tuberal, and mammillary. There are four nuclei in the supraoptic region, which play a role in thermoregulation, osmoregulation, and the sleep–wake cycle. The supraoptic and paraventricular nuclei in this region synthesize antidiuretic hormone or vasopressin, which stimulates water uptake and oxytocin for stimulation of uterine contractions and lactation in the mammary glands. Axons from these nuclei are conveyed by the hypothalamohypophyseal tract to the posterior pituitary for release into the circulatory system (eFig. 9.89). A third nuclear group in this region is the suprachiasmatic nucleus. This nucleus receives input directly from the retina to influence circadian rhythms, which contribute to the light–dark cycle. The anterior nucleus is the final group and functions predominantly in regulating body temperature. The tuberal region in the medial zone contains three nuclei: ventromedial, dorsomedial, and arcuate. The largest and best defined is the ventromedial nucleus, which functions as a satiety center to decrease feeding behavior. Posterior to the ventromedial nucleus is the dorsomedial nucleus, which functions in the behavioral expression of rage or aggressive behavior. Finally, the arcuate nucleus serves as a center for releasing hormones, which are transmitted by the tuberoinfundibular tract and hypophysial portal system to the anterior pituitary (eFig. 9.89). The mammillary region or mammillary body is the final group of nuclei in the medial zone. Four nuclei comprise this region: medial, intermediate, lateral mammillary, and posterior hypothalamic. The best defined is the medial mammillary nucleus, as it is the primary site for the termination of axons from the postcommissural fornix. This pathway originates from the subiculum of the hippocampal complex and plays a key role in memory. The medial mammillary nuclei also connects to structures of the limbic system. The periventricular zone resides medial to the medial zone and adjacent to the ependymal cells of the third ventricle. Neurons from this zone predominantly synthesize releasing hormones. Axons from these neuronal cells project through the tuberoinfundibular tract to the hypophysial portal system to influence release of hormones from the anterior pituitary. Through the review of the hypothalamus thus far, it is apparent that this small, 4-gram structure has a significant role in regulating visceral, endocrine, and behavioral system functions through multiple pathways. It is important to remember the majority of the pathways mentioned represent input–output relationships between the hypothalamus and other structures. For a review of neural and non-neural inputs and outputs, refer to the summary figures (eFig. 9.92A and B). Part XI: Olfactory and The sense of olfaction has a role in both pleasurable experiences and survival. The same receptors that allow us to enjoy the food we consume or experience odorants in the environment also help us avoid spoiled food or potentially hazardous situations like a fire. Unlike the other special sensory system pathways, the olfactory sensory pathway is unique in that it does not have a thalamic relay before reaching the primary olfactory cortex. In this section we will review the course of the neurons in the olfactory system and their connection to the limbic system. Three types of olfactory receptors make up the olfactory epithelium along the lateral and septal walls of the nasal cavity. These cells allow for regeneration (basal stem cells), support (sustentacular cells), and transmission of information (olfactory receptor neurons). Each olfactory receptor neuron has an olfactory vesicle with cilia that contain receptors for odorant molecules and an unmyelinated axon that passes through the cribriform plate to terminate in the olfactory bulb (eFig. 9.93). As the olfactory receptor neurons originate embryologically from the CNS, they are considered part of the CNS and not the PNS.

After synapsing with the mitral cells in the glomeruli of the olfactory bulb, mitral cell axons converge to form the olfactory tract. The olfactory tract then divides into medial and lateral olfactory striae to reach different synaptic targets (eFig. 9.94). Some of the axons in the medial olfactory striae travel through the diagonal band to reach the septal area, whereas others cross the midline in the anterior commissure and inhibit mitral cell activity in the contralateral olfactory bulb to enhance localization of the olfactory stimulant. Axons in the lateral olfactory stria primarily terminate in the piriform cortex/primary olfactory cortex of the uncus and in the amygdala (eFig. 9.94). The medial forebrain bundle, traveling through the lateral hypothalamus, connects the olfactory cortex with both the hypothalamus and the brainstem to regulate autonomic responses such as arousal through the reticular formation, salivation, and gastric contraction. The limbic system is composed of several cortical and subcortical structures that participate in an intricate network of connections to regulate complicated behaviors such as memory, emotions, homeostatic functions, and motivational state. In this section we will review the major structures and pathways that form the limbic system. Grossly, the limbic lobe includes a ring-shaped area of cortical structures that border the brainstem. These cortical areas include the cingulate gyrus, parahippocampal gyrus, and subcallosal area (eFig. 9.12). Laterally, the insular cortex also participates in limbic system function (eFig. 9.10). Nuclear structures of the limbic system include the amygdala, hippocampal formation, anterior and mediodorsal thalamic nuclei, septal nuclei in the forebrain, and nucleus accumbens (eFig. 9.95). The amygdaloid nucleus is an almond-shaped structure located anterior to the inferior horn of the lateral ventricle and tail of the caudate within the temporal lobe (eFig. 9.96). Structurally, the amygdala consists of three nuclear regions: a large basolateral group and a smaller corticomedial group, which includes the central nucleus. Functionally, the amygdala is primarily associated with the emotion of fear, but it also has an important role in autonomic and neuroendocrine pathways. Connections of the amygdala are predominantly bidirectional and follow three different pathways: the uncinate fasciculus, stria terminalis, and ventral amygdalofugal pathway (eFig. 9.97). Connections to cortical areas pass through the uncinate fasciculus, which progresses anterior to the amygdala. Projections to the septal area and hypothalamus follow the stria terminalis (eFig. 9.98A–D). Fibers forming the ventral amygdalofugal pathway project to thalamic nuclei and several brainstem and forebrain structures (eFig. 9.98A–D). The nucleus accumbens resides with the ventral forebrain adjacent to where the putamen and head of the caudate become continuous with one another (eFig. 9.99). Afferent axons to the nucleus accumbens come from the amygdala through the amygdalofugal pathway, hippocampal formation by way of the fornix, basal forebrain area from the stria terminalis, and ventral tegmentum through the medial forebrain bundle (eFig. 9.98A–D). Efferent axons leaving the nucleus accumbens project directly to the hypothalamus and globus pallidus and reach nuclei in the brainstem through the medial forebrain bundle. Its connections to the globus pallidus represent an important connection of the limbic system to the motor system. The overall function of the nucleus accumbens is recognized as a gratification center and has been shown to play a role in behaviors related to addiction.

