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Do humans see what monkeys see?
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ur tremendous progress in O understanding the functional Dohumanssee whatmonkeyssee? organization of the visual cortex in monkeys (e.g. see Refs 1-3) over the past 20 years has been a most impressive accomplishment in neurobiology. Partly because of the achievements in primate studies, and partly due to the impact of positron-emission tomography (PET) and other means of imaging sites of stimulus-related metabolic activity in the human brain, there has been a surge of interest and discovery related to the functional organization of the visual cortex in humans. Results obtained from monkeys and other mammals have been reported and discussed at a number of informative meetings, but a conference recently organized and conducted by Bal~izs Guly~is, Per Roland and David Ottoson ('The Functional Organization of the Human Visual Cortex, Wenner-Gren International Symposium', Stockholm, 5-7 September 1991) represented the first international conference devoted to an interchange of ideas on the organization of the visual cortex of humans. Recent discoveries from brain-imaging studies were described and discussed in conjunction with advances from anatomical, electrophysiological and histochemical studies of the human brain, and these findings were related to concepts and results from animal studies. The exchange promoted areas of consensus, pointed out uncertainties and directions for future research, and promised rapid progress in the near future. Much of the research on humans has been usefully guided by advances in animal studies. Macaque monkeys (discussed at the symposium by D. Van Essen, Pasadena, CA, USA, see Ref. 2) and other monkeys 3 have between 20 and 35 visual areas, and it would be surprising if humans did not have at least as many. In addition, monkeys and even prosimian primates clearly have at least some of these areas in common, and we would expect many of the areas of the visual cortex of monkeys to be present in humans. Furthermore, aspects of modular organization, parallel and hierarchical processnag, and even local neural circuits may be similar. TINS, Vol. 1.5, No. I, 1992
To a large extent, these expectations have been supported by evidence from humans. The primary field, VI (or area 17) was, of course, first identified in humans, and has long been considered to be present in all or most mammals. Area 17 of humans is very similar to that of monkeys in patterns of myeloarchitecture and cytoarchitecture, and in the distribution of neurotransmitters and cytochrome oxidase (discussed by M. WongRiley, Milwaukee, WI, USA; K. Zilles, Cologne, FRG; and R. Corte6s, Barcelona, Spain). PET studies indicate that area 17 is active during visual tasks, and its retinotopic organization approximates that of monkeys 4'~. Studies of degenerating thalamocortical connections in humans (J. Mikl6ssy, Lausanne, Switzerland) indicate that inputs from the lateral geniculate nucleus terminate in layers IV and VI as in monkeys, and the use of a fluorescent dye to label connections in area 17 of the postmortem human brain reveal laminar connections (A. Burkhalter, Washington, MO, USA; see also Ref. 6) that closely reflect the monkey pattern. Thus, area 17 in humans structurally resembles that of monkeys, and basic processing is likely to be similar. The development of area 17 in humans follows the pattern in monkeys, but over a longer period of time. Callosal connections are restricted to the border of area 17 in adult humans (S. Clarke, Lausanne, Switzerland, see Ref. 7), and it seems likely from studies on monkeys that this restriction occurs as a result of the initial formation of connections (C. Dehay, Bron, France, see Ref. 8). The distribution of dense puffs of cytochrome oxidase in supragranular layers emerges after birth in humans (Wong-Riley) and the intrinsic connections of superficial layers develop months after birth (Burkhalter). Thus, functions of area 17 that depend on external layers may take months to develop, while other functions based on outputs from infragranular layers may be established earlier. Probably all mammals also have a bordering field, VII, that in
monkeys forms a second, systematic (but split) representation of the hemifield 9. Because Brodmann's area 18 corresponds to VII in some primates, but is more extensive than VII in macaque monkeys and humans, a new 'area 18' needs to be defined in humans (Fig. 1). The pattern of alternating dark and light bands of cytochrome oxidase reactivity that marks the well-known sequences of three types of processing modules in monkeys I can be used to define this new area 18 with great precision in humans, since these bands clearly also exist in humans (Wong-Riley; see also Ref. 10). So far, VII has only been partially delimited in humans by more traditional Nissl and myelin preparations (Zilles; and Clarke, see Ref. 7). Because myelin stains also reveal the banding pattern in VII (Ref. 11), myelin preparations could be used to determine the banding pattern in humans. Since VII receives all three major output streams of VI in monkeys 1, VII is involved in a range of visual functions. In PET studies, VII and VI may be selectively activated by binocular depth information (B. Guly~is, Stockholm, Sweden). Another field that has been identified in a range of primate species and that appears to be part of the basic primate plan is the middle temporal visual area, MT or V5. MT is characterized by a retinotopic map, inputs from the magnocellular or M stream that are relayed from VI and VII (Ref. 1), dense myelination, and location in the upper temporal lobe. A comparable position for MT in the human brain was suggested by early PET studies using low-contrast, moving stimuli that preferentially activate the M stream (J. Watson, London, UK; see also Refs 12, 13). However, the PET studies may not accurately indicate the size of MT because of resolution limits and possibly the coactivation of adjacent areas such as the medial superior temporal area (MST) (Ref. 4). Thus, a recently described, myelin-dense field in the MT region of humans (Zilles; and Clarke, see Ref. 7) may delimit this region more precisely. Presumably, stains for degenerating
© 1992. ElsevierScience PublishersLtd, (UK) 0166-2236/921505.00
.len H. Kaas
Jon H. Kaasis at the Dept of PsycholoEy, 301 Wilson Hall, Vanderbilt University, Nashwile, TN37240, USA.
