Disorders of Higher Cortical Visual Function

James Goodwin, MD

AddressUniversity of Illinois Eye & Ear Infirmary, 1855 West Taylor Street, Chicago, IL 60612, USA. E-mail: jamegood@uic.edu

Current Neurology and Neuroscience Reports 2002, 2:418–422Current Science Inc. ISSN 1528–4042Copyright © 2002 by Current Science Inc.

IntroductionReaders are referred to an extensive review of this litera-ture that was published in 2001 [1••]. This current reviewconcentrates on clinically relevant additions to the bur-geoning literature on disorders of higher cortical visualfunction that have appeared during the past year. Specificdisorders of higher cortical visual dysfunction were cho-sen for review based on the existence of clinically relevantand interesting published work on the disorder in thepast year.

BlindsightObservations of residual elementary visual function afterlesions of the retrogeniculate visual pathways or striate cor-tex were initially considered to represent incomplete dam-age to the visual pathways or cortex [2]. Early observationsof monkeys after striate cortex removal documented thepersistence of some elemental visual function [3]. Laterwork has confirmed the presence of various manifestationsof residual vision, such as visually guided behavior aftercomplete destruction of primary visual cortex [4]. Weis-krantz et al. [5] called this "blindsight," a term that hasbecome the standard in referring to this phenomenon. Anextensive literature has accumulated in this area despite the

persistence of critics who contend that it is simply reflec-tive of incomplete destruction of the striate cortex.

Spatial and temporal characteristics of blindsightThe spatial and temporal tuning characteristics of blind-sight were previously documented for a patient, G.Y. [6],and more recently for a second patient, C.S., using thesame test methods [7]. Both patients had long-standingdense hemianopsia with less than 3° of central sparing.Results in the two patients were compared to see if blind-sight characteristics reported in the literature couldbe generalized.

Sine wave or square wave gratings were presented in theblind hemi-field. During each stimulus run, the subjectviewed the fixation target during two time intervals, and astimulus was presented in one of the two intervals. Thegratings were presented at various contrasts and with either10-Hz flicker or static presentation. For each stimulus runthe patient had to indicate, by pressing one of two buttons,which of the two intervals contained the stimulus; a choicehad to be made for each interval pair. In addition, for eachblock of two intervals, the subject had to press another but-ton to indicate if he or she had had any conscious aware-ness of a visual stimulus in either of the intervals.Performance is classified as type I if there was no consciousawareness of any visual stimulus and type II if there wassome awareness of a stimulus [8]. Type I performance isclassified as "guessing." Patient C.S. detected gratings sig-nificantly better than chance at spatial frequencies lessthan 3 cycles/degree and at contrasts above 20%, withincreasing detection as contrast increased up to 100%.Detection was consistently better for type II than for type Itrials, and performance was quite similar to that of patientG.Y. Detection was high for both stationary gratings andfor gratings that were flickered at 10 Hz, but awareness ofthe stimulus was much less for stationary gratings than forflickered gratings. Awareness was even less if the stationarygratings had a gradual onset and offset as compared withabrupt appearance and disappearance.

In a motion-discrimination task, a circular dot stimuluswas moved either toward or away from the midline in thehemi-anopic field. Patient C.S. had to choose which direc-tion the dot moved and whether or not she was aware ofany visual stimulus during each trial. Detection (of whichdirection was presented) was significantly above chance fora wide range of stimulus speeds and improved with faster

In the past few years, there have been significant advances in the understanding of how the so-called higher cortical functions are organized and mapped into various anatomic brain regions. There has been considerable refinement in lesion localization provided by magnetic resonance imaging (MRI), so the precise regions that are damaged in patients with particular types of visual perceptual problems can be demonstrated. In addition, functional MRI has provided insight into neural networks serving higher cortical func-tions in normal human subjects as they perform perceptual and cognitive tasks.

Disorders of Higher Cortical Visual Function • Goodwin 419

speeds. C.S. and G.Y.'s performances were not significantlydifferent. The authors conclude that blindsight lacks sensi-tivity to high-spatial frequencies (is low resolution), andlow-contrast and the temporal tuning characteristics showno dominance of either parvocellular- or magnocellular-mediated responses.

