Special Senses

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Chapter 12 Special Senses

The special senses of olfaction, vision, taste, hearing and balance are conveyed to the brain in cranial nerves. In each case, highly specialized peripheral receptors respond to stimuli in the external environment or our relationship to it. The olfactory system has an ancient lineage, reflected by the fact that afferent olfactory pathways proceed directly to the cerebral cortex and bypass the thalamus. Its terminal fields are, likewise, primitive cortical areas in a phylogenetic sense and are considered to be parts of the limbic system. All other special senses have a thalamic representation that projects to specialized regions of the neocortex. The integrative functions related to the various special senses (e.g. control of ocular gaze) are also included here. Of particular importance is a detailed discussion of retinal functional anatomy.

Olfaction

Olfactory pathways subserving the sense of smell are described in this section. Details of the relationship between the olfactory pathways and the limbic system are shown in Figure 16.7.

The olfactory nerves arise from olfactory receptor neurones in the olfactory mucosa. The axons collect into approximately 20 bundles and enter the anterior cranial fossa by passing through the foramina in the cribriform plate. They attach to the inferior surface of the olfactory bulb, which is situated at the anterior end of the olfactory sulcus on the orbital surface of the frontal lobe, and terminate in the bulb. Apparently unique in the nervous system, olfactory receptor neurones are continually replaced throughout life by differentiation of stem cells in the olfactory mucosa. The olfactory bulb is continuous posteriorly with the olfactory tract, through which the output of the bulb passes directly to the olfactory cortex.

There is a clear laminar structure in the olfactory bulb (Fig. 12.1). From the surface inward, the laminae are the olfactory nerve layer, glomerular layer, external plexiform layer, mitral cell layer, internal plexiform layer and granule cell layer.

Fig. 12.1 Organization of the olfactory bulb. The radial organization of the bulb into ‘layers,’ with their principal neurone types, and an indication of their main connections are shown. Red, mitral and tufted neurones and their processes; light blue, internal granule neurones; dark blue, dopaminergic periglomerular neurones; black, olfactory receptor neurones and their processes. The olfactory tract consists of (1) centripetal axons of mitral and tufted cells, some of which synapse with neurones in the anterior olfactory nucleus, and (2) centrifugal axons (yellow), which terminate in the different zones indicated.

The olfactory nerve layer consists of unmyelinated axons of the olfactory neurones. The continuous turnover of receptor cells means that axons in this layer are at different stages of growth, maturity or degeneration. The glomerular layer consists of a thin sheet of glomeruli, where the incoming olfactory axons divide and synapse on terminal dendrites of secondary olfactory neurones—that is, mitral, tufted and periglomerular cells. The external plexiform layer contains the principal and secondary dendrites of mitral and tufted cells. The mitral cell layer is a thin sheet composed of the cell bodies of mitral cells, each of which sends a single principal dendrite to a glomerulus, secondary dendrites to the external plexiform layer and a single axon to the olfactory tract. It also contains a few granule cell bodies. The internal plexiform layer contains axons, recurrent and deep collaterals of mitral and tufted cells and granule cell bodies. The granule cell layer contains the majority of the granule cells and their superficial and deep processes, together with numerous centripetal and centrifugal nerve fibres that pass through the layer.

The principal neurones in the olfactory bulb are the mitral and tufted cells; their axons form its output via the olfactory tract. These cells are morphologically similar, and most use an excitatory amino acid, probably glutamate or aspartate, as their neurotransmitter. The mitral cell spans the layers of the bulb and receives the sensory input superficially at its glomerular tuft. The axons of mitral and tufted cells appear to be parallel output pathways from the olfactory bulb. It is not known whether they receive inputs from different olfactory sensory neurones.

The main types of intrinsic neurones in the olfactory bulb are periglomerular cells and granule cells. The majority of periglomerular cells are dopaminergic (cell group A15); some are GABAergic. Their axons are distributed laterally and terminate within extraglomerular regions. Granule cells are similar in size to periglomerular cells. Their most characteristic feature is the absence of an axon, hence their resemblance to amacrine cells in the retina. Granule cells have two principal spine-bearing dendrites that pass radially in the bulb to ramify and terminate in the external plexiform layer. They appear to be GABAergic. The granule cell is likely to be a powerful inhibitory influence on the output neurones of the olfactory bulb.

Centrifugal inputs to the olfactory bulb arise from a variety of central sites. Neurones of the anterior olfactory nucleus and collaterals of pyramidal neurones in the olfactory cortex project to the granule cells of the olfactory bulb. Cholinergic neurones in the horizontal limb nucleus of the diagonal band of Broca, part of the basal forebrain cholinergic system, project to the granule cell layer and also to the glomerular layer. Other afferents to the granule cell layer and the glomeruli arise from the pontine locus coeruleus and the mesencephalic raphe nucleus.

The olfactory tract leaves the posterior pole of the olfactory bulb to run along the olfactory sulcus on the orbital surface of the frontal lobe (see Fig. 16.7). The granule cell layer of the bulb is extended into the olfactory tract as scattered medium-sized multipolar neurones that constitute the anterior olfactory nucleus. They continue into the olfactory striae and trigone to the grey matter of the prepiriform cortex, anterior perforated substance and precommissural septal areas. Many centripetal axons from mitral and tufted cells relay in, or give collaterals to, the anterior olfactory nucleus; the axons from the nucleus continue with the remaining direct fibres from the bulb into the olfactory striae.

As the olfactory tract approaches the anterior perforated substance, it flattens and splays as the olfactory trigone. Fibres of the tract continue from the caudal angles of the trigone as diverging medial and lateral olfactory striae, which border the anterior perforated substance. An intermediate stria sometimes passes from the centre of the trigone to end in a small olfactory tubercle. The lateral olfactory stria follows the anterolateral margin of the anterior perforated substance to the limen insulae, where it bends posteromedially to merge with an elevated region, the gyrus semilunaris, at the rostral margin of the uncus in the temporal lobe (see Fig. 16.7). The lateral olfactory gyrus forms a tenuous grey layer covering the lateral olfactory stria; it merges laterally with the gyrus ambiens, part of the limen insulae. The lateral olfactory gyrus and gyrus ambiens form the prepiriform region of the cortex, passing caudally into the entorhinal area of the parahippocampal gyrus. The prepiriform and periamygdaloid regions and the entorhinal area (area 28) together make up the piriform cortex. The medial olfactory stria, covered thinly by the grey matter of the medial olfactory gyrus, passes medially along the rostral boundary of the anterior perforated substance toward the medial continuation of the diagonal band of Broca. Together, they curve up on the medial aspect of the hemisphere, anterior to the attachment of the lamina terminalis. The diagonal band enters the paraterminal gyrus. The medial stria becomes indistinct as it approaches the boundary zone, which includes the paraterminal gyrus, parolfactory gyrus and, between them, prehippocampal rudiment (see Fig. 16.7).

The olfactory cortex receives a direct input from the olfactory bulb, which arrives via the olfactory tract without relay in the thalamus. The largest cortical olfactory area is the piriform cortex. The anterior olfactory nucleus, olfactory tubercle, regions of the entorhinal and insular cortex and amygdala also receive direct projections from the olfactory bulb.

The entorhinal cortex (Brodmann’s area 28) is the most posterior part of the piriform cortex and is divided into medial and lateral areas (areas 28a and 28b). The lateral parts receive fibres mainly from the olfactory bulb and also from the piriform and periamygdaloid cortices.

Projections from the piriform olfactory cortex are widespread and include the neocortex (especially the orbitofrontal cortex), thalamus (especially the medial dorsal thalamic nucleus), hypothalamus, amygdala and hippocampal formation.

