Journal of Neuro-Ophthalmology, March 1996, Volume 16, Issue 1

Postgeniculate Afferent Visual System and Visual Higher Cortical Function

Journal of Neuro- Ophthalmology 16( 1): 23- 32, 1996. © 1996 Lippincott- Raven Publishers, Philadelphia Annual Review Postgeniculate Afferent Visual System and Visual Higher Cortical Function, 1994 Michael Wall, M. D. In this review of articles published in 1994, ad­vances in our knowledge of the postgeniculate vi­sual pathways- optic radiations and visual cortical areas V1- V5- are discussed. In addition, syn­dromes of visual higher cortical disturbances will be covered. The review is initially organized an­atomically by flow of sensory information ( Fig. 1) and later by topic. Basic studies continue to clarify our understand­ing of parallel distributed processing of informa­tion within parallel functioning pathways. Two major streams of information flow within the cor­tical visual sensory systems ( Fig. 1). The small-fiber, slower- conducting parvocellular, or P, sys­tem originates in small retinal ganglion cells and travels via small axons to synapse in the parvocel­lular layers of the lateral geniculate nucleus ( LGN). Fibers then course through the optic radiations to synapse in the 4c( 3 layer of area VI. Fibers then pass ventromedially to the inferior temporal cortex ( area V4). This pathway is important for process­ing information related to fine spatial resolution, color, size discrimination and fine stereopsis, and, hence, object recognition. Lesions of this pathway to V4 cause prosopagnosia and cerebral achro­matopsia. The large- fiber, faster- conducting magnocellu-lar, or M, system synapses in the magnocellular layers of the LGN. Fibers then pass through the Manuscript received October 25, 1995. From the Department of Neurology, College of Medicine, The University of Iowa, Iowa City, IA, U. S. A. Address correspondence to Dr. Michael Wall, Department of Neurology, College of Medicine, The University of Iowa, Iowa City, IA 52242, U. S. A. optic radiations to synapse in the 4ca layer of the occipital cortex ( VI). Fibers then course through cortical area V3 and flow dorsolaterally in the tem­poral lobe to area MT ( V5). This pathway is impor­tant for perception of motion and flicker at high temporal frequencies. Lesions of this pathway are associated with Balint's syndrome. Celesia and colleagues ( 1) reviewed the anat­omy, physiology, and functional properties of the M- and P- cell pathways of the visual system. Ret­inal ganglion cell physiology and the anatomy and physiology of the cortical areas important for vi­sual processing are discussed. Clinical syndromes as a result of damage to specific visual cortical ar­eas are also reviewed. In an important article, Nealey and Maunsell ( 2) studied the magnocellular and parvocellular con­tributions to the responses of neurons in macaque striate cortex. They tested the hypothesis that the ventral stream of visual processing receives pre­dominantly parvocellular signals ( Fig. 1). To do this, they recorded visual responses from the su­perficial layers of VI, which creates the temporal stream, while selectively inactivating either the magnocellular or parvocellular subdivisions of the LGN. Inactivation of the parvocellular subdivision reduced neuronal responses in the superficial lay­ers of VI, but the effects of magnocellular blockade were generally as pronounced or stronger. Inter­estingly, individual neurons were found to receive contributions from both pathways. Their results failed to support the idea that cytochrome oxidase blobs or interblobs in VI convey magnocellular contributions of visual processing. Instead, they found that magnocellular signals made major con­tributions to responses throughout the superficial cortical layers. These results argue against a direct 23 24 M. WALL V4 •*" higher visual areas 1 monocellular T *" \ Ufh contrast itnsiuvity lov rtiotution Visual Area 2 li^ gigfgiawsww^ Bgii « Primary Visual Cort* c FIG. 1. Functional segregation in the primate visual system ( from Livingstone). Over­lap in the functions of these systems is a theme found in the 1994 literature ( 52). mapping of the subcortical magnocellular and par-vocellular pathways onto the dorsal and ventral cortical visual processing streams. It appears that the simple notion of dorsal and ventral visual pro­cessing streams, although useful, is an oversimpli­fication of the visual information flow. COLOR PERCEPTION Vaina ( 3) also reviewed the functional segrega­tion of color and motion processing in human vi­sual cortex. She described two stroke patients, each with a lesion in a different cortical visual pro­cessing stream ( M or dorsal pathway and P or ven­tral pathway), each of whom underwent extensive psychophysical studies. Magnetic resonance imag­ing ( MRI) showed bilateral lesions; in one patient, the lesion involved the ventromedial