Color blindsightIt is generally accepted that color discrimination and per-ception at the cortical level is mediated in the inferioroccipital lobe in the region of the posterior fusiform andlingual gyri [9]. Although there has been controversy overthe exact extent and location of cortex specialized for colordiscrimination in humans and other primates, the pres-ence of residual color discrimination after extensive corti-cal lesions or ablations suggests that a form of blindsightexists for color perception [10].

Cowey et al. [11] performed radioactive labeling of reti-nal ganglion cell axons in the dorsal and ventral optictracts in normal macaques and in animals after long-stand-ing removal of striate cortex on one side. After a radioactivetracer was implanted in the optic tract, ganglion cells in theretina were labeled retrogradely and cells of the pregenicu-late and lateral geniculate nuclei were labeled antero-gradely. Labeled ganglion cells were classified by soma sizeand dendritic morphology. Tracer implants in the dorsaloptic tract resulted in retrograde labeling of mostly parvo-cellular β ganglion cells (color opponent cells) in the ret-ina and anterograde labeling of parvocellular lateralgeniculate, as well as pregeniculate nuclei. The fact that sig-nificant numbers of retinal parvocellular β ganglion cellsproject to the pregeniculate nucleus was taken as evidencethat these could contribute to residual wavelength process-ing after total atrophy of the striate cortex and lateral genic-ulate nucleus.

Just to illustrate the fact that skeptics still abound inthis subject area, we can cite the work of Faubert and Dia-conu [12], who developed an intraocular reflection andabsorption model that accounts for luminance and colordetection in hemi-anopic areas of visual field of hemi-decorticate patients. The authors observe that future blind-sight experiments having to do with brightness or colordetection and discrimination have to allow for scatter oflight from the stimulus onto seeing portions of the retina,even when the stimulus is delivered as a highly focusedimage to the blind hemi-field. There are many recentblindsight studies in which detection of patterns in blindhemi-fields has been demonstrated with rigorous controlof average luminance during pattern presentation and inthe interstimulus (blank) intervals [6], so the light-scattercriticism pertains mostly to older studies.

Processing emotional content in blindsight imagesOf course, discriminations that do not depend on changesin luminance or stimulus wavelength can hardly beexplained by intraocular scatter of light, and there have

been many such examples over the years. A notable indi-vidual subject, G.Y., has been studied repeatedly for a num-ber of years and has demonstrated the abil i ty todiscriminate different emotional expressions in faces pre-sented to his blind hemi-field [13]. A central postulate inblindsight research has been that it is mediated by anextrastriate pathway involving the superior colliculus andposterior (visual) thalamus (pulvinar) [5]. Viewing angryfaces has been shown to cause activation of the amygdalain the subject G.Y. [13], as well as in normal persons pre-sented masked, "unseen" angry faces in a tachistoscopicdisplay [14]. Both studies used positron emission tomog-raphy (PET) scanning to survey the activated brain areas.The visual masking in normal subjects involves brief (<40ms) presentation of the emotional face image followedimmediately by a masking stimulus—a second face withneutral emotion. The initial stimulus was never con-sciously perceived by the subjects when followed by themask, but if the initial stimulus was an angry face it alwayscaused changes in skin conductance, indicating an auto-nomic response to the unseen angry face.

The study of subject G.Y. was recently extended usingfunctional magnetic resonance imaging (fMRI) blood oxy-gen level-dependent (BOLD) imaging to demonstrate theneuroanatomic structures that were differentially activatedas G.Y. responded to fearful, angry, or neutral faces pre-sented in his blind hemi-field. Throughout the experiment,G.Y. denied having seen or perceived any faces. Presenta-tion of fearful or fear-conditioned faces in his blind hemi-field elicited differential responses in the amygdala bilater-ally along with differential activation of the superior colli-culi and posterior dorsal pulvinar. Increased condition-dependent colliculo-amygdala and thalamo-amygdalacovariation in subject G.Y. when presented with unseenfearful versus neutral faces supports the presence of a coor-dinated extrastriate visual system for processing emotiveaspects of visual information involving these structures.

Cerebral AchromatopsiaIn primates, the occipital visual area designated as V4has been shown to be specialized for color processing[9,15–18]. It is generally accepted that the lingual gyrusin the inferior occipital lobe is specialized for color pro-cessing and is analogous in humans to the monkey areaV4 [19–21,22••].