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Fig. 1. Lateral and medial views of the human brain showing proposed visual areas. The brainstem has been cut where indicated (Cut). Abbreviations: DL, dorsolateral; g., gyrus; MT, middle temporal area. (Boundaries of remote and intermediate visual regions are based on suggestions by Per Roland.)
axons in postmortem brains from which area 17 had previously been removed can provide further evidence on the exact location and retinotopic organization of MT in humans. Studies in monkeys using deoxyglucose (R. Tootell, Boston, MA, USA, see Ref. 15) reveal a system of several types of patchy modules in MT, but such features are presently below the resolution limit of imaging in humans. PET imaging studies have also been used to search for the V4 (or dorsolateral) region of monkeys in the human brain. In monkeys, the V4 region receives inputs from the two parvocellular (P) streams of VII (see Ref. 1) and provides the bulk of the relay to the ventral temporal lobe as part of the ventral processing stream described by Ungerleider and Mishkin 16 that is critical in object vision. Since the projections from VII to V4 involve neurons selective for color, while the relays directed to MT do not, V4 (and other parts of the ventral stream) should be selectively activated by color stimuli in PET experiments in humans. However, there is the complication that the V4 region is not a single area, but consists of at least two separate areas with different connections, only one of which provides the major relay into the ventral temporal cortex 17. In addition, there are major differences of opinion on the full extent of the V4 complex, and boundaries have not been unequivocally defined. Nevertheless, all investigations into the organization of the monkey cortex agree that the V4 region includes the dorsolateral visual cortex between MT and VII. Thus, if MT is similarly located in humans, the 2
expected location of at least most of V4 is in the dorsolateral cortex between MT and VII (Fig. 1). Consistent with this expectation, color stimuli were found to activate the dorsolateral occipital cortex (as well as the ventromedial cortex) in some recent PET studies 14'~s. Other PET studies with color stimuli revealed relatively selective activation only in the ventromedial cortex (Watson; see also Refs 13, 19) and this cortex in the region of the fusiform and lingual gyri was proposed to contain V4 (compare expected and proposed locations of V4 in Fig. 1). The proposed V4 region is within a larger expanse of the cortex where damage is followed by defects in color and object vision 2°. Lesions of the V4 region in monkeys produce multiple impairments, including defects in color perception (C. Heywood, Oxford, UK, see Ref. 21; and P. Schiller, Cambridge, MA, USA, see Ref. 22). Because of the different relative locations of V4 in monkeys and the proposed V4 in humans, several participants argued that the ventral region in humans is not V4. Efforts to identify other subdivisions found in the primate visual cortex with cortical areas in humans are confounded by uncertainties about how the cortex is organized in monkeys. Most notably, the cortex along the rostral border of VII has been variously described as a long belt-like area V3 with a retinotopic organization that mirrors VII (Ref. 23) - an area that is split into separate dorsal and ventral wings by V4 (Ref. 27), separate dorsal (V3d) and ventral (VP) fields that are incomplete and represent the lower or upper
visual quadrants 2, or a series of fields including VP, DL, dorsointermedial (DI), dorsomedial (DM), and M (Ref. 3). Despite these ambiguities, by assuming a particular organization in monkeys, Clarke 7 postulated the locations of V3d, VP, V3a and V4 in the human brain on the bases of postmortem callosal termination patterns and myeloarchitecture. Uncertainties also exist about possible homologues of the region involved in face recognition in the human brain (J. Sergent, Montr6al, Canada). Ventral lesions in humans involving the fusiform gyrus can produce somewhat selective impairment in the recognition of individual faces, and it has been tempting to relate this region to cortex in the banks of the superior temporal cortex where neurons are selectively responsive to faces. A. Cowey (Oxford, UK) reported that damage to the 'face area' in monkeys did not produce an impairment in face recognition, and thus differences in the effects of lesions and in relative locations constitute evidence that the regions are not homologous. Less specific comparisons do reveal basic similarities between human and monkey visual systems. The PET studies implicate large regions of cortex in visual functions (Fig. 1), and various tasks differentially activate distinct regions (A. Gjedde, Montreal, Canada; Watson; J. V. Haxby, Bethesda, MD, USA; Gulyfis; Sergent; P. Fox, San Antonio, TX, USA; and P. Roland, Stockholm, Sweden; see Refs 13, 18, 24-26). Furthermore, as in monkeys 16, there is evidence for a ventral stream of processing related to object vision and a dorsal stream TINS, VoL 15, No. 1, 1992