Vision

Eye

The eyeball, the peripheral organ of vision, is situated in the orbit, a skeletal cavity whose walls help protect the eye from injury (Fig. 12.2). The orbit also has a more fundamental role in the visual process itself: it provides rigid support and direction to the eye and forms the sites of attachment for its external muscles. This setting permits the accurate positioning of the visual axis under neuromuscular control and determines the spatial relationship between the two eyes—essential for binocular vision and conjugate eye movements.

Fig. 12.2 The organization of the eye, viewed from above. In this illustration, the left eye and part of the lower eyelid are depicted in horizontal section and also cut away to show internal structure.

The eyeball is embedded in orbital fat, separated from it by a thin fascial sheath. It is composed of the segments of two spheres of different radii. The anterior segment, part of the smaller sphere, is transparent and forms approximately 7% of the surface of the whole globe. It is more prominent than the posterior segment, which is part of the larger sphere and opaque and forms the remainder of the globe. The anterior segment is bounded by the cornea and the lens and is incompletely subdivided into anterior and posterior chambers by the iris. These chambers are continuous through the pupil. The anterior chamber is slightly overlapped by the sclera peripherally. The angle between the iris and cornea, therefore, forms an anulus of greater diameter than the limbus, the junction between the sclera and the cornea. The difference between these two varies from 1 to 2 mm, the angle being deeper above and below than at the sides of the eyeball. The posterior chamber lies between the posterior surface of the iris and the anterior aspect of the lens and its supporting ligament, the zonule, and is triangular in section. The apex of the triangle is the point where the iris touches the lens; the base, or zonular region, extends among the collagenous bundles of the zonule, sometimes even into a retrozonular space between the zonule and the vitreous humour in the posterior segment of the eyeball. The posterior segment consists of the parts of the eye posterior to the zonule and lens.

The anterior pole is the centre of the anterior (corneal) curvature, and the posterior pole is the centre of its posterior (scleral) curvature; a line joining these two points forms the optic axis. (By the same convention, the eye has an equator, equidistant between the poles: any circumferential line joining the poles is a meridian.) The optic axes of the two eyes, in their primary position, are parallel and do not correspond with the orbital axes, which diverge anterolaterally at a marked angle to each other. The optic nerves follow the orbital axes and are therefore not parallel; each enters its eye approximately 3 mm medial (nasal) to the posterior pole.

Visual Pathway

The visual pathway is illustrated in Figure 12.3. The first-order neurone of the visual system is a bipolar cell that is contained entirely within the retina. The second-order neurone is a ganglion cell whose axon enters the optic nerve.

Fig. 12.3 The visual pathway, showing the spatial arrangement of neurones and their fibres in relation to the quadrants of the retinae and visual fields. The proportions at various levels are not exactly to scale; in particular, the macula is exaggerated in size in the visual fields and retinae. In each quadrant of the visual field and the parts of the visual pathway subserving it, two shades of the respective colour are used—paler for the peripheral fields, and darker for the macular part of the quadrant. From the optic tract onward, these two shades are both more saturated to denote the intermixture of neurones from both retinae, with the palest shade reserved for parts of the visual pathway concerned with monocular vision. The pathway subserving the pupillary light reflex is also indicated.

The optic nerves pass posteromedially into the cranial cavity and meet in the midline, forming the optic chiasma, a flat mass of decussating fibres that lies at the junction of the anterior wall and floor of the third ventricle. The tuber cinereum and infundibulum lie posterior to the chiasma, and the third ventricle is dorsal to them. The termination of the internal carotid artery and the anterior perforated substance are lateral relations. The optic recess of the third ventricle passes over its superior surface to reach the lamina terminalis.

Optic nerve fibres arising from the nasal half of each retina, including half of the macula, cross in the chiasma to enter the contralateral optic tract. Fibres from the temporal hemiretinae continue into the ipsilateral optic tract. Decussating fibres loop a little backward into their ipsilateral optic nerve before crossing and then passing forward into the contralateral optic tract. Macular fibres, and those from an adjacent central area, occupy almost two-thirds of the central chiasma, dorsal to all peripheral decussating fibres. The most ventral axons are nasal fibres concerned with monocular fringes of the binocular field. They lie beneath fibres from the extramacular parts of both nasal hemiretinae, which occupy an intermediate position in the chiasma.

The optic chiasma is supplied with blood from a pial plexus that receives branches from the superior hypophysial, internal carotid, posterior communicating, anterior cerebral and anterior communicating arteries. The venous drainage of the chiasma is into the basal and anterior cerebral venous system.

Behind the optic chiasma, the optic tracts diverge dorsolaterally, each passing between the anterior perforated substance and tuber cinereum. The tract curves around the cerebral peduncle, to which it adheres. Optic tract fibres terminate primarily in the lateral geniculate nucleus of the thalamus, but also in the superior colliculus, pretectal area, suprachiasmatic nucleus of the hypothalamus and inferior pulvinar.

Axons from third-order visual neurones in the lateral geniculate nucleus run in the retrolenticular part of the internal capsule and form the optic radiation, which curves dorsomedially to the occipital cortex. Fibres representing the lower half of the visual field sweep superiorly to reach the visual cortex above the calcarine sulcus. Those representing the upper half of the visual field curve inferiorly into the temporal lobe (Meyer’s loop) before reaching the visual cortex below the calcarine sulcus.

Some neurones in the occipital cortex send descending axons to the superior colliculus, which therefore receives cortical and retinal afferents. From there, fibres travel by tectobulbar tracts to motor nuclei of the third, fourth, sixth and eleventh cranial nerves and the ventral horn of the spinal cord.

Retina

The retina is the sensory neural layer of the eyeball (Figs 12.4–12.6). It is a very complex structure and should be considered a special area of the brain, from which it is derived by outgrowth from the diencephalon (Ch. 15). It is dedicated to the detection and early analysis of visual information and is an integrated part of the much larger apparatus of visual analysis present in the thalamus, cortex and other areas of the central nervous system.

Fig. 12.4 Ophthalmoscopic photographs of the right human retina. A, Note the dichotomous branching of vessels. Arteries are brighter red and show a more pronounced ‘reflex’ to light, as a pale stria along their length. The veins are also larger in calibre; more of them cross arteries superficially than is usual. The optic disc, around the entry of the vessels, is a light pink, with a surrounding zone of heavier pigmentation. Compare with Figure 12.5A from the same Caucasian adult. B, Appearances in a heavily pigmented individual (an adult of African origin), with a paler optic disc than in A. Note accentuation of the edge of the disc by retinal and choroidal pigmentation. The arteries cross the veins superficially in this retina. C, Normal macula of a young Caucasian subject. The vessels radiate from the centrally placed fovea. The macular branches of the central retinal artery are approaching from the right. The macula is largely free of vessels of macroscopic size, but the capillaries here form a particularly close network, except at the fovea. D, The region of the optic disc in an eye with poorly developed pigmentation. Three cilioretinal arteries are curving around the edge of the disc (two on the left, one on the right). Between the two cilioretinal arteries, a single macular artery is apparent. Due to the depressed pigmentation, choroidal vessels are also visible, especially veins; on the left of the photograph, two large vorticose venous tributaries can be seen.

Fig. 12.5 Fluorescence angiograms of the retina. These are produced by photography with a fundus camera at known periods of time following the introduction of fluorescein into the circulation. A, Angiogram of the same retina shown in Figure 12.4A, taken in ‘mid-venous’ phase. The arteries display an even fluorescence, but the veins appear striped, owing to laminar flow. This appearance is the reverse of the arterial ‘reflex’ shown in Figure 12.4A and should not be compared with it. The background mottling is due to fluorescence from the choroidal vessels. B, Angiogram of the left optic disc, showing the major arteries and veins and also their smaller branches. Note particularly the radial pattern in the retinal capillaries. The laminar flow in the veins is less obvious than in Figure 12.4A. C, Angiogram showing the macular region of a right eye. The main macular vessels are approaching from the right. The subject is an elderly person with considerable macular pigmentation, which masks fluorescence from the choroidal circulation. D, Angiogram of the macula of a young subject (left eye) showing the macular capillaries in detail. Note the central avascular fovea. Compare with C.