portions of the occipital and temporal lobes and in the other, the lesion involved the dorsal posterior cerebral hemisphere. The first patient had achromatopsia of central origin, prosopagnosia, visual agnosia, and alexia without agraphia. His depth and mo­tion perception, including recognition of moving objects, was normal, along with a bilateral superior visual field defect, which, curiously, did not re­spect the vertical midline. In contrast, the patient with the dorsolateral lesion had deficits of stereop-sis, spatial localization, and motion perception. Recognition of objects, and color and form discrim­ination were normal. Vaina reviewed the ongoing debate regarding the extent to which these path­ways are segregated. Paulson and coworkers ( 4) studied two patients with unilateral ventromedial occipitotemporal in­farcts that produced inferior quadrantic homony­mous achromatopsia and an accompanying supe­rior homonymous quadrantanopia; this superior homonymous quandrantanopia is typical for cases of hemiachromatopsia. Since achromatic vision was preserved in the accompanying inferior quad­rant, the authors concluded the defect of color pro­cessing could not be due to a lesion of primary visual cortex. MRI and single- photon emission-computed tomographic ( SPECT) studies of both patients showed lesions in the lingual and fusi­form gyri. Although the homonymous quadrantic defect in color processing was profound, interest­ingly, neither patient was aware of it. Heywood and coworkers ( 5) described a patient who saw the world in shades of gray ( total cerebral achromatopsia). He performed no better than chance on Farnsworth Munsell 100 Hue testing and was unable to distinguish between any two colors when they were matched for brightness. However, he performed normally when asked to detect a single colored square concealed in a gray checkerboard if the color was maximally saturated J Neuro- Ophthalmol, Vol. 16, No. 1, 1996 ANNUAL REVIEW- VISUAL SYSTEM AND CORTICAL FUNCTION 25 and the range of luminance contrasts was small. In other words, saturated chromatic and achromatic boundaries were easily perceived as different when they were of similar luminance contrast ( isolumi-nant), even if the boundaries were blurred. Inter­estingly, increasing the luminance contrast of the achromatic border made the chromatic- achromatic borders perceptually similar. The authors con­cluded that the patient's contrast vision was medi­ated by a mechanism that extracts color or lumi­nance contrast without distinguishing between them; he could, therefore, use wavelength to ex­tract form. Buchner et al. ( 6) studied the timing of arrival of signals in area V4, the purported cerebral color area in humans. They used visual evoked poten­tials ( VEPs) to color and gray " Mondrian" stimuli ( stimuli that look like the modern artist Mondri­an's paintings, which comprise various series of horizontal and vertical lines with the squares and rectangles filled with black, white, and primary colors). They identified three active brain regions that corresponded to areas VI, V2, and V4. There was sequential, but overlapping, activity in time, with no difference in magnitude between VEPs to color and gray stimuli. The authors concluded that their analysis of the difference of the color poten­tials minus the gray potentials isolated activity re­sulting from color stimulation to the presumed lo­cation of area V4. Davidoff and colleagues ( 7) described a patient with color anomia due to stroke involving the left infracalcarine cortex. Besides the marked color anomia, the patient had a deficit naming pictures with normal reading ability. Objects were named accurately with either visual inspection or with tac­tile inspection. The authors argue that the patient's " picture naming deficit" was dependent on a dis­order of recognition involving access to the stored structural descriptions for objects. They hypothe­sized a similar functional deficit to account for the impaired color naming. The site of the cortical damage-- left inferior calcarine cortex- suggested to them that recognition disorders can result from a unilateral left- sided lesion. PROSOPAGNOSIA ( FACE AGNOSIA) De Renzi and coworkers ( 8) reported three prosopagnosic patients in whom MRI and com­puted tomography ( CT) scans documented a le­sion of the right occipito- temporal areas. Positron emission tomography ( PET) confirmed that hypo-metabolism involved the right hemisphere only. Their review of 27 cases with neuroimaging evi­dence and four surgical cases again confirms the fact that prosopagnosia can be associated with right hemisphere damage alone. They agree that the inability to recognize familiar faces is rare and not present in many patients with only right tem-poro- occipital damage. They suggest that some right- handers do not have such clear- cut right hemispheric specialization for