Neuro-ophthalmology: A Short Primer 61 3 Neuro-ophthalmology: A Short Primer Urs Schwarz CONTENTS every part of the brain (Fig. 3.2). Moreover, these systems are probably amongst the best investigated so 3.1 Introduction 61 far; and enormous knowledge has been amassed over 3.2 Vision and Visual Perception 61 the past few decades employing a variety of techniques 3.2.1 Receptive Fields 64 3.2.2 The Retino-geniculo-cortical Pathway 67 from single cell recordings, optical imaging, eye 3.2.2.1 The Retina 67 movement recordings, functional magnetic resonance 3.2.2.2 The Lateral Geniculate Nucleus 67 imaging, to neuropsychological examinations. In 3.2.2.3 The Primary Visual Cortex 68 addition, this research has clarifi ed many fundamental 3.2.2.4 Lesions in the Retino-geniculo-cortical Pathway 70 principles of neural and neuronal processing, which 3.2.3 The Extrastriate Visual Cortex 72 3.2.3.1 The Dorsal Pathway 72 subsequently have enriched other fi elds of brain 3.2.3.2 The Ventral Pathway 73 research as well as computational neuroscience. 3.2.4 The Accessory Optic System 74 The optomotor system provides a magnifi cent 3.3 Eye Movements 74 window into the nervous system for clinicians, as people 3.3.1 The Oculomotor Nuclei and the Extraocular suffering from even the smallest disruption soon are Muscles 74 3.3.1.1 Anatomy of the Ocular Motor Nuclei and Nerves 76 unable to pursue their regular routines. Armed with 3.3.1.2 Lesions of the Extraocular Nuclei and Nerves 78 thorough neuroanatomical and neurophysiological 3.3.2 Supranuclear Synchronization of Eye knowledge of this system’s workings, a clinician will be Movements 84 able to diagnose and localize many conditions right at 3.3.3 Gaze Holding Mechanisms 87 the bedside. 3.3.3.1 The Vestibulo-ocular Refl ex 87 3.3.3.2 The Optokinetic Refl ex 92 A systematic review bearing on the whole spectrum 3.3.3.3 Nystagmus 92 of normal and pathological visual, vestibular, and opto- 3.3.4 Gaze Shifting Mechanisms 93 motor neural processing would be more than one’s 3.3.4.1 Saccades 93 lifetime work. Hence, this improperly short primer is 3.3.4.2 Smooth Pursuit Eye Movements 97 very selective, fractional, and undeniably biased. An 3.3.4.3 Vergence 98 3.3.4.4 Fixation 98 attempt was made to seduce the reader to dive further References 98 into this fascinating realm of neuro-ophthalmology by presenting a basic framework of functional neuro- 3.1 anatomy. The basic neuroscientist will fi nd plenty in Introduction the works of Carpenter (1988), Zeki (1993), Milner and Goodale (1995), Wandell (1995), Zigmond et The spectacular symbiosis between the visual system, al. (1999), Kandel et al. (2000); the clinician, on the the vestibular system, and the optomotor system, each other hand, will fi nd more answers in the seminal of which is a miracle on its own, is able to solve oeuvres (Baloh and Honrubia 1990; Grüsser and an abundant array of amazing tasks (Fig. 3.1). In Landis 1991; Miller and Newman 1997; Huber and particular, the connection between vision and the Kömpf 1998; Leigh and Zee 1999). optomotor control is most intriguing, as the eye performs both the input and the output simultaneously. Altogether, it is not surprising that the implementation of these intricate neural networks encompasses almost 3.2 Vision and Visual Perception U. Schwarz, MD Priv.-Doz., Department of Neurology, University Hospital Light entering the eye is projected onto the retina, (USZ), Frauenklinikstrasse 26, 8091 Zürich, Switzerland where it is converted into an electrical signal by the 62 U. Schwarz vestibular tasks visual tasks unexpected disruption of posture moving target vL visual - selection surroundings internal - recognition representation F maintenance of selected egomotion gaze spatial orientation target between - self - target next - visual surroundings possible target Fig. 3.1. Optomotor tasks. The visuo-, vestibulo-, and proprioceptive-optomotor systems ensure maintenance of orientation in space as well as target selection and recognition despite a host of sensory confl icts and adversary disturbances. Its main goals are to keep the target of interest on the fovea (stabilization of gaze) and to produce an accurate internal representation of spatial relations between the visual surroundings, the target, and the self. vL, vestibular labyrinth afference supranuclear efference control SP epS sC aoS VI VI IV IV vT PPRF riMLF III III vis MLF conjugate OKR Cbl and vest vergence pvS vS NV NV gaze palsy gaze palsy diplopia inappropriate eye movements INO disintegrated eye movements saccade deficits Fig. 3.2. Synopsis of the optomotor system (modifi ed after Schwarz et al. 2000). Multisensory, visual, vestibular, and propriocep- tive (not shown) signals (afference) are cortically and subcortically integrated and guided to the supranuclear optomotor control system, which computes appropriate conjugate and vergence signals for each eye muscle