Fig. 12.6 Section through the fovea centralis.

(By permission from Young, B., Heath, J.W., 2000. Wheater’s Functional Histology, Churchill Livingstone, Edinburgh.)

The retina lies between the choroid externally and the vitreous body internally. It is thin, being thickest (0.56 mm) near the optic disc; it diminishes to 0.1 mm anterior to the equator and continues at this thickness to the ora serrata. It also thins locally at the fovea of the macula. The retina is continuous with the optic nerve at the optic disc. Anteriorly, at the ora serrata, a thin, non-neural prolongation of the retina extends forward over the ciliary processes and iris as the ciliary and iridial parts of the retina, respectively; they consist of pigmented and columnar epithelial layers only. The optic part of the retina extends from the optic disc to the ora serrata. It is soft, translucent and purple in the fresh, unbleached state because of the presence of rhodopsin (visual purple), but it soon becomes opaque and bleached when exposed to light.

Near the centre of the retina, there is a region 5 to 6 mm in diameter that contains the macula lutea (see Fig. 12.5C, D), an elliptical yellowish area measuring approximately 2 mm horizontally and 1 mm vertically. Its colour is due to the presence of xanthophyll derivatives. The macula lutea contains a central depression, the fovea centralis or foveola, with a diameter of approximately 0.4 mm, where visual resolution is highest (see Fig. 12.6.) Here, all elements except pigment epithelium cone photoreceptors are displaced laterally. The minute size of the foveola is the reason why the visual axes must be directed with great accuracy to achieve the most discriminative vision.

About 3 mm medial (nasal) and 1 mm superior to the foveola, the optic nerve becomes continuous with the retina at the optic disc (‘blind spot’). It is approximately 1.5 mm in diameter. The name ‘optic papilla,’ which is often applied to the disc, is a misnomer because almost all of a normal disc is level with the retina. Centrally, it contains a shallow depression, where it is pierced by the central retinal vessels (see Figs 12.2, 12.4, 12.5A, B). The disc is devoid of photoreceptors and is therefore insensitive to light. By ophthalmoscopy, the disc is normally pink, but it is much paler than the retina and may be grey or almost white. In optic atrophy the capillary vessels disappear, and the disc is then white.

Microstructure

The retina is derived from the two layers of the invaginated optic vesicle; the outer layer becomes the layer of pigment cells, and the inner layer develops into a complex multilaminar structure of sensory and neural cells. Anteriorly, sensory and neural cells are absent from the retina as it approaches the ora serrata and merges into the ciliary body and iris.

The neural retina contains a variety of cell types, including photoreceptors (rod and cone cells), their first-order neurones (bipolar cells) and the somata and axons of the second-order neurones (ganglion cells); it also contains two major classes of interneurones, the horizontal and amacrine cells. In addition, the retina contains neuroglial elements and a rich vascular system, chiefly of capillaries. It is backed by specialized pigment epithelial cells.

Layers of the Retina

The retina is organized into layers or zones (Fig. 12.7), where distinctive components of its cells are clustered together or in register to form continuous strata. These layers extend uninterrupted throughout the photoreceptive retina except at the exit point of the optic nerve fibres at the optic disc, although certain layers are much reduced at the foveola where the photoreceptive elements predominate. The names given to the different layers reflect, in part, the components present within them, and also their position in the thickness of the retina. Conventionally, those structures farthest from the vitreous (i.e. toward the choroid) are designated as outer or external, and those toward the vitreous are inner or internal.

Fig. 12.7 Retina of a 60-year-old man. The section was made close to the optic nerve head, explaining the thickened nerve fibre layer. 1, pigment epithelial layer; 2, rod and cone layer; 3, external limiting membrane; 4, outer nuclear layer; 5, outer plexiform layer; 6, inner nuclear layer; 7, inner plexiform layer; 8, ganglion cell layer; 9, nerve fibre layer; 10, internal limiting membrane; 11, choroid; 12, sclera.

(Courtesy of the late Gordon L. Ruskell, Department of Optometry and Visual Science, The City University, London.)

Customarily, 10 retinal layers are distinguished (Fig. 12.8), beginning at the choroidal edge and passing toward the vitreous. These are the retinal pigment epithelium, layer of rods and cones (outer and inner segments), external limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fibre layer, and internal limiting membrane. Some of these are subdivided into substrata, and an innermost plexiform layer between layers 8 and 9 has also been demonstrated.

Fig. 12.8 Layered arrangement of neuronal cell bodies in the retina and the interconnections of their processes in the intervening plexiform layers. Also shown are the two principal types of neuroglial cells in the retina; microglia are also present but are not shown.

Rod and cone cells reach radially inward from the rod and cone lamina through the outer nuclear layer, where they have their nuclei, to the outer plexiform layer, where they synapse with bipolar and horizontal cells. Bipolar cells possess dendrites in the outer plexiform layer, cell bodies and nuclei in the inner nuclear layer, and axons in the inner plexiform layer, where they synapse with ganglion cell and amacrine cell dendrites. Horizontal cells have their dendrites and axons in the outer plexiform layer and their nuclei in the inner nuclear layer; ganglion cells have their dendrites in the inner plexiform layer, their cell bodies in the ganglion cell layer and their axons in the layer of nerve fibres (and within the optic nerve). Amacrine cell dendrites are mainly in the inner plexiform layer, although some (interplexiform cells) extend into the outer plexiform layer; amacrine cell dendrites are situated in either the inner nuclear layer or the outer part of the ganglionic layer (displaced amacrines). Pigment cells lie behind the retina, and several types of retinal glial cell are distributed in distinctive locations among its different layers.

The composition of the retinal layers is as follows:

Cells of the Retina

Retinal Pigment Epithelial Cells

The retinal pigment epithelial cells are low cuboidal cells that form a single continuous layer, extending from the periphery of the optic disc to the ora serrata and continue from there into the ciliary epithelium. They are flat in radial section and hexagonal or pentagonal in surface view. There are about 4 million to 6 million in the human retina. Their cytoplasm contains numerous melanin granules (Fig. 12.9). Apically (toward the rods and cones), the cells bear long (5 to 7 mm) microvilli that contact or project between the outer ends of rod and cone processes. The tips of rod outer segments are deeply inserted into invaginations in the apical membrane. The attachments are unsupported by junctional complexes and are broken in the clinical condition of retinal detachment arising from trauma or disease processes.

Fig. 12.9 Unstained retinal pigment epithelium from a 40-year-old individual, seen in surface view.

(Courtesy of John Marshall, Institute of Ophthalmology, London.)

Pigment epithelial cells play a major role in the turnover of rod and cone photoreceptive components. Their cytoplasm contains the phagocytosed ends of rods and cones undergoing lysosomal destruction. The final products of this process are lipofuscin granules, which accumulate in these cells and add to their granular appearance. The failure of some part of this process may cause progressive loss of retinal function and eventual blindness, such as when enzyme deficiencies cause the buildup of shed but undegraded photoreceptor components within the retina.

The epithelium also acts as an antireflection device and prevents the light from bouncing back into the photoreceptive layer, with consequent loss of image sharpness. This process is complex, because the energy absorbed can be dissipated as heat or generate free radicals, both of which are potentially damaging. Indeed, very intense light may damage the pigment cells and cause epithelial breakdown.

The zone of tight junctions between the pigment cells allows the epithelium to function as an important blood–retinal barrier between the retina and the vascular system of the choroid. These junctions guard the special ionic environment of the retina and inhibit the entry of leukocytes into this immunologically sequestered compartment of the eye.