processing faces. They believe that in only a minority of right hand-ers is the specialization so marked that following damage to the right hemisphere, the healthy left hemisphere cannot compensate. Diamond and associates ( 9) studied a prosopag­nosic patient with multiple traumatic hematomas including one in the right occipital area. Although the patient was densely prosopagnosic, she per­formed normally in word and object recognition tasks, and had no trouble recognizing names of celebrities. Surprisingly, she performed at the same level as controls when she was required to make a forced- choice response for the correct name of a famous face, even though the famous face evoked no feeling of familiarity for her. She performed at chance levels in a forced- choice face familiarity decision task, but showed evidence of covert recognition in a face- name learning task where familiar faces were paired with names. Al­though prosopagnosic patients are unable to at­tach names to faces, they process other features visually linking the person to the face. Allison and colleagues ( 10,11) studied face rec­ognition in human extrastriate cortex in 24 patients by recording from electrodes chronically im­planted on the surface of the occipito- temporal cor­tex. They recorded while subjects viewed tradi­tional faces, equiluminant scrambled faces, cars, scrambled cars, and butterflies. A surface- negative potential from the extrastriate cortex, N200, was evoked by faces but not by the other categories of stimuli. They found the N200 only in small regions of the left and right fusiform and inferior temporal gyri. Electrical stimulation of the same region fre­quently produced a temporary inability to name familiar faces. The results show that distinct re­gions of inferior extrastriate visual cortex are spe­cialized for the recognition of faces. Tovee and coworkers ( 12) recorded responses of single neurons in the inferior temporal cortex and anterior part of the superior temporal sulcus of three awake macaque monkeys during a visual fix­ation task that included viewing faces. Stimulus images were presented either in the center of the display area or at eccentric positions. They re­corded from face- selective cells, and compared re­sponses for fixation at each position for both effec- / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 26 M. WALL tive and noneffective face stimuli for each cell. The firing rates of most neurons to an image did not change while visual fixation was as far eccentric as the edge of the face. Also, they showed only a small reduction when the fixation point was up to 4° from the edge of the face. Stimulus selectivity across faces was maintained throughout this re­gion of the visual field. They reported that nearly six times more information was carried during these neurons' firing rate about the identity of an image than about its position in the visual field. These findings show that in temporal cortical vi­sual areas, there are visual cells that respond to the identity of an image independently of its retinal position. Rentschler et al. ( 13) studied two stroke patients with complementary lesions. One patient had a right inferomedial occipito- temporal lobe lesion and the other a near mirror image left- sided lesion. The authors used these two cases to show similar­ities of local ( receptive field types of filtering) and global ( overall) visual processing of the filtered vi­sual stimuli. The patient with the right- sided le­sion had prosopagnosia; the one with a left- sided lesion had pure alexia with color anomia. The pa­tient with the right posterior stroke could read text but could not identify whose handwriting it was; conversely, the patient with the left posterior stroke could not read text but knew who had writ­ten it. In other words, the patients showed com­plementary dissociation of the analysis of hand­written text. Analysis of spatial vision showed that the prosopagnosic patient had no problem seeing texture elements, attributed to local processing, when presented in isolation. However, she per­formed poorly with Moire and texture perception ( global processing). In other words, she suffered from a selective loss of global visual perception. Again, conversely, the alexic patient performed well with Moire patterns but did poorly with ( com­plex) texture elements and textures. She could pro­cess patterns composed of simple elements of fig­ures, but failed with stimuli that required integra­tion of features. This finding of a concomitant dissociation of local and global visual processes in the two patients supports the view that prosopag­nosia as well as alexia are the most prominent as­pects of more general deficits of visual perception. VISUAL AGNOSIA Teuber defined visual agnosia as " a normal per­cept stripped of its meanings." Damasio opera­tionally defines visual agnosia as " a disorder of higher