The visual association cortex

Semir Zeki

University College London, UK

The concept of visual association cortex derives from early myelogenetic studies, assorted cases of so-called visual agnosia and much philosophical speculation. A review of the evidence suggests that it is perhaps time to

review our concept of the visual association cortex.

Current Opinion in Neurobiology 1993, 3:155-159

Introduction

The concept of association cortex is essentially a some- what vague functional concept inferred from fairly pre- cise anatomical studies. In time, philosophical specula- tion came to make its contribution to the concept, es- pecially in visual cortex. Not surprisingly, this served to confuse the concept rather than illuminate it. However that may be, the different approaches reinforced each other and led to a fundamentally flawed view of the cere- bral processes involved in vision. This supposed that the function of visual association cortex was to ‘understand what was seen, seeing being a function of the primary visual cortex, area Vl. Any revision of the concept of vi sual association cortex thus entails a profound revision of our views not only of visual cortex and the processes it undertakes, but also of our philosophical approach to the problem of vision.

Definition of visual ‘association’ cortex

The human cerebral cortex is not fully differentiated at birth. Some areas, which Flechsig [1,2] called ‘primor- dial’ and amongst which he numbered the primary visual cortex (area Vl), are myelinated at birth, though they occupy only a small fraction of the total cortical surface (Fig. 1). They are connected to the peripheral organs and are separated from each other by other, and much larger, cortical areas. The latter are not connected to the periph- eral organs and become myelinated at various stages after birth, as if their myelination depends upon the acquisi- tion of experience. Flechsig used the term ‘association’ cortex to describe these latter areas, believing them to be the Geistige Zentren or Cogitationszentren (mind centres or psychic centres). Hence, the commonly used altema- tive term for visual association cortex was the visuo-psy- chic cortex. Large cerebral areas, whose boundaries can be defined with fair precision, were thus inferred to have a function, that of association, though the function itself was not precisely delined. Was it an association of present with past records in a given modality, such as vision, or an association between different modalities that neurolo- gists had in mind? Would it be the kind of association that dignifies vision with meaning and therefore con-

scious awareness? Or was association intended to signify the unification of the representation of different points, representing different regions of the body surface, in the topographically organized sensory areas? Neurologists, assuming them to have thought about the implications of their terminology, remained vague about what they meant by the term. Instead, they proposed a definition that was so general that it applied to all the above cate- gories. They imagined that it was association cortex that gave visual ‘impressions’ their meaning and hence that it was visual association cortex which dealt with ‘higher’ functions.

F&l. Flechsig’s diagram of the medial view of the human brain, to show the primordial areas (hatched and cross-hatched) and the association areas (in white). The visual association cortex was considered to surround the primary visual cortex.

Lissauer [ 31, whose speculations were to have a powerful influence on visual neurologists, anticipated the present talk about ‘lower’ and ‘higher’ levels of vision by us- ing Leibniz’s term ‘apperception’ to speak of the func- tion of Vl in high sounding terms. Apperception was “....the highest degree of perception, in which the con- sciousness accepts the sensory impression with maximal intensity” - a view which invests Vl with a critical role in consciousness. This was followed by the process of ‘as- sociation’, of “....connecting other conceptions with the content of the perception”, thus giving them their mean- ing. But no one specified what these conceptions may

@Current Biology Ltd ISSN 0959-4388 155

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be or what underlying neural mechanisms to look for. It was suficient that lesions within Vl led to blindness, while those in the ‘visuo-psychic’ cortex led to the syn- drome of mind blindness (seelenblindheit), later termed agnosia, a condition in which a patient was deemed to be able to ‘see’ but not to ‘understand’ what was seen. This view, approved of by both Henschen and Holmes, was well summarized by Campbell [4] in 1905 when he spoke of two areas “ . ..one specialized for the pri- mary reception of visual sensations, and the other consti- tuted for the final elaboration and interpretation of these sensations”. Flechsig had believed, though without com- pelling evidence, that the role of visual association cortex was to associate visual signals with signals derived from other sources, and endowed it with a certain level of consciousness. Other neurologists, including Campbell; Holmes and Henschen, had believed, again without much evidence, that it would associate the received visual ‘im- pressions’ with similar past ‘impressions’, thus leading to ‘understanding’. By the time neurophysiologists got hold of the idea, they perpetuated the earlier views without considering the evidence, which was in any case scant. Thus, Clare and Bishop [5] studied an area well re- moved from the primary visual cortex in the cat and “inferred [it] to comprise an association area relating op- tic and acoustic activity” although no acoustic activity was studied there. In summary, these views - however much they may have differed in detail - separated the process of ‘seeing’ from that of ‘understanding’ and attributed a separate cortical seat to each. It is this fundamental con- cept that more recent work on visual ‘association’ cortex has challenged.