Cone and Rod Cells

The cone and rod cells are the retinal photoreceptor cells (Fig. 12.10). They are long, radially oriented structures with a cylindrical photoreceptive portion at the end nearest to the pigment epithelium and synaptic contacts at the other end, within the outer plexiform layer. Both types of cells have a similar organization, although their details differ. From the external (choroidal) end inward, the cells consist of outer and inner segments, a cell body containing the nucleus and either a cone pedicle or a rod spherule (depending on cell type); this is an area of synaptic contact with adjacent bipolar and horizontal cells and with other cone or rod cells. The outer and inner segments together form a cone process or a rod process (it should be noted that the terms cone and rod are often loosely applied to the whole cell); the cone process is wider but tapers (hence the name), whereas the rod processes are cylindrical. The outer and inner segments are connected by a short cilium.

Fig. 12.10 Major features of a retinal rod cell (A) and a retinal cone cell (B). Note that the relative size of the pigment epithelial cells has been exaggerated for illustrative purposes.

Cone cells are chiefly responsible for high spatial resolution and colour vision in good lighting conditions (photopic vision). Rod cells provide high monochromatic sensitivity to a much wider range of illumination down to much lower intensities (scotopic vision), although with relatively low spatial discrimination because of their different neural connections. Cone cells are of three types—red, green and blue—according to their maximal spectral sensitivities. They are highly concentrated in the centre of the retina (the fovea), where visual acuity is greatest, but they populate the whole retina, intermingled with rods, as far as its neural edge. Rods are excluded from the fovea. The total number of rods in the human retina has been estimated at 110 million to 125 million, and cones at 63 million to 68 million (Osterberg 1935).

The outer segments of rods contain the photoreceptive protein rhodopsin (visual purple). Related photosensitive pigments with different absorption properties are present in cones. Photoreceptive pigments are incorporated into flattened membranous discs that form as deep infoldings of the plasma membrane and stack together within the photoreceptor outer segments. They bud off as free discs within the outer segment of rods, where their turnover is rapid. New discs are generated at the proximal end closest to the soma and they are shed at the distal end embedded in the pigment epithelium, where they are phagocytosed. Turnover appears to be less rapid in cones, where the discs retain continuity with the plasma membrane, and a more random insertion of disc components may occur. Cones are much narrower at the fovea, where they closely resemble rods in size.

Bipolar Cells

Bipolar cells are radially oriented neurones, each with one or more dendrites that synapse with cones or rods and horizontal cells and interplexiform cells in the outer plexiform layer. Their somata are located in the inner nuclear layer, and axonal branches given off in the inner plexiform layer synapse with dendrites of ganglion cells or amacrine cells (see Fig. 12.8). Cone bipolars are of three major types—midget, blue cone or diffuse—according to their connectivity and size. As their name implies, midget cone bipolars are small cells, and each one is part of a single one-to-one channel from cone to ganglion cell; they are thought to mediate high spatial resolution. Blue cones have similar connectivity and selectively form part of a short wavelength-mediating channel. The larger diffuse cone bipolars are connected to up to 10 cones and are thought to signal luminosity rather than colour. Rod bipolars receive direct photoreceptive inputs from many rods and relate to ganglion cells indirectly via a synapse with amacrine cells.

Horizontal Cells

Horizontal cells (see Fig. 12.8) are inhibitory interneurones whose dendrites and axons extend within the outer plexiform layer, making synaptic contacts with the bases of cones and rods and, via gap junctions at the tips of their dendrites, with one another. Their cell bodies lie in the outer part of the inner nuclear layer. Because of their interactions with photoreceptor cells and bipolar cells, horizontal cells create inhibitory surrounds. When illumination of a photoreceptor cluster with a point of light causes depolarization of synaptically connected ‘on’ bipolars at its bright centre, horizontal cell dendrites cause inhibition at the edge of the illuminated area, thus sharpening contrast and maximizing spatial resolution.

Amacrine Cells

Amacrine cells (see Fig. 12.8) lack typical axons, but their dendrites function as axons and dendrites and make both incoming and outgoing synapses. Each neurone has a cell body in the inner nuclear layer; near its boundary with the inner plexiform layer; or on the outer aspect of the ganglion cell layer, where they are known as displaced amacrine cells. The processes of amacrine neurones make scattered chemical synaptic contacts with the axons of bipolar cells, dendrites (and possibly axons) of ganglion cells and the processes of other amacrine cells. They also receive numerous synapses from bipolar cells. Some amacrine cells form electrical synapses with bipolar cells.

There are several classes of amacrine cells that variously serve a number of important functions in vision. One class (amacrine II cells) transmits signals from rod bipolars to ganglion cells and is therefore an essential element in the rod pathway. Others appear to be important modulators of photoreceptive signals and serve to adjust or maintain relative colour and luminosity inputs under changing light conditions, such as at different times of the day. They are probably responsible for some of the complex forms of image analysis known to occur within the retina (e.g. directional movement detection).

Ganglion Cells

Ganglion cells (see Fig. 12.8) are the final common pathway neurones of the retina. Their dendrites are synaptically connected with processes of bipolar and amacrine neurones in the inner plexiform layer, and their axons are likewise connected with neurones in the central nervous system. Their axons form the layer of nerve fibres on the inner surface of the retina. They turn tangentially to the optic disc, through which they leave the eye as fibres of the optic nerve. The axons are subsequently distributed to various parts of the brain, including the lateral geniculate nucleus, pretectal area and superior colliculus of the midbrain; the thalamic pulvinar; and the accessory optic system.

Ganglion cell bodies form a single stratum in most of the retina but become progressively more numerous near the macula. They are ranked in about 10 rows in the macular area, and their number diminishes again toward the fovea, from which they are almost totally excluded. Ganglion cells are multipolar neurones, varying from 10 to 30 mm or more in diameter. Their dendrites vary in number and branching pattern and usually emerge opposite the axon. Numbers of ganglion cells in the human macular area reach 38,000/mm²; they are more numerous in the nasal than the temporal retina and in the superior retina compared with the inferior, although numbers vary considerably in different eyes. In total, each human retina has approximately 106 ganglion cells, each of which receives signals from large numbers of photoreceptor cells.

In the nerve fibre layer, axons of ganglion cells converge on the optic disc from the whole retina. They converge in a simple radial pattern from the medial (nasal) half of the retina. However, the macular area, inferolateral to the optic disc, complicates the course of the lateral (temporal) axons. Axons from the macula form a papillomacular fasciculus that passes almost straight to the disc. The more temporal fibres, which are more peripheral, swerve circumferentially above and below the macula to reach the disc.

Axons of ganglion cells are almost always non-myelinated within the retina, which is an optical advantage because myelin is refractile. They are surrounded by the processes of radial glial cells and retinal astrocytes. A few small myelinated fibres may occur, but in general, myelin sheaths usually commence only as the axons enter the optic disc to become the optic nerve.

Retinal Glial Cells

Retinal glial cells are of three types: radial (Müller) cells, astrocytes and microglia. Radial glial cells are the predominant glial element in most of the retina. Retinal astrocytes are largely confined to the ganglion cell and nerve fibre layers. Microglial cells are scattered throughout the neural part of the retina in small numbers (see Fig. 12.8).