One of the remarkable attributes of human color per-ception is "color constancy" [23], in which the apparentcolor of a viewed surface remains the same while the spec-tral makeup of the light falling on that surface is changed.One aspect of this constancy is the ability to discriminatewhether it is the color of the reflective surface or the spec-tral content of the illumination that is changing. This dis-crimination could be based on the ratio between thespectral content of one area as compared with adjacentareas—relational color constancy. When the color of the

420 Neuro-ophthalmology

light changes, these spectral ratios remain invariablebetween differently colored areas, and when the color ofportions of the surface changes, the ratios change from onearea to another [24].

It has been postulated that the cerebral color center "iscritical for the ratio-taking operations that enable the brainto compare the wavelength composition of the lightreflected from one surface and that reflected from sur-rounding surfaces in order to assign a constant color to asurface" [25••].

Bartels and Zeki [25••] used color and achromaticMondrians as visual stimuli in a study of humans with nor-mal color vision using fMRI to show the cerebral centersthat are differentially activated in various viewing situa-tions. Mondrians are aggregates of abstract multicoloredshapes that resemble the artworks of the painter Piet Mon-drian and were used extensively in color investigations byEdwin Land [23]. These figures do not evoke any of thecolor expectations that characterize viewing naturalobjects. In one experiment, subjects' fMRIs were elicitedwhile they viewed colored or achromatic (black, gray/white) Mondrians under illumination that was constantlychanging (either with respect to wavelength compositionor intensity) or under steady, unvarying illumination. Thiscreated numerous combinations of viewing conditionsthat could be compared with one another in repeat fMRIsessions. In this way, the fMRI BOLD activation patternfrom one condition could be subtracted from the patternthat resulted from any other viewing condition, and thecortical areas that were differently activated in the two con-ditions then were the only ones highlighted. The principalfindings of this study are as follows.

In the comparisons between dynamic (color changingillumination) and static illumination of Mondrians, therewas very little activation in primary visual cortex becausethis area was equally activated for the two conditions.There were two distinct, color-activated areas in the fusi-form gyrus—a larger, more posterior area, which theycalled V4 as a corollary to simian cortical visual maps, anda smaller, more anterior area they called V4α. Area V4showed evidence of retinotopic mapping in which upperquadrant stimulation activated medial and anterior sec-tions of the area, and inferior quadrant stimulation acti-vated more lateral and posterior portions. The entirety ofarea V4α was activated with either upper or lower quadrantstimulation and did not show retinotopic organization.

Using naturally or falsely colored fruits and vegeta-bles rather than Mondrians, it was found that viewingnaturally colored objects preferentially activated V4α,along with more anterior areas in the fusiform gyrus thathave been associated with object and face recognition[26], whereas viewing unnaturally colored objects acti-vated V4 and V4α together, but not the more anteriorareas. In each condition (natural or false colors), thefMRI from viewing an achromatic stimulus was sub-tracted from the fMRI generated by viewing the colored

stimulus, and only the color-dependent cortical activa-tion remained in the maps.

Beauchamp et al. [22••] have adapted the Farnsworth-Munsell 100-Hue Test for use in the MRI scanner and haveshown that the activated cortical areas vary with the type ofcolor task that is carried out. Subjects were presented anarray of five color panels in a radial display. The panels atthe 11:00 and 1:00 positions were "anchor" colors, like thefixed caps at the two ends of each 100-Hue Test box. Thesubject had to decide if the three other color panels werearranged in the correct order, counterclockwise from the11:00 panel to the 1:00 panel. He or she pressed the rightmouse button if the panels were in proper sequence andthe left button if they were not. This was compared in alter-nate stimulus runs in which the same discrimination taskwas carried out while viewing an achromatic (variousshades of gray) version of the panels. The array of panelswas centered on the fixation target so both hemi-fieldswere stimulated during presentations that lasted 2.5seconds each.