The challenge to the concept of association cortex

Perhaps the first step in the revision of this view came from the demonstration that the visual association cor- tex, far from being the single area which its uniform architecture and relatively late myelination had implied, consists in fact of multiple visual areas (for a review, see [6] ). This demonstration raised the possibility that the cerebral processes involved in vision are much more complex than the one implied in the dual concept of the early neurologists. The fundamental turning point came, however, with the demonstration that the visual areas of the ‘association’ cortex undertake different tasks, not the same task at ever-increasing levels of complexity, as was implicit in the earlier doctrine of exclusive hierarchies [7,8]. Thus, area V5 is specialized for visual motion [9], while area V4 is specialized for cblour and form in associ- ation with colour [l&14]. V3, by contrast, is specialized for dynamic form [ 15,161. A functional specialization is also characteristic of the prestriate cortex of man [ 171, but this is not to imply that the specializations enumer- ated above are the only functions of these areas. That the areas of the visual association cortex (now better re- ferred to as the prestriate cortex) receive parallel inputs from Vl [ 111, not only served to emphasize the fact that

the cortex undertakes several visual operations in par- allel to construct the visual image in the brain, raising the fundamental question of how the specialized visual areas interact to provide the unitary visual image in the brain, but strongly suggested that the functional segre- gation evident in prestriate cortex would be mirrored somehow in area Vl itself [ 111, even if the compelling evidence for such a supposition was to come only sev- eral years later [ 181. No one has been able to show that the cells in the above prestriate areas are influenced to any extent by stimuli belonging to another modality, say, olfactory or auditory. Equally, no one has yet been able to show that the memory of past visual experiences or stim- ulation is crucial for the activation of cells in these areas, which is not the same thing as saying that such influences may not be found to be crucial in the future. Thus, the speculations of the early neurologists, whether of Flech- sig or of Holmes, concerning the ‘understanding’ cortex do not gain much support from the current physiological profile of the visual areas of prestriate cortex.

Does visual association cortex use a fundamentally different strategy?

What is it that distinguishes the visual areas of the pre- striate cortex from area Vl? Is it a qualitative difference or a quantitative one? The single most striking feature of prestriate visual areas is their specialization. While anyone wanting to explore the functional organization of area Vl or area V2 (which surrounds it) with an electrode will encounter cells with many different properties [l’$-211, even if cells dealing with a given attribute are grouped together, the properties of cells in individual prestriate areas are more homogeneous. The cells of area V5, for example, are overwhelmingly directionally selective and uninterested in colour, whereas those of area V4 are overwhelmingly wavelength selective [ 12-15,21,22]. The initial temptation therefore would be to suppose that the role of prestriate cortex is to segregate or ‘dissociate’ signals rather than associate them. But the segregation of visual signals belonging to different sub-modalities of vi- sion is not a radically new strategy employed by the pres- mate cortex, even if it was first demonstrated there. More recent studies show that visual signals are also segregated into sub-compartments in area Vl [IS], from which the specialized areas receive their cortical input, as well as in area V2, which surrounds area Vl and projects to the same specialized visual areas [ 23-251. Hence, the segregation of visual signals in the prestriate cortex is not a novel strategy but a continuation of the strategy employed at earlier levels of the visual pathways.