Radial glial cells span the entire thickness of the neural retina. They ensheathe and separate the various photoreceptive and neural cells, except at synaptic sites. They form the outer boundary of the retinal tissue at the level of the inner rod and cone segments and the inner boundary at the internal limiting membrane. Their nuclei lie within the inner nuclear layer, and from this region, a single thick fibre ascends radially, giving off complex lateral lamellae that branch among the processes of the outer plexiform layer. Apically, the central process terminates in a surface from which microvilli project into the space between the rod and cone processes. Just beneath this area, the radial glial cells form a line of dense zonulae adherentes with one another and with receptor inner segments, thus forming the external limiting membrane. On the inner aspect of the retina, the main radial glial cell process expands in a terminal footplate that contacts those of neighbouring radial glial cells and astrocytes and attaches to the internal limiting membrane. Like other neuroglia, radial glia also contact blood vessels, especially capillaries, and their basal laminae fuse with those of the vascular smooth muscle in the media of larger vessels or of the endothelia lining capillaries. These extensive neuroglial cells form much of the total retinal volume and almost totally fill the extracellular space between neural elements. Their functions appear to be similar to those of astrocytes—that is, maintenance of the stability of the retinal extracellular environment by ionic transport, uptake of neurotransmitter, removal of debris, storage of glycogen, electrical insulation of receptors and neurones and mechanical support of the neural retina.

The cell bodies of retinal astrocytes lie between the layer of nerve fibres and the internal limiting membrane, while their processes branch to form sheaths around ganglion cell axons. They are present only in regions of the retina that are vascularized and are therefore absent from the fovea. Astrocytes contribute substantially to the glia limitans, which surrounds the capillaries. Retinal microglia are scattered mainly within the inner plexiform layer. Their radiating branched processes spread mainly parallel to the retinal plane, and this gives them a star-like appearance when viewed microscopically from the surface of the retina. They can act as phagocytes, and their number increases in the injured retina.

The expanded end-feet of radial glial cells and astrocytes are separated from the vitreous body by a complex, rather thick (0.5 mm) internal limiting membrane that is continuous with the internal limiting membrane of the ciliary body. The delicate collagen fibrils of the vitreous body blend with the glial basal lamina. The internal limiting membrane is involved in fluid exchange between the vitreous and the retina and, perhaps through the latter, with the choroid. It has various other functions, including anchorage of retinal glial cells and inhibition of cell migration into the vitreous body.

Modifications in the Macular Area

All the retinal layers are modified in the macular area and, to a marked degree, in the fovea, which is largely devoid of rod cells or processes. Approximately 2500 close-packed, elongated, very narrow cone cells lie in the floor of the fovea (foveola), an arrangement that favours photopic vision and the high degree of spatial discrimination typical of foveal vision.

The general displacement of the outer nuclear layer to the foveal periphery means that the internal processes of the photoreceptors are stretched out tangentially in the external plexiform layer; consequently, there are no cone pedicles or rod spherules in the central fovea and foveola. The inner nuclear layer is also displaced to the edge of the foveal depression, and the internal plexiform, ganglionic and nerve fibre layers are almost absent from the whole fovea. Therefore, even on the foveal wall, the retina is thinner and more transparent than elsewhere. Capillaries reach the foveal margin, but they invade the ganglionic layer only at its circumference, so that the fovea is normally devoid of all blood vessels.

CASE 1 Macular Degeneration

An 81-year-old patient presents with a 6-month history of increasingly blurred vision initially involving the right eye and later the left. He has observed a decreased ability to read a newspaper, especially in dim light, and difficulty with dark adaptation. He has no other significant symptoms.

On examination, visual testing reveals best corrected vision of 20/100 in the right eye and 20/70 in the left. Visual fields are full with confrontation testing and perimetry. Funduscopic examination demonstrates macular oedema, and a small haemorrhage is present on the periphery of the macula in the right eye.

A fluorescein angiogram documents leakage in the region of the macula bilaterally, and the patient is diagnosed as having the neovascular subtype of age-related macular degeneration. He is treated with laser photocoagulation, but his vision gradually deteriorates over the next several years, with 20/400 acuity in the right eye and 20/200 in the left.

Discussion: Age-related macular degeneration is the leading cause of central visual loss in patients older than 65 years. The cause is unknown. Two forms of the disorder are recognized: non-neovascular (dry) and neovascular (wet). The non-neovascular form is more common, but the neovascular form is generally more severe, with a more rapid deterioration of vision.

Optic Disc and Retinal Blood Vessels

The retina is placed between two sets of arteries and veins—the ciliary vessels of the choroid, and the branches of the central retinal vessels. It depends on both circulations because neither is sufficient by itself to maintain full visual activity in the retina. The central retinal vessels enter and leave the retina at the optic disc, which is described first; then the vessels are considered.

Optic Disc

The optic disc is the region where retinal tissues meet the neural and glial elements of the optic nerve and the connective tissues of the sclera and meninges (see Figs 12.2, 12.4, 12.5). It is the exit point for the optic nerve fibres and a point of entry and exit for the retinal circulation. It is the only site where anastomoses occur with other arteries (the posterior ciliary arteries). It is visible, by ophthalmoscopy, and is a region of much clinical importance; it is here that the central vessels can be inspected directly—the only vessels so accessible in the whole body. Oedema of the disc (papilloedema) may be the first sign of raised intracranial pressure, which is transmitted into the subarachnoid space around the optic nerve and compresses the central retinal vein where it crosses the space.

The optic disc is superomedial to the posterior pole of the eye, so it lies away from the visual axis. It is round or oval, usually approximately 1.6 mm in transverse diameter and 1.8 mm in vertical diameter, and its appearance is very variable (for details, see Jonas, Gusek and Naumann 1988). In light-skinned subjects, the general retinal hue is a bright terra-cotta red, with which the pale pink of the disc contrasts sharply; its central part is usually even paler and may be light grey. These differences are due in part to the degree of vascularization of the two regions, which is much less at the optic disc; it is also due to the total absence of choroidal or retinal pigment cells, because the retina is represented in the disc by little more than the internal limiting membrane. In subjects with strongly melanized skin, both the retina and disc are darker (see Fig. 12.4B). The optic disc does not project at all in many eyes, and rarely does it project sufficiently to justify the term papilla. It is usually a little elevated on its lateral side, where the papillomacular nerve fibres turn into the optic nerve. There is usually a slight depression where the retinal vessels traverse its centre.

Retinal Vascular Supply

The central retinal artery enters the optic nerve as a branch of the ophthalmic artery, approximately 1.2 cm behind the eyeball. It travels in the optic nerve to its head, where its fascicles traverse the lamina cribrosa. At this level, which is usually not visible with ophthalmoscopy, the central artery divides into two equal branches, superior and inferior. After a few millimetres, these divide into superior and inferior nasal branches and superior and inferior temporal branches. Each of these four branches supplies its own ‘quadrant’ of the retina, although each territory is much more than a quadrant, because the branches ramify as far as the ora serrata. Corresponding retinal veins unite to form the central retinal vein. However, the courses of the venous and arterial vessels do not correspond exactly, and arteries often cross veins, usually lying superficial to them. In severe hypertension, the arteries may press on the veins and cause visible dilatation distal to these crossings. Arterial pulsation is not visible by routine ophthalmoscopy without higher magnification.

CASE 2 Retinitis Pigmentosa

A 25-year-old man presents with symptoms of approximately 5 years’ duration. At age 18 he first noted difficulty running and unsteadiness; at that time, he demonstrated only mild gait ataxia. He has noted greater difficulty driving at might. There is no family history of secular symptoms.

Neurological examination shows gait ataxia with dysmetria and impaired limb dexterity throughout. Reflexes are generally hyperactive, but the Achilles reflexes are absent. Neuro-ophthalmological examination reveals constricted visual fields with normal visual acuity. Funduscopic examination demonstrates pigmentary changes in the retina with the appearance of bony spicules, along with narrowing of the retinal arterioles and slight pallor of the optic discs.

The electroretinogram is abnormal. An electromyogram and nerve conduction study document evidence of an axonal polyneuropathy. A diagnosis of retinitis pigmentosa (RP), associated with neuropathy and ataxia is made, subsequently supported by genetic testing. Over a period of years, the patient’s neurological abnormalities increase, with marked impairment of night vision, gradual constriction of the visual fields and ultimately decreased visual acuity. RP is characterized by progressive visual loss, especially loss of night vision. It is a heterogenous group of genetic disorders leading to the death of rod photoreceptors, frequently associated with other neurological symptoms.