behavior confined to the visual realm, in which an alert, attentive, intelligent, and non-aphasic patient with normal visual perception gives evidence of not knowing the meaning of those stimuli- that is of not recognizing them ( 14)." Visual agnosia is divided into " true" ( asso­ciative) agnosia and apperceptive agnosia. Asso­ciative agnosics correctly integrate the structural components of an object but cannot associate this structure with meaning. However, apperceptive agnosics are unable to perceive the integrated structure of an object. This deficit is reflected in their inability to copy a drawing and match visual stimuli or generate an image of a whole entity given a part of it. Feinberg and coworkers ( 15) reviewed the neu-roanatomical substrate of associative visual agno­sia. They examined three patients whose associa­tive visual agnosia encompassed objects and printed words, sparing faces. CT scans revealed unilateral dominant occipitotemporal stroke. Study of these and scans of four previously re­ported cases with associative agnosia showed the dominant parahippocampal, fusiform, and lingual gyri were the most extensively damaged cortical regions and were involved in all cases. The only white matter tract damaged was in the temporal lobe- the inferior longitudinal fasciculus was se­verely involved in all. They concluded there was a form of associative visual agnosia with agnosia for objects and printed words sparing face recognition due to unilateral damage. These authors believe damage or disconnection of dominant parahippo­campal, fusiform, and lingual gyri to be the neces­sary lesion for associative visual agnosia. Shelton and colleagues ( 16) reported an individ­ual with a bilateral infarction of his inferior tempo­ral and occipital association cortices sparing striate cortex. He had impaired visual recognition of ob­jects, faces, colors, words, and gestures with nor­mal standard visual function testing. The patient showed a failure to relate and integrate individual elements to the whole. These results suggest that while internal representations were intact, the pa­tient was unable to form adequate perceptual rep­resentations. The complexity of the visual agnosias is underscored by the conclusion reached by these authors- the patient's loss of gesture recognition was due to an associative agnosia and his inability to recognize objects to an apperceptive agnosia. MOTION PERCEPTION There is now compelling evidence that motion information is carried predominantly by the large- / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 ANNUAL REVIEW- VISUAL SYSTEM AND CORTICAL FUNCTION 27 fiber, faster conducting M system ( see Fig. 1). Many studies have shown that cortical area V5, also know as area MT, is a central station for pro­cessing motion stimuli in the monkey. Using a PET activation technique, Dupont and coworkers ( 17) showed that many areas in the human brain are involved with visual motion perception ( this is complementary to data of Nealy and Maunsell dis­cussed above). Besides bilateral foci at the border between Brodmann areas 19 and 37, a V1/ V2 focus and a focus in the cuneus, they observed activa­tions in other visual areas, the cerebellum, and cor­tical vestibular areas. In addition, Nawrot and Rizzo ( 18) found deficits in motion perception in patients with midline cerebellar lesions. Celebrini and Newsome ( 19) studied neuronal and psychophysical sensitivity to motion signals in extrastriate area MST of the macaque monkey, an area close to area MT that also is specialized for motion perception. They recorded responses of single neurons in area MST while the monkeys classified the direction of motion in a set of random dot cinematograms. This is the classic stimulus for motion perception experiments. With these stim­uli, there are two sets of intermixed moving dots- one set of " noise dots" moves in a random direc­tion and another set of " signal dots" in a specified direction; by varying the percentage of " signal dots" a threshold can be measured. Using random dot motion, the authors simultaneously measured the monkeys' psychophysical thresholds for direc­tion discrimination and the responses of single neurons. They found that neurons in cortical area MST were exquisitely sensitive to motion signals in the display. They reported thresholds for discrim­inating motion direction that were equal to the monkey's psychophysical thresholds! In both re­spects, MST neurons were indistinguishable from neurons in neighboring area MT, a major source of afferent input to MST. They also found area MST neurons carry signals appropriate for supporting psychophysical performance on random dot cine­matograms over a wide range of stimulus config­urations. This important article not only further defines the functions of MT and MST but also fur­ther validates these stimuli as psychophysical probes. In a related