The next striking feature of the prestriate areas is that, compared with the striate cortex, cells in the former have larger receptive fields. This is almost certainly the consequence of the need to collect information from larger parts of the field of view. But this is not a strat- egy developed in, or unique to, the visual areas of the prestriate cortex. Indeed it is a hallmark of the visual pathways in general. The simple cells of the striate cor-

The visual association cortex Zeki 157

tex have larger receptive fields than those of the lateral geniculate nucleus from which they receive input, and the complex cells have larger fields still [ 71. The strategy is continued well beyond the prestriate cortex, for cells in the visual areas of the inferior temporal cortex and the pati& cortex have yet larger fields (for examples, see [ 26,271). There is, next, the question of complexity in the cellular responses - itself a consequence of the enlargement of receptive fields and the collecting of information from large parts of the field of view. For example, the re- sponses of cells in V4 correlate with the perception of colours, whereas the responses of their counterparts in ~1 do not 1221; the generation of colour is itself a more complex process than the registering of the presence and intensity of different wavelengths [ 281, and to this extent the responses of V4 cells are more complex than those of Vl. Equally, the cells of area V5, or at least some of them, respond to the coherent motion of an entire ob- ject, whereas their counterparts in Vl (from which V5 receives its input) respond only to the components of which the whole is made [29]. The consequence of this is that the relevant cells of Vl may signal a direc- tion of motion which is not identical to the direction of motion of the entire object. But this complexity is not a new departure; instead it is the continuation of a pro- cess which starts in the retina itself, to the extent that the photoreceptors have simpler receptive fields and simpler responses than the ganglion cells into which they feed. In a continuation of this process, the orientation selective cells of Vl have more exigent requirements than the cells of the lateral geniculate nucleus,

The effects of cortical lesions on vision

If, therefore, the anatomical and functional profile for the prestriate cortex that we have built up over the past two decades does not suggest a radical functional departure from the kind of functional organization found in area vl, is there any plausible reason to suppose that seeing is vested in Vl and understanding in the surrounding cor- tex, apart from the fact that lesions in Vl lead to nearly complete blindness, whereas those in visual association cortex do not? Insights into this problem may be gained by a renewed study of the effects of cortical lesions on vision. I do not refer here to the carefully controlled experimental lesions in monkeys, which have been the single worst guide to the organization of the visual cor- tex imaginable, but to the natural uncontrolled lesions in human brains produced by gunshot wounds or cere- bral accidents which, paradoxically, have been a lot more informative.

That lesions in Vl, and possibly also V2 (see [30] ), should cause a total blindness is relatively easy to ex- plain - such lesions do not usually spare a given sub- compartment, for example, the blobs of Vl or the thin stripes of V2 in which cells concerned with colour are concentrated, but instead involve all compartments, The consequence is that cells dealing with all the attributes

of vision are destroyed, leading to blindness. Naturally, much the same thing would happen if all the specialized visual areas were to be destroyed. But this could only be the consequence of a lesion that is so large that it would amount to an hemispherectomy, assuming it not to have led to death.

The consequence of the more common type of lesion, one restricted to one of the specialized visual areas, is a blindness for the corresponding visual attribute. A striking example is provided by the syndrome of cere- bral achromatopsia, or acquired cortical colour blindness following lesions in area V4, which is located in the fusi- form gyrus (for a review, see [31]). No less specific is the syndrome of cerebral akinetopsia or motion imper- ception [17]. This is the consequence of lesions in area V5 [32], which is located laterally and ventrally in man and, perhaps surprisingly, in a zone (Feld 16) that Flech- sig considered to have been myelinated at birth and therefore a primordial area. But is the consequence of such lesions a radically new kind of syndrome, con- cerned with ‘understanding’ motion or colour, or is it, as the physiology suggests, a more complex example of the same phenomenon? Can meaning and understanding be attached to vision only through the participation of the visual areas of prestriate cortex, or can areas Vl and V2 contribute explicitly to both seeing and understanding the visual world?