Visual Field Defects

Plotting visual field loss frequently reveals the approximate location of the causative lesion in the visual pathway and sometimes its nature (Fig. 12.11). Because retinal lesions can be visualized using an ophthalmoscope, these aids might appear to be redundant, but visual field measurement is still helpful in assessing the extent of the damage and may be the key factor in confirming a diagnosis. Glaucoma serves as an example. Field defects in glaucoma, occurring as a consequence of damage to the nerve fibre bundles at the optic nerve head, may be detectable ophthalmoscopically, but confirmation of the diagnosis frequently depends on field assessment. An initial constriction of the visual field is of little clinical significance, but later defects, characteristic of the disease, consist of a scotoma between 10 and 20 degrees of the fixation area, extending upward or, less commonly, downward from the blind spot. This later elongates circumferentially along the arcuate nerve fibres and subsequently extends farther. The field defect forms a linear limit or step along the horizontal meridian nasally; the loss continues, ultimately resulting in blindness.

Fig. 12.11 Schematic diagram of the visual system, demonstrating the visual field defects associated with various lesions along the visual pathways.

From Brown, T.A., 2007. Rapid Review Physiology. Mosby, Philadelphia.

With regard to the location of lesions central to the retina, deficits in the vision of one eye are usually attributable to optic nerve lesions. Lesions of the optic chiasma, involving crossing nerve fibres, produce a bilateral field loss, as exemplified by pituitary adenoma. The tumour expands upward from the pituitary fossa, compressing the inferior midline of the chiasma, and eventually produces bitemporal hemianopia, starting with an early loss in the upper temporal quadrants. Field defects in the rare cases of optic tract lesions are distinctive. The tract contains contralateral nasal and ipsilateral temporal retinal projections, and damage causes a homonymous contralateral loss of field with substantial incongruity (dissimilar defects in the two fields). Incongruity probably results from a delay in achieving coincidence between retinal topographical projections of the two inputs of the visual pathway; as contiguous projections adjust their location, they gradually achieve coincidence. It also likely reflects the normal reorganization of fibres that occurs in the optic tracts, as some fibres leave the tract in the superior brachium and others progress to the lateral geniculate nucleus. The two defective fields may display incongruity as a result of lesions above the level of the chiasma. Incongruity is most marked in optic tract defects, less obvious in optic radiation defects and usually absent in cortically induced field defects, thus providing an additional clue to the location of the cause.

Lesions of the optic radiations are usually unilateral and commonly vascular in origin. Field defects therefore develop abruptly, in contrast to the slow progression of defects associated with tumours. Resulting hemifield loss follows the general rule that visual field defects central to the chiasma (i.e behind the chiasma) are on the side opposite the lesion. Little or no incongruity is seen in visual cortical lesions, but they commonly display the phenomenon of macular sparing, with the central 5 degrees to 10 degrees field retained in an otherwise hemianopic defect.

CASE 3 Optic Neuritis

A 26-year-old woman presents with a 2-day history of progressive loss of vision in her left eye, with accompanying left orbital pain, especially on eye movement. At the onset she noted blurring of vision. She performed a monocular cover test on herself and discovered that the blurring was confined to the left eye. She noted that when she looked at a computer screen with her left eye it became ‘black and white.’ Her visual loss stabilized after several days; she ultimately observed that she could see ‘all around’ a central visual loss in the left eye. It is noteworthy that 1 year before she had an episode of numbness and tingling sensations affecting her left arm and leg, lasting about 6 weeks. She did not seek medical attention at that time.

Examination shows a visual acuity of 20/20 on the right and 20/400 on the left. Impaired colour vision is noted on the left, and there is a central scotoma with visual field testing. There is a prominent left afferent pupillary defect (Marcus Gunn pupil). The fundi are normal, and extraocular motility is full, with the exception of occasional square wave jerks.

Magnetic resonance imaging (MRI) with and without gadolinium shows an area of increased signal intensity on T2 images in the left optic nerve, as well as scattered areas of increased signal intensity in the periventricular white matter. Lumbar puncture demonstrates a mild lymphocyte pleocytosis, with slight elevation of the protein content. Monoclonal antibodies are present.

Discussion: Progressive loss of central and colour vision over several days in association with orbital pain and normal fundi points to a left retro-orbital optic neuropathy, with clinical features of a Marcus Gunn pupil. Acutely there may be disc swelling and, with time, disc pallor may occur. These findings associated with aterial attenuation suggest acute ischemic optic neuropathy (Fig. 12.12). The observation of a central scotoma with intact peripheral visual fields emphasizes that about 90% of the axons in the optic nerve subserve macular vision.

Fig. 12.12 Ischaemic optic neuritis. The optic disc is pale and mildly swollen, and there is attenuation of some of the retinal vessels.

Retrobulbar optic neuritis in a patient with a history of a hemisensory disturbance and an MRI demonstrating areas of increased signal intensity on T2 images in the periventricular white matter points strongly to a diagnosis of multiple sclerosis. Other disorders that can present with the same clinical and radiological features, such as systemic lupus erythematosus, must be excluded with appropriate testing.

CASE 4 Superior Visual Field Disturbance

A 36-year-old woman with poorly controlled partial seizures, despite taking a variety of anticonvulsant medications, undergoes a right temporal lobectomy to remove an epileptogenic focus that was identified and localized by corticography. There is evidence of mesial temporal sclerosis on MRI. Following surgery, antiepileptic medication is resumed, and the woman’s seizure disorder is completely controlled for the first time in 20 years.

Two months later, a routine ophthalmological examination demonstrates a left superior visual field defect to confrontation testing. Subsequent formal visual testing of the left eye reveals a wedge-shaped superior temporal field defect of about 20 degrees of arc and abutting the vertical meridian. In the right eye, a superior nasal field defect of about 40 degrees of arc is also present abutting the vertical meridian. The patient is unaware of the visual disturbance. The remainder of the neurological examination is normal.

Discussion: The ‘pie in the sky’ or wedge-shaped visual field defect noted in this patient is not uncommon following temporal lobectomy for epilepsy. Rostral geniculocalcarine pathway lesions produce incongruous visual field defects—that is, defects that are not exactly the same in both eyes—because geniculocalcarine fibres from corresponding retinal areas are not anatomically in close proximity until reaching the occipital lobe. Occipital lobe lesions, in contrast, produce congruous (i.e. identical) field defects that can be quadrantal. Because of the anatomical inversion of the visual pathways, inferiorly placed lesions in the optic tract or calcarine cortex tend to produce superior quadrantal defects, whereas inferior defects are consistent with lesions in the parietal lobe involving the tract from above. This case also demonstrates that visual field disturbances, particularly in the superior field, may go unnoticed by the patient. (See Fig. 12.11, optic radiation, lower division.)

CASE 5 Homonymous Hemianopia

A 34-year-old, primarily healthy woman with a 2-week history of non-radiating neck pain has had three chiropractic treatments. On the drive home from the third treatment she notices that she cannot see well to the right; the next day her ophthalmologist notes a right visual field disturbance. There is no history of prior visual symptoms, migraine or smoking. She is not using oral contraceptives. With the exception of a dense right homonymous hemianopia, the neurological examination is completely normal. The visual acuity is 20/20 bilaterally.

An initial computed tomography (CT) scan is normal, but a repeat study several days later reveals an area of hypodensity in the left occipital lobe, most likely an ischaemic infarct. MRI of the brain (without diffusion images) shows a left occipital ischaemic infarct, and a magnetic resonance arteriogram of the cervical and cranial vessels demonstrates a right vertebral artery dissection at the C1 vertebral level and occlusion of the calcarine branch of the left posterior cerebral artery. Laboratory investigations are otherwise normal.