and distributes them via the medial longitudinal fasciculus (MLF) to the individual oculomotor nuclei (efference). Therefore, the supranuclear control implements the fi nal common pathway for any mechanism that requests eye movements. Typical eye movement patterns due to lesions of the afferences, supranuclear control, and efferences are shown at the bottom. The exemplary scene shows the complexity of the visual computation: While smoothly following a moving visual target (vT) with the eyes, the visual surroundings (vS) is shifted in the opposite direction (evoking full fi eld stimulation) and, hence, elicits an optokinetic response (OKR). Sensory integration must solve the problem of these counteracting demands and generate appropriate signals to the supranuclear control for smooth pursuit eye movements (SP) only. pvS, peripheral vestibular system; epS, extrapyramidal system; aoS, accessory optic system; Cbl, cerebellum; NV, vestibular nucleus; PPRF, paramedian pontine reticular formation; riMLF, rostral interstitial nucleus of the MLF; III, oculomotor nucleus; IV, trochlear nucleus; VI, abducens nucleus; INO, internuclear ophthalmoplegia photoreceptors. A geometrically well-defi ned array of cross routed: Axons from the temporal half of one these highly specialized cells connects via an intrin- retina join axons from the nasal part of the other sic local network to one single ganglion cell, thus retina in the optic tract. Axons from the temporal implementing the fi rst receptive fi eld of the visual retina remain ipsilateral. Hence, visual objects in one system. Consecutively, signals of the retinal gan- hemifi eld, which are projected nasally onto the ipsi- glion cells are transmitted through their axons, which lateral retina and temporally onto the contralateral together form the optic nerve, to the optic chiasm in retina, are processed in contralateral central visual front of the pituitary stalk, where half of them are centers with information coming from both retinae. Neuro-ophthalmology: A Short Primer 63 The optic tract projects to three major subcortical 1982; Livingstone and Hubel 1988; Hubel 1988). structures: In parallel, even more specialized receptive fi elds • The pretectum controls the pupillary refl ex. sample primitive graphical properties – such as color, • The superior colliculus controls saccadic eye move- form and size, position, orientation, speed, and depth ments. and disparity – of visual objects, which, in turn, • The lateral geniculate nucleus is the major relay are transmitted to various dedicated areas in the for input to the visual cortex. extrastriate visual cortex (Brodmann areas 18, 19, and 37) (Brodmann 1909; Zeki 1993; Wandell Signals for each geniculate cell are sampled from 1995; Zilles and Clarke 1997). Each of these many a distinct ensemble of ganglion cell axons, which regions reconstructs a purpose-fi ltered map of the establishes the next layer of receptive fi elds. Finally, visual world or attended parts of it. Connected to axons emerging from the geniculate nuclei are other cortical areas, this information will be used to projected onto layer 4 of the striate (primary) visual solve such complex tasks as face recognition, target cortex (Brodmann area 17), which is located at the selection, processing of target motion and optic fl ow pole of the occipital lobe (Fig. 3.3). Here, visual patterns, computation of the direction of motion, information – already partially segregated into simple generation of eye and limb movements, and many graphical categories – is analyzed further (Marr more. In particular, L. Ungerleider and M. Mishkin rvhf bf F bs le re visual field defects F a a optic nerve b c chiasm b d Meyer's optic tract loop c LGN pulvinar d optic radiation l e V1p e f u calcarine sulcus g V1f occipital pole f Fig. 3.3. Anatomy of the retino-geniculo-cortical system and typical visual fi eld defects. Left panel. The right visual hemifi eld (rvhf) projects to the nasal portion of the right and the temporal portion of the left retina. Retinal ganglion cell axons form the optic nerve. Fibers from the nasal retinal half cross the midline in the optic chiasm and join those from the temporal retinal half of the other eye, which remain ipsilateral, in the optic tract and synapse in the superior colliculus and tectum (both not enhanced) as well as in the lateral geniculate nucleus (LGN). Axons emerging from the LGN arc around the inferior horn of the lateral ventricle, forming the optic radiation with its lowermost part called Meyer’s loop. They end at the striate visual cortex (V1). Note the overrepresentation (magnifi cation) of the foveal part (shown by the shadings in the visual hemifi eld and V1). Moreover, the visual hemifi eld is divided by the calcarine sulcus. The lower part projects above the sulcus, the upper part below it. The pulvinar of the thalamus receives its input directly from V1 (layer 5, Fig. 3.12).