study, Zohary and colleagues ( 20) of the same laboratory investigated the neuronal plasticity associated with learning to respond to the random dot cinematogram stimuli. They re­corded the responses of directionally selective neu­rons in visual cortex, while rhesus monkeys prac­ticed a familiar task involving discrimination of motion direction. Each animal experienced a short-term improvement in perceptual sensitivity during daily experiments of several hundred trials. This short- term improvement in neuronal sensitivity that accompanied the increase in perceptual sensi­tivity mirrored the perceptual effect both in mag­nitude and time course. This finding suggests that improved psychophysical performance could re­sult directly from increased neuronal sensitivity within a sensory pathway. These results are appli­cable to the learning effect present in clinical con­ventional automated perimetry. Patzwahl and colleagues ( 21) also used simple random dot motion stimuli along with more com­plex motion stimuli to study motion elicited VEPs. Three classes of motion stimuli were used: random dot motion, drift- balanced motion ( a flickering bar in front of a static background), and theta, or par­adoxical, motion ( an area of dots is shifted oppo­site to the direction of the dot motion). These three classes require mechanisms of increasing complex­ity to be processed. Large- field motion and coun-terphase flicker were used as control stimuli. The authors found the responses evoked by the three classes of object motion did not differ. Use of this type of VEP in the clinical situation has promise for evaluating extrastriate visual motion perception. Motion Perception in Alzheimer's Disease Gilmore and coworkers ( 22) studied the motion sensitivity of 15 Alzheimer's disease patients and 15 healthy, elderly adults using random dot mo­tion stimuli. The Alzheimer's disease patients ex­hibited higher thresholds for detecting the direc­tion of motion. Contrast sensitivity testing results paralleled the motion threshold elevations ( but the correlation was not very strong) in the Alzheimer's disease group suggesting loss before the human homologues to areas MT ( V5) and MST. There also was a significant relationship between dementia severity, Mini- Mental State Exam, and motion sen­sitivity. The authors stated that the results support the hypothesis that Alzheimer's disease results in dysfunction of primary visual cortex, but the re­sults are equally well explained by optic nerve damage. Silverman and colleagues ( 23) investigated mo­tion perception in Alzheimer's disease by compar­ing the conscious acknowledgment of motion per­ception with the reflex recognition motion as dem­onstrated by recording eye movements to an optokinetic stimulus. Motion perception thresh­olds were significantly elevated in Alzheimer's dis­ease patients compared with controls, but motion detection thresholds with the optokinetic nystag­mus ( OKN) paradigm were normal. This dissocia- / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 28 M. WALL tion of perception and detection of motion in early Alzheimer's disease patients parallels histologic evidence of a disconnection between primary and association visual cortices. Another explanation is that it simply took a stronger stimulus to capture enough of the Alzheimer's patients' attention for them to respond. BALINT'S SYNDROME Balint's syndrome is a triad of symptoms, in­cluding ( a) inability to perceive and describe the composition of a scene ( simultanagnosia), ( b) er­rors in visually guided pointing ( optic ataxia), and ( c) spasm of fixation ( psychic paralysis of gaze). For an excellent review, the reader is directed to Rizzo ( 24). Optic ataxia or errors in visually guided pointing behavior was studied by Fabre- Thorpe and col­leagues ( 25). They ablated visual cortical areas VI, V2 and V3 and the lateral suprasylvian visual areas in cats. They found preservation of pointing accu­racy toward moving targets after the ablations but permanent impairment of this behavior toward non- moving targets. However, there was an in­crease in latency of the response to the moving target. Wakai et al. ( 26) used PET to study a patient with posterior cortical atrophy also called the vi­sual variant of Alzheimer's disease. A 65- year- old man had a 5- year history of slowly progressive ap­perceptive visual agnosia and Balint's syndrome, with preserved intelligence and language abilities. A PET study revealed that cerebral metabolism was reduced in the dorsal regions of the cerebral cortex and was asymmetric with the main site of damage on the right. The degree of asymmetry increased dorsally supporting the proposed in­volvement of the dorsal stream of visual informa­tion processing in this disorder. Victoroff and coworkers ( 27) also studied pa­tients with posterior cortical atrophy. Their aim was to determine whether