The patient is started on anticoagulation therapy. Follow-up assessment 4 months later documents a persistent right homonymous hemianopia, and repeat MRI of the brain reveals encephalomalacia in the left occipital lobe. Magnetic resonance angiography now demonstrates only slight irregularity of the lumen of the right vertebral artery.

Discussion: Cervical manipulation is a known risk factor for stroke. Vertebral artery dissection at the C1 level can be caused by rotation of the neck with an anatomically fixed vertebral artery.

It is noteworthy that the patient’s visual field testing showed macular sparing. For many years, there has been debate whether such macular sparing has an underlying anatomical explanation, such as bilateral cortical representation of the macula or a dual blood supply, or whether this phenomenon is merely the result of slight horizontal movement of the eyes during field testing. The most commonly accepted explanation is the latter. (See Fig. 12.11, optic radiation, both divisions.)

Neural Control of Gaze

Neural control systems are required to coordinate the movements of the eyes so that the image of the object of interest is simultaneously held on both foveae, despite movement of the object or the observer. A number of separate neural systems are involved: first, to shift gaze to the object of interest using rapid movements, called saccades; and second, to stabilize the image on the fovea either during movement of the object of interest (smooth pursuit system) or during movement of the head or body (vestibulo-ocular and optokinetic systems). Although the detailed anatomical substrates for these systems differ, they share common circuitry that lies mainly in the pons and midbrain for horizontal and vertical gaze movements, respectively (Fig. 12.13).

Fig. 12.13 Summary of eye movement control. The central drawing shows the supranuclear connections from the frontal eye field (FEF) and posterior eye field (PEF) to the superior colliculus (SC), rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and paramedian pontine reticular formation (PPRF). The FEF and SC are involved in the production of saccades, whereas the PEF is thought to be important in the production of pursuit. The drawing on the left shows the brain stem pathways for horizontal gaze. Axons from the PPRF travel to the ipsilateral abducens nucleus innervating the lateral rectus (LR). Abducens internuclear axons cross the midline and travel in the medial longitudinal fasciculus (MLF) to the portion of the oculomotor nucleus (III) innervating the medial rectus (MR) of the contralateral eye. The drawing on the right shows the brain stem pathways for vertical gaze. Important structures include the riMLF, PPRF, interstitial nucleus of Cajal (INC) and posterior commissure (PC). DLPFC, dorsolateral prefrontal cortex; IV, trochlear nucleus; NPH, nucleus prepositus hypoglossi; SEF, supplementary eye field; VI, abducens nucleus; VN, vestibular nucleus.

The common element in all types of horizontal gaze movements is the abducens nucleus. This contains motor neurones that innervate the ipsilateral lateral rectus. It also contains interneurones that project via the medial longitudinal fasciculus (MLF) to the contralateral oculomotor nucleus controlling the medial rectus. A lesion of the abducens nucleus leads to a total loss of ipsilateral horizontal conjugate gaze. A lesion of the MLF produces slowed or absent adduction of the ipsilateral eye, usually associated with jerky movements (nystagmus) of the abducting eye, a syndrome called internuclear ophthalmoplegia.

The gaze motor command involves specialized areas of the reticular formation of the brain stem that receive a variety of supranuclear inputs. The main region for horizontal gaze is the paramedian pontine reticular formation (PPRF), which is located on each side of the midline in the central paramedian part of the tegmentum and extends from the pontomedullary junction to the pontopeduncular junction. Each PPRF contains excitatory neurones that discharge at high frequencies just before and during ipsilateral saccades. Pause neurones, which are located in a midline caudal pontine nucleus called the nucleus raphe interpositus, discharge tonically except just before and during saccades. They appear to exert an inhibitory influence on the burst neurones and thus prevent extraneous saccades occurring during fixation.

The vestibular nuclei and the perihypoglossal complex (especially the nucleus prepositus hypoglossi) project directly to the abducens nuclei. These projections probably carry both smooth pursuit signals, via the cerebellum, and vestibular signals. In addition, these nuclei, via reciprocal innervation with the PPRF, contain integrator neurones that control the step change in innervation required to maintain the eccentric position of the eye against the viscoelastic forces in the orbit. These forces tend to move the eyeball back to the position of looking straight ahead (i.e. the primary position) after a saccade.

The final common pathway of vertical gaze movements is formed by the oculomotor and trochlear nuclei. The rostral interstitial nucleus of the MLF (riMLF) contains neurones that discharge in relation to up-and-down vertical saccadic movements. The riMLF projects through the posterior commissure to its equivalent on the other side of the mesencephalon, as well as directly to the oculomotor nucleus. Therefore, lesions within the posterior commissure give rise to disturbance in vertical gaze, especially up-gaze (see Ch. 10, Case 9). Lesions located more ventrally in the region of the riMLF give rise to vertical gaze disorders that may be mixed up and down or mainly down-gaze. Slightly caudal to the riMLF, and directly connected to it, lies the interstitial nucleus of Cajal. It contains neurones that appear to be involved in vertical gaze by holding the vertical pursuit.

The cerebral hemispheres are extremely important for the programming and coordination of both saccadic and pursuit conjugate eye movements. There appear to be four main cortical areas in the cerebral hemispheres involved in the generation of saccades (see Fig. 12.13): the frontal eye field, which lies laterally at the caudal end of the second frontal gyrus in the premotor cortex (Brodmann’s area 8); the supplementary eye field, which lies at the anterior region of the supplementary motor area in the first frontal gyrus (Brodmann’s area 6); the dorsolateral prefrontal cortex, which lies anterior to the frontal eye field in the second frontal gyrus (Brodmann’s area 46); and the posterior eye field, which lies in the parietal lobe, possibly in the superior part of the angular gyrus (Brodmann’s area 39), and in the adjacent lateral intraparietal sulcus. These areas are apparently interconnected and send projections to the superior colliculus and the brain stem areas controlling saccades.

It seems that there are two parallel pathways involved in the cortical generation of saccades. An anterior pathway originates in the frontal eye field and projects both directly and via the superior colliculus to the brain stem saccadic generators. This pathway also passes indirectly via the basal ganglia to the superior colliculus. Projections from the frontal cortex influence cells in the pars reticulata of the substantia nigra, via a relay in the caudate nucleus. An inhibitory pathway from the pars reticulata projects directly to the superior colliculus. This appears to be a gating circuit related to volitional saccades, especially of the memory-guided type. A posterior pathway originates in the posterior eye field and passes to the brain stem saccadic generators via the superior colliculus.

To maintain foveation of a moving target, the smooth pursuit system has developed relatively independently of the saccadic oculomotor system, although there are inevitable interconnections between the two. The first task is to identify and code the velocity and direction of a moving target. This is carried out in the extrastriate visual area known as the middle temporal visual area (also called visual area V5), which contains neurones sensitive to visual target motion. In humans, this lies immediately posterior to the ascending limb of the inferior temporal sulcus at the occipitotemporal border. The middle temporal visual area sends this motion signal to the medial superior temporal visual area, which is thought to lie superior and a little anterior to area V5 within the inferior parietal lobe. Damage to this area results in impairment of smooth pursuit of targets moving toward the damaged hemisphere.

Both the medial superior temporal visual area and the frontal eye field send direct projections to a group of nuclei that lie in the basal part of the pons. In the monkey, the dorsolateral and lateral groups of pontine nuclei receive direct cortical inputs related to smooth pursuit. Lesions of similarly located nuclei in humans result in abnormal pursuit. These nuclei transfer the pursuit signal bilaterally to the posterior vermis, contralateral flocculus and fastigial nuclei of the cerebellum. The pursuit signal ultimately passes from the cerebellum to the brain stem, specifically to the medial vestibular nucleus and nucleus propositus hypoglossi, then to the PPRF and possibly directly to the ocular motor nuclei. This circuitry therefore involves a double decussation—first at the level of the mid-pons (pontocerebellar neurones), and second in the lower pons (vestibuloabducens neurones).