In Beauchamp et al.'s [22••] study, passive viewing ofchromatic versus achromatic Mondrians activated only asmall portion of the more posterior of the two color-selec-tive sites. It is interesting that in Bartel and Zeki's study[25••], passively viewing Mondrians (no decision orresponse required) under changing illumination—withshifting spectral composition during stimulation—acti-vated both the anterior and posterior zones in the fusiformgyrus, but in the active and passive 100-Hue study, the illu-mination was unvarying during stimulation. One explana-tion might be that the task of performing the 100-Hue test[22••] evokes the same cortical ratio-taking process thatunderlies color constancy as studied by having subjectspassively view color Mondrians under conditions of shift-ing chromatic illumination [25••].

ProsopagnosiaProsopagnosia is a disorder characterized by more or lessisolated inability to recognize faces of persons, even veryfamiliar persons or family members [27]. Prosopagnosiawas first described as an independent form of visual agno-sia in 1947 [28]. The importance of local lesions involvingthe right inferior occipital cortex and inferior longitudinalfasciculus in producing this syndrome has long been pos-tulated [29], but some authors contend that bilateral infe-rior occipital lesions or co-involvement of the splenium ofthe corpus callosum is also required to produce the syn-drome [30]. Cases have been classified as apperceptiveprosopagnosia when the problem involves faulty percep-tual integration of facial features, or associative prosopag-nosia when the defect is matching properly perceived facialfeatures with memories of previously known faces [31].

Another model of prosopagnosia concerns whetherfacial recognition is a holistic function in which all thefacial features are integrated using spatial relationships

Disorders of Higher Cortical Visual Function • Goodwin 421

among the parts. Evidence for this has included the factthat facial recognition is speeded up by prior presentationof facial parts (eg, nose, eyes, mouth, etc.) in a primerimage, and that as the number of facial parts presented inthe primer image increases the rapidity of recognitionexponentially increases—a sign of this holistic integrationacross features. Using the same priming paradigm in a sub-ject with prosopagnosia and object agnosia from previousbilateral temporal lobe damage, it was shown that recogni-tion time improved by prior presentation of facial parts,but the rate of improvement with the addition of morepriming parts was only linear. The authors took this as evi-dence that the holistic synergy of spatial relationshipsamong face parts was defective in this patient [32].

In a patient with developmental or congenitalprosopagnosia, it was found that in addition to having dif-ficulty recognizing faces, the patient had impaired abilityto match different perspectives of amoeba-like forms (vol-umes with smooth curved surfaces) and in recognizing nat-ural but nonface images (animals) [33]. The authorssuggest that prosopagnosia may be part of a more generalproblem dealing with the perceptual handling of curvedand volumetric information.

In most patients, prosopagnosia is accompanied byproblems with object recognition or spatial orientation.Wada and Yamamoto [34] describe a patient with pureprosopagnosia but no defect in object recognition, evenwhen objects were photographically presented in uncon-ventional views. MRI demonstrated a single, right hemi-sphere hematoma limited to the right fusiform gyrus, andlateral occipital region and PET showed normal perfusionin the left hemisphere. The authors point out that all previ-ously reported patients with prosopagnosia have had asso-ciated difficulty recognizing objects, at least whenpresented in unconventional views. Also, this patient wasshown more decisively than previous cases not to have anydysfunction in the left hemisphere, which shows that a sin-gle, right fusiform gyrus and lateral occipital lobe lesion issufficient to cause prosopagnosia.

An fMRI study of patients with impaired face recogni-tion showed that the patients activated more posteriorareas of the fusiform gyrus than control patients, and onepatient activated left posterior fusiform gyrus more thanright [35]. The patients' face recognition performance wasstill abnormal, and it was postulated that these more pos-terior cortical areas were recruited as they used relativelyinefficient "feature-based" strategies for face perception.

ConclusionsOur understanding of the brain circuitry that underliesvisual processing beyond the primary visual cortex (area 17of Brodmann or V1 of simians) is undergoing majoradvancement, mostly with the advent of tools like PETscanning and fMRI. These tools give researchers the abilityto view the networks of brain regions that are selectively

activated as normal humans or patients perform cognitiveand perceptual activities of varying complexity.

It seems reasonably certain that this type of investiga-tion will, in the coming years, provide a wealth of newinformation about how the brain works as a highly orches-trated aggregate of local areas carrying out specific forms ofinformation processing.

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