posterior cortical atro­phy was associated with distinct, uniform neuro-pathologic findings. Three individuals with pro­gressive dementia that began with higher visual dysfunction were autopsied. They found three separate neuropathologic patterns: subcortical gli­osis, a " classic" Alzheimer's disease pattern, and Creutzfeldt- Jakob disease. They concluded that posterior cortical atrophy is a clinically homoge­neous but pathologically heterogeneous syn­drome. Posterior cortical atrophy should be thought of as a neuropathologic entity of which the visual variant of Alzheimer's disease is one cause. PURE ALEXIA ( ALEXIA WITHOUT AGRAPHIA) Arguin and Bub ( 28) in a rehabilitation attempt, studied a patient with the letter- by- letter type of reading commonly found with pure alexia. With the training procedures, the patient responded to matched pairs of letters ( as same or different) and time pressure was enforced in naming of the letter strings. Although this training procedure failed to produce any change in the operations used by the patient to encode isolated letters or words, there was a significant increase in the overall reading speed. The authors attribute these results to an increased rate of letter identification and faster in­tegration of individual letters into letter combina­tions. They propose that the letter- by- letter read­ing procedure may follow from an incapacity to encode visual letters as abstract types. Coslett and Monsul ( 29) used transcranial mag­netic stimulation to test the hypothesis that the right hemisphere mediates the remaining reading capabilities of patients with pure alexia. A patient with partially recovered pure alexia was asked to read aloud briefly presented words, half of which were shown in association with transcranial mag­netic stimulation of the right or left hemisphere. The authors found that transcranial magnetic stim­ulation of the right, but not the left, hemisphere disrupted oral reading in pure alexics, supporting the author's notion that the remaining reading abilities of patients with pure alexia reside in the right hemisphere. ASTEREOPSIS In another study using transcranial magnetic stimulation, Takayama and Sugishita ( 30) studied loss of stereopsis induced by magnetic stimulation of occipital cortex. Three healthy subjects under­went repetitive transcranial magnetic stimulation with a coil held tangentially against the skull sur­face 3 or 4 cm above the inion, while viewing a random- dot stereogram through red- green glasses. They positioned the coil over the midline of the superior occipital lobes. All three subjects experienced loss of stereoscopic perception during stimulation. A stimulus duration of > 0.2 s and a stimulus frequency of > 10 Hz was optimal in dis­rupting stereopsis. The authors concluded the bi­lateral superior occipital cortices are involved in stereopsis. / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 ANNUAL REVIEW- VISUAL SYSTEM AND CORTICAL FUNCTION 29 VISUAL HALLUCINATIONS Shedlack and colleagues ( 31) studied the associ­ation of geniculocalcarine hyperintensities on brain MRI to visual hallucinations in the elderly. They compared MR scans of five geriatric patients presented with formed visual hallucinations with those of 12 healthy, elderly subjects for the pres­ence and extent of subcortical and periventricular signal hyperintensity. While the number of dis­crete brain lesions did not differ between groups, scans from the patient group contained a higher incidence and greater mean size of periventricular signal hyperintensity posteriorly. Peripheral field loss was present in all the patients. The authors concluded that the presence of these larger signal abnormalities suggest that structural abnormalities in the primary visual pathway predispose some older individuals to visual hallucinations. MICROPSIA Cohen and coworkers ( 32) studied two cases of hemimicropsia, a rare visual disorder character­ized by an apparent reduction of the size of objects when presented in one hemifield. The first patient, an art teacher could accurately describe his abnor­mal visual perception. The authors studied the sec­ond patient with a size comparison task ( which showed his deficit). Since the size of a given object is normally perceived as constant across any posi­tion, hemimicropsia can be thought of as a limited violation of the size constancy principle. Postmor­tem and MRI analysis of patients, one with a left-sided and one with a right- sided lesion showed pathology in areas 18 and 19 with involvement of the underlying white matter to be common to both. The lesions appear to be in the posterior wa­tershed zone. NEURONAL PLASTICITY IN VISUAL CORTEX Loss of sensory input to adult neocortex can lead to a reorganization of cortical topography within the deprived area over months. Darian- Smith and Gilbert ( 33) reported axonal sprouting accompa­nies