related to spatial aspects of vision in humans 24. Compared to monkeys, the human visual areas are more caudal, so that much of the lateral temporal lobe of humans appears to have little involvement with visual processing, although neurons responsive to visual stimuli have been recorded in the lateral temporal cortex of humans (G. Ojemann, Seattle, WA, USA). Comparisons of proposed visual areas across species would be aided by portraying human areas on a flattened surface 28 as is commonly done for monkeys 2, since in humans over half of the cortex is buried in fissures (R. Gebhardt, Dfisseldorf, FRG). The PET studies also include those with complex experimental designs that have the potential for revealing areas with higher visual functions. For example, the more remote visual regions (Fig. 1), parts of the thalamus, and frontal eye field are involved in the recall and recognition of visual patterns (Roland, see Ref. 26). Large lesions of the more remote cortical regions result in visual agnosia and impaired imagery (E. Warrington, London, UK; and M. Farah, Pittsburgh, PA, USA, see Ref. 29). The key social event of the conference was attending the Mozart opera Don Giovanni,
during which we observed complications of another sort. Because progress in understanding functional organization of the complex human visual system has been so rapid and impressive, I look forward to an updating conference (and another opera) soon. Selected references
1 DeYoe, E. A. and Van Essen, D. C. (1988) Trends Neurosci. 11,219-226 2 Felleman, D. J. and Van Essen, D. C. (1991) Cereb. Cortex 1, 1-47 3 Kaas,J. H. and Krubitzer, L. A. (1991) in Neuroanatomy of Visual Pathways and Their Retinotopic Organization (Dreher, B. and Robinson, S. R., eds), pp. 302-359, Macmillan 4 Fox, P. T. et aL (1986) Nature 323, 806-809 5 Mora, B. M., Carman, G. J. and AIIman, J. M. (1989) Trends Neurosci. 12, 282-284 6 Burkhalter, A. and Bernardo, K. L. (1989) Proc. Natl Acad. 5ci. USA 86, 1O71-1075 7 Clarke, S. and Mikl6ssy, J. (1990) J. Comp. Neurol. 298, 188-214 8 Dehay, C., Kennedy, H., Bullier, J. and Berland, M. (1988) Nature 331, 348-350 9 Cowey, A. (1964)J. NeurophysioL 27, 366-396 10 Horton, J. C., Digi, L. R., McCrane, E. P. and deMonosterio, F. M. (1990) Arch. Ophthalmol. 180, 1025-1031 11 Krubitzer, L. A. and Kaas, J. H. (1990) Visual Neurosci. 5, 165-204. 12 Miezin, F. M., Fox, P. T., Raichle, M. E. and AIIman, J. M. (1987) Soc. Neurosci. Abstr. 13, 631
13 Zeki, S. et al. (1991) J. Neurosci. 11, 641-649 14 Corbetta, M., Miezin, F. M., Dobmeyer, S., Shulman, G. L. and Petersen, S. E. (1991)J. Neurosci. 11, 2383-2402 15 Tootell, R. B. H. and Born, R. T. (1991) Soc. Neurosci. Abstr. 17, 524 16 Ungerleider, L. G. and Mishkin, M. (1982) in Analysis of Visual Behavior (Ingle, D. G., Goodale, M. A. and Mansfield, R. J. Q., eds), pp. 549-586, MIT Press 17 Steele, G. E., Weller, R. E. and Cusick, C. G. (1991). J. Comp. Neurol. 306, 495--520 18 Guly&s, B. and Roland, P. E. (1991) Neuroreport 2, 585-588 19 Lueck, C. J. et al. (1989) Nature 340, 386-389 20 Damasio, A., Yamada, T., Damasio, H., Corbett, V. and McKee, J. (1980) Neurology 30, 1064-1071 21 Heywood, C. A. and Cowey, A. (1987) J. Neurosci. 7, 2601-2617 22 Schiller, P. H. and Logothetis, N. K. (1990) Trends Neurosci. 13, 392-398 23 Sousa, A. P. B., Carmen, M., Pinon, G. P., Gattass, R. and Rosa, M. G. P. (1991) J. Comp. NeuroL 308, 665-692 24 Haxby, J. V. et al. (1991) Proc. Natl Acad. Sci. USA 88, 1621-1625 25 Petersen, S. E., Fox, P. T., Snyder, A. Z. and Raichle, M. E. (1990) Science249, 1041-1044 26 Roland, P. E., Guly&s, B., Seitz, R. J., Bohm, C. and Stone-Elander, S. (1990) Neuroreport 1, 53-56 27 Zeki, S. M. (1977) Proc. R. Soc. London Ser. B 195, 517-523 28 Gazzaniga, M. S. (1989) Science 245, 947-952 29 Farah, M. J. (1990) Visual Agnosia MIT Press
the days of Head and CorticalrelJreRntation ofpain Holmes 1, it has been known Sthatince the threshold for painful stimuli tralis posterolateralis (VPL) and thermal stimuli may