The septal region is located rostral to the anterior commissure along the medial aspect of the cerebral hemispheres (eFig. 9.99). This region appears to play a role in pleasurable behaviors. Conversely, lesion studies indicate that damage to this area evokes behaviors of extreme displeasure or rage. Afferent axons to the septal area arise from the amygdala, hippocampus, olfactory tract, and monoaminergic nuclei in the brainstem (eFigs. 9.100 and 9.101). The septal area also connects to a collection of cholinergic neurons along the wall and roof of the third ventricle known as the habenular nuclei. Axons from the habenular nuclei project to the interpeduncular nucleus of the reticular formation, which is believed to play a role in the sleep–wake cycle (eFig. 9.100). The hippocampal formation is located in the medial ventral temporal lobe (eFig. 9.102). It consists of the hippocampus, dentate gyrus, and subiculum (eFig. 9.103A and B). The hippocampal formation plays a role in memory processes such as episodic memory, short-term memory, working memory, and consolidation of memories. Input to the hippocampal formation is primarily received by the entorhinal cortex from association cortices. Because of this, it is believed that the “storage” of memories is in the association and primary cortices, not in the medial temporal lobe. Neurons from the entorhinal cortex project to the hippocampal formation by two pathways: the perforant pathway and alvear pathway. The perforant courses directly through the hippocampal sulcus to reach the dentate gyrus (eFig. 9.104B). As the hippocampus resembles the appearance of a ram’s horn, early on it was named cornu ammonis (horn of Ammon). Based on its cytoarchitecture, it was subdivided into four regions termed the cornu ammonis 1 to 4 (eFig. 9.104A). From the dentate gyrus, axons project to CA3 of the hippocampus. Axons from the hippocampus leave via the fornix or as Shaffer collaterals to reach CA1. Axons from CA1 may enter the fornix or project to the subiculum. Finally, axons from the subiculum enter the fornix or go back to the entorhinal cortex. A second afferent pathway from the entorhinal cortex to the hippocampal formation is through the alvear pathway. Axons in the alvear pathway project directly on to CA1 and CA3 of the hippocampus (eFig. 9.104B). Similar to the perforant pathway, axons leaving the alvear pathway primarily originate from CA1 and CA3, which then project to the subiculum. Efferent axons leaving the hippocampal formation primarily exit from the subiculum and form the fornix (Latin for “arch”), a white matter structure that arches over the ventricular system (eFig. 9.95). The fornix begins with axons exiting the hippocampus to form the alveus along the ventricular surface of the hippocampus. As the axons come together medially, they form a bundle referred to as the fimbria of the fornix. The fornix then emerges from the hippocampal formation and curves under the corpus callosum before coursing medially to run adjacent to the midline (eFig. 9.105). At the anterior commissure, the fornix divides into a precommissural fornix and postcommissural fornix to reach the nucleus accumbens, septal nuclei, medial frontal cortex, mammillary nucleus, ventromedial nucleus of the hypothalamus, and anterior nucleus of the dorsal thalamus (eFig. 9.95).

Through this section we have described a collection of anatomical structures and defined their connections with other areas of the brain and brainstem without exploring how these individual structures are interconnected with one another. In the 1930s James Papez, an American neurologist, described a circuit that links these structures and cortical areas together in a way that was thought to be involved in the experience and expression of emotion. This is referred to as the Papez circuit (eFig. 9.106). The circuit begins with fibers from the subiculum, which then enter the fornix to reach the mammillary nuclei. These axons then project through the mammillothalamic tract to the anterior nucleus of the thalamus. Next, the axons from the anterior nucleus of the thalamus project through the internal capsule to the cingulate gyrus. Lastly, the cingulum fibers from the cingulate cortex project to the parahippocampal gyrus and then the entorhinal cortex and hippocampal formation (eFig. 9.106). Papez’s description of this circuit is useful for reviewing the major limbic system pathways; however, the role of some of the structures in the pathway has been shown to play little or no role in the expression of emotion. In addition, many of the structures that do play a role in the expression of emotion also have a role in other functions.