this functional reorganization in adult cat stri­ate cortex. They showed that weeks after binocular retinal lesions silenced corresponding areas in the striate cortex in the adult cat, this cortex again be­comes responsive to visual stimulation placed ad­jacent to the blind area. They attributed this find­ing to axonal sprouting of long- range laterally pro­jecting neurons. Kapadia and coworkers ( 34) studied short- term cortical neuronal plasticity in human vision. They used subjects' ability to localize in space next to an artificial scotoma while they showed a dynamic pattern over a surrounding region. They found that the ability to localize the position of line seg­ments was strongly biased toward the interior of the scotoma. They attributed this " shift" or misas-signment of position to receptive field expansions within the artificial scotoma. They concluded this shift begins within 1 s of stimulus presentation, suggesting that receptive fields are constantly al­tered by their local context and that these dynam­ics are a part of normal vision. Leuba and Kraftsik ( 35) studied pathologic spec­imens from visual areas 17 and 18 in 13 Alzhei­mer's disease patients and 11 controls. In Alzhei­mer's disease cases, the mean neuronal density was significantly decreased by 30% in areas 17 and 18, while the glial density was increased signifi­cantly only in area 17. In Alzheimer's disease, the number of senile plaques was similar in areas 17 and 18, while that of neurofibrillary tangles was higher in area 18. The discrepancy between the loss of neurons and the amount of neurofibrillary tangles suggests that neuronal loss can occur with­out passing through neurofibrillary tangle degen­eration. PRIMARY VISUAL CORTEX Good and coworkers ( 36) reviewed cortical vi­sual impairment in children. The authors provide a review of the epidemiology, anatomy, clinical and laboratory diagnosis, methods and etiologies of cor­tical visual loss in children. Peri- or postnatal hyp-oxia- ischemia was the most common cause of cor­tical visual loss in children. It also occurs following trauma, epilepsy, infections, drugs or poisons, and specific neurologic diseases. They suggest that due to the uncertainty concerning the prognosis in cortical visual impairment, clinicians should re­main optimistic about the child's potential for some vision recovery. The authors point out the many differences in causation of childhood and adult cortical visual impairment. McFadzean and colleagues ( 37) studied the rep­resentation of the visual field in occipital striate cortex. They correlated the perimetric and imaging findings in a larger series of patients with striate cortical disease; their results are in agreement with Horton and Hoyt's ( 38) proposed map of the rep­resentation of the visual field in the striate cortex with the central 10° occupying at least 50% of stri­ate cortex. / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 30 M. WALL CORTICAL BLINDNESS " Blindsight" is the ability of some blind patients to describe attributes of visual stimuli they have no conscious awareness of seeing. It has been pro­posed that this visual perception is mediated by the retino- tectal visual system; others believe " blindsight" is merely due to residual function of tiny islands of vision within the geniculocalcarine visual pathway. This debate on the existence of " blindsight" continues. A new standard for evaluation of patients with " blindsight" comes from Fendrich's study ( 39). A Purkinjie image eye tracker was connected to an image stabilizer to ensure accurate and stable ret­inal projection of stimuli. Then using a two-alternative forced choice testing strategy, perimetry was performed on their patient who had a macular sparing left homonymous hemianopia. This test­ing revealed, hidden in the patient's hemianopia, an isolated one degree island of residual vision that was not found by conventional automated pe­rimetry. Stimuli presented to this island could be detected and discriminated, although the subject reported he did not see them. The existence of this island of vision implies a corresponding island of functioning cortex within the patient's lesion. This report from 1992 calls into question all other re­ports of " blindsight" and sets a rigorous standard that should be met before concluding vision is " ex-trastriate." Brent and colleagues ( 40) reported a pa­tient similar to Fendrich's with residual vision that is able to identify colors by a forced choice proce­dure although he denied any conscious perception of color. Kerkhoff and coworkers ( 41) trained 22 patients with homonymous hemianopia due to stroke with saccadic eye movement strategies to improve their visual performance. Their subjects practiced using anchor points, finger position cues and scanning strategies that covered the hemianopic area. They reported an increase in visual search