Examination of the so-called agnosic patients, as well as patients with akinetopsia and achromatopsia, leads one to a general theory of residual vision [6]. This sup- poses that each visual area contributes explicitly to vi- sual perception (that is in a way that requires no further processing) and that the patient is able to see and to un- derstand in exact relationship to that contribution and no more. Moreover, the theory supposes that the ability to see a particular visual attribute, for example motion, is not dependent upon the integrity of the entire visual pathway, up to V5 and possibly beyond. Instead, it sup- poses that, if the latter is destroyed, the patient will be able to see visual motion in proportion to the direct and explicit contribution to vision that the intact parts of the system, including areas Vl and V2 which feed V5, are able to make. When area V5 is destroyed in an akine- topsic patient, the directionally selective cells of area Vl that feed it are not; consequently, the patient is aware of the presence of motion but cannot make much of it (see [33]). Equally, an achromatopsic patient is able to discriminate between different wavelengths, but is unable to combine this information to construct colours (see [6] ), a deficit remarkably similar to the consequence of lesions in macaque area Vd [34]. Indeed, the orien- tation selective cells of Vl, which are able to respond to pure chromatic borders [35,36], would endow an achro- matopsic patient with an intact, or partially intact, Vl, with the ability to detect the orientation of the boundary be- tween two equiluminant surfaces of different colour, even though the colours on either side of the boundary remain identical to him [ 371,

Additional support for this view comes from comparing the nature of the so-called agnosia in carbon monoxide

158 Cognitive neuroscience

patients, and in patients with large lesions in the prestri- ate cortex. It is almost certain that, in the former, area Vl is much a&ted, although of course the areas of the pres- triate cortex are probably also compromised. The conse- quence is a profound defect in form vision, with patients hardly able to recognize or copy simple geometric figures such as triangles or squares [38]. The interpretation that I have given to this syndrome is that even the elementary kind of integration and association which Vl is respon- sible for - the generation of cells especially responsive to straight lines - becomes compromised. The nature of the agnosia in patients with lesions in the prestriate cor- tex is markedly different. Now the patients can even draw complex figures, without being able to recognize the final product! Yet how is it that these patients draw? There is good agreement in the literature that the drawing is piece- meal, small segments of the picture, or of its outline - segments that the patient can see and understand - be- ing drawn, one after another. Once drawn, the patient can still only recognize small segments of his drawing and not its entirety. It is the simple components of a figure that the patients are able to see and to understand because the integrative mechanisms necessary to construct simple forms, such as lines, are intact, while those needed for more complex forms are compromised. The intact area Vl makes a direct and explicit contribution to percep- tion, but the destroyed prestriate areas are not able to perform their function and hence associate the various elements and organize into a larger whole. The patient consequently sees, understands, and is able to draw only in proportion to what his intact Vl allows him to do.

Vl is as important for conscious experience and understanding

There is, finally, the evidence from blindsight (for a re- view, see [39]), when subjects blinded by lesions in area Vl are nevertheless able to discriminate some visual stim- uli correctly, even though they commonly have no con- scious awareness of having seen anything at all. It is very likely that when such blindsight subjects detect the di- rection of motion, signals relating to motion reach area V5 directly, in the direct pathway from the lateral genicu- late nucleus to V5 [40,41]. Direct physiological evidence has shown that cells in ~5 can maintain the property of direction selectivity, although in a compromised state, af- ter ablation of V5. Yet the fact that blindsight patients have no conscious awareness of the visual stimulus, and hence no understanding of it, suggests either that pre- processing in Vl is a necessary step for stimulation to gain consciousness, or else that it is necessary for the operations performed by V5 to be referred back to Vl in the diffuse return projection linking V5 to Vl [42]. Of course, it is possible that both processes are necessary. Whatever the case, the results suggest that Vl is an essen- tial part of the process that allows conscious experience and hence understanding of vision.

Conclusion

I have concentrated in this brief review on the conceptual doctrine that we have inherited about visual ‘association’ cortex, and hence about vision, and tried to show that the separation between seeing and understanding what is seen - a concept deeply tied to that of associa- tion cortex - is not easy to achieve. One can make a fair argument - from ordinary visual perception, from anatomy and physiology, and from the study of the dam aged brain - that seeing and understanding are part of the same process, though no one would wish to deny that there are many instances in which we see things that we do not properly understand. The concept of visual association cortex, in the sense intended by the early neurologists, is therefore perhaps now best aban- doned. But, in doing so, we must acknowledge that those who originated the concept and speculated about it have a high and honourable place in the history of our subject. If the concepts that they fought for with such conviction and passion have turned about to be false, we must re- flect that the concepts that we today fight for, with no less conviction and passion, may equally turn out to be ilawed speculations in the vast ocean of the unknowns that the visual brain still is.

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S Zeki, Department of Anatomy and Developmentai Biology, University College London, Gower Street, London, WClE GBT, UK.