The vestibulo-ocular reflex maintains coordination of vision during movement of the head. It results in a compensatory conjugate eye movement that is equal but opposite to the movement of the head. This is essentially a three-neurone arc. It consists of primary vestibular neurones that project to the vestibular nuclei, secondary neurones that project from these nuclei directly to the abducens nucleus and tertiary neurones that are abducens motor neurones.

The optokinetic response is another visually mediated reflex that stabilizes retinal imagery during rotational movement. As the visual scene changes, the eyes follow, holding the retinal image steady until they shift rapidly in the opposite direction to another area of the visual scene. The full field of vision, rather than small objects within it, is the stimulus, and the alternating slow and fast phases of movement generated describes optokinetic nystagmus. The optokinetic reflex functions in collaboration with the rotational vestibulo-ocular reflex. Because of the mechanical arrangements of the semicircular canals, in the sustained rotations of the body described earlier, the vestibulo-ocular reflex fades. In darkness, the reflex, which is initially compensatory, loses velocity, and after approximately 45 seconds, the eyes become stationary.

CASE 6 Internuclear Ophthalmoparesis

A 69-year-old woman notes the sudden onset of side-by-side double vision when looking straight ahead and to the left. She performs a monocular cover test on herself and finds that her vision is normal in each eye when uncovered. Her past history is positive for hypertension, coronary artery angioplasty and dyslipidemia.

Examination shows failure of adduction of the right eye on left gaze, with monocular nystagmus involving the left eye on left gaze. Adduction with convergence is normal bilaterally.

Discussion: Selective involvement of the right medial rectus muscle on left gaze, in association with monocular nystagmus in the right abducting eye with intact convergence, indicates a right internuclear ophthalmoparesis due to a lesion in the right medial longitudinal fasciculus (MLF), the anatomical structure interconnecting the oculomotor nuclei and the abducens nucleus and associated PPRF in the pons. This is often due to multiple sclerosis in the young and to a vascular event in the elderly. The MLF is supplied by the paramedian branches of the basilar artery; internuclear ophthalmoparesis is a relatively common result of ischaemia due to small-vessel occlusive disease.

Pupillary Light Reflex

The pupillary light reflex is a dynamic system for controlling the amount of light reaching the retina (Fig. 12.14). Illumination of the retina causes reflex constriction of the pupil (miosis). The direct component of the light reflex mediates constriction of the pupil of the ipsilateral eye, and the consensual component elicits simultaneous constriction of the contralateral pupil.

Fig. 12.14 Pupillary light reflex and accommodation reflex.

(From MacKinnon, P., Morris, J. [Eds.], 1990. Oxford Textbook of Functional Anatomy, vol 3, Head and Neck. Oxford University Press, Oxford. By permission of Oxford University Press.)

A light stimulus acting on the retinal photoreceptors gives rise to activity in retinal ganglion cells, the axons of which form the optic nerve. Activity is conducted through the optic chiasma and along the optic tract, and the majority of fibres end in the lateral geniculate nucleus of the thalamus. However, a small number of fibres leave the optic tract before it reaches the thalamus and synapse in the pretectal nucleus. The information is relayed from the pretectal nucleus by short neurones that synapse bilaterally with preganglionic parasympathetic neurones in the Edinger–Westphal nucleus of the oculomotor nerve complex in the rostral midbrain. Efferent impulses pass along parasympathetic fibres of the oculomotor nerve to the orbit, where they synapse in the ciliary ganglion. Postganglionic fibres (short ciliary nerves) pass to the eyeball to supply the sphincter pupillae, which reduce the size of the pupil when it contracts.

There is also a connection to the spinal sympathetic centre controlling the dilator pupillae. The preganglionic fibres arise from neurones in the lateral column of the first and second thoracic segments and pass via the sympathetic trunk to the superior cervical ganglion, where they synapse on postganglionic neurones. Postganglionic fibres arising from these neurones are distributed to the cavernous plexus; from there, they travel mainly through the long ciliary nerves to the anterior part of the eye, where they supply the dilator pupillae.

Because pupillary size results from the balanced action of these two innervations, the pupil dilates when the parasympathetic stimulus ceases. The pupil also dilates in response to painful stimulation of almost any part of the body. Presumably, fibres of sensory pathways connect with the sympathetic preganglionic neurones described earlier.

Accommodation Reflex

When focusing on a nearby object, the eyes converge, the lens becomes more convex and the pupils constrict (see Fig. 12.14).

Information from the retina passing to the visual cortex does not constitute the afferent limb of a simple reflex in the usual sense of the term, but it permits the visual areas to assess the clarity of objects in the visual field. Cortical efferent information passes to the pretectal area and then to the Edinger–Westphal nucleus, which contains preganglionic parasympathetic neurones whose axons travel in the oculomotor nerve. Efferent impulses pass in the oculomotor nerve to the orbit, where they synapse in the ciliary ganglion. Postganglionic fibres (short ciliary nerves) pass to the eyeball and stimulate contraction of the ciliary muscle, which slackens the ligament of the lens and increases the curvature of the lens for near vision. Contraction of the sphincter pupillae and relaxation of the dilator pupillae constrict the pupil. Simultaneously, contraction of the medial, superior and inferior recti (all innervated by the oculomotor nerve) converges the eyes on the near target. The pupillary changes may be secondary to convergence.

In certain central nervous system diseases (e.g. tabes dorsalis), the pupillary light reflex may be lost, but pupillary constriction as part of the accommodation reflex is retained (Argyll Robertson pupil). The site of a lesion producing such an effect is unclear, but it may involve the periaqueductal grey matter.

Taste

Afferent nerve fibres carrying taste information are the peripheral processes of neuronal cell bodies in the geniculate ganglion of the facial nerve and in the inferior ganglia of the glossopharyngeal and vagus nerves. Taste from the anterior two-thirds of the tongue, excluding the vallate papillae, and from the inferior surface of the palate is carried in the sensory root of the facial nerve (nervus intermedius). Taste buds in the vallate papillae, posterior third of the tongue, palatoglossal arches, oropharynx and, to some extent, palate are innervated by the glossopharyngeal nerve. Those in the extreme pharyngeal part of the tongue and the epiglottis are innervated by fibres of the vagus nerve.

On entering the brain stem, these afferent fibres constitute the tractus solitarius, and they terminate in the rostral third of the nucleus solitarius of the medulla. Second-order neurones arising from the nucleus solitarius cross the midline, and many ascend through the brain stem in the dorsomedial part of the medial lemniscus. They terminate in the medial part of the ventral posteromedial nucleus of the thalamus. From the ventral posteromedial nucleus, third-order neurones project through the internal capsule to the anteroinferior part of the sensory cortex and to the limen insulae. Other ascending projections to the hypothalamus have been described that may represent the pathway by which gustatory information reaches the limbic system.

Hearing

The primary afferents of the auditory pathway arise from cell bodies in the spiral ganglion of the cochlea (see Figs. 11.20, 11.23, 11.28, 11.31). The axons constitute the auditory component of the vestibulocochlear nerve, which enters the brain stem at the cerebellopontine angle. Afferent fibres bifurcate and terminate in the dorsal and ventral cochlear nuclei. Onward connections make up the ascending auditory pathway (Fig. 12.15). The dorsal cochlear nucleus projects via the dorsal acoustic stria to the contralateral inferior colliculus. The ventral cochlear nucleus projects via the trapezoid body or the intermediate acoustic stria to relay centres in the superior olivary complex, the nuclei of the lateral lemniscus or the inferior colliculus. The superior olivary complex is dominated by the medial superior olivary nucleus, which receives direct input from the ventral cochlear nucleus on both sides, and is involved in localization of sound by measuring the time difference between afferent impulses arriving from the two ears.