field size with transfer of treatment gains to functional measures. These improvements were stable at a 3- month fol­low- up visit. The authors suggested that there was " recovery" of scotomatous regions of the visual field but the results are more easily explained by simply learning to use an efficient strategy for scanning the visual field. Drubach and associates ( 43) used brain SPECT to study a case of cortical blindness. Their patient had a unilateral lesion with CT and MRI scanning but bilateral abnormalities on SPECT scanning. The SPECT images correlated best with the patient's clinical status of cortical blindness. / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 VISUAL ASSOCIATION CORTEX We continue to learn more about cortical area V4. Thought by Zeki to be a center for color per­ception ( 44), it has broader function. It appears important for selecting targets of less contrast, smaller size or slower rates of motion from an ar­ray of similar stimuli ( 45). In addition, pattern per­ception ( 46) and attention modulation have been proposed ( 47). A two- part study by Motter ( 48,49) advances our knowledge of this critical way- station of visual in­formation processing. Rhesus monkeys trained to perform various discrimination tasks were used for single neuron recordings in area V4. He found that the attentive selection for various stimulus features is associated with neural activity in area V4, sup­porting the view V4 is important for much more than color processing. In a companion experiment, Motter again trained Rhesus monkeys on a conditional discrim­ination task, this time to assess whether attentive selection for a color or luminance stimulus feature would affect visual processing in extrastriate area V4. Again, the neural activity in area V4 was asso­ciated with potential targets in the visual scene at the expense of background objects. These obser­vations offer a physiological counterpart to psy­chophysical studies suggesting that stimuli can be preferentially selected in parallel across the visual field based on a unique color or luminance feature. These experiments emphasize cortical area V4 is important for the distributed processing of stimuli by controlling attention to discriminate unique fea­tures of a stimulus imbedded within other similar stimuli. This selection process is probably used for many stimuli besides color including pattern, lu­minance, rate of movement and size. Givre and coworkers ( 50) continued their pur­suit of the source of the VEP. They report their experience studying the contribution of extrastri­ate area V4 to the surface- recorded flash VEP in the awake macaque. Data were obtained using multi-contact electrodes from cortical areas VI and V4 in three awake macaques. As expected, they found the major area VI contribution was to early wave components and major contributions to the later components arise from V4. However, early affer­ent- triggered inhibition in V4 also produced a small contribution to the early wave component. They unexpectedly found increased response la­tencies in V4 ( compared with those from VI) sug­gesting an input to V4 that bypassed VI! This sug­gests a parallel processing component of visual system organization. In other words, V4 was acti- ANNUAL REVIEW- VISUAL SYSTEM AND CORTICAL FUNCTION 31 vated earlier than expected suggesting information was bypassing the superficial layers of VI. Studies like this one not only advance our understanding of the VEP but also provide hope for new and more clinically relevant uses for the VEP. Visual area V2 of macaque monkey cerebral cor­tex is the largest of the extrastriate visual areas, but little is known of its neuronal properties. Regions in VI and V2 defined by cytochrome oxidase stain­ing have distinct characteristics that allow these regions to be classified as belonging to one of the two prominent cortical visual streams of informa­tion processing. Superficial layers of VI contain tissue rich in cytochrome oxidase that are known as blobs or puffs. There are also regions of thick and thin stripes of cytochrome oxidase- rich tissue. Levitt and coworkers ( 51) studied the receptive fields and functional architecture of macaque V2 regarding parvocellular, P, or magnocellular, M, inputs. They recorded the activity of single units representing the central 5° of the visual field in all laminae of V2 in anesthetized macaque monkeys. Geometric targets and drifting sinusoidal gratings that varied in orientation, spatial frequency, drift rate, contrast, and color were used as stimuli. They found that the physiological organization of V2 was much more homogeneous than previously ap­preciated. As with other studies published in 1994, data showing much overlap between the dorsal and ventral processing streams were presented. Acknowledgment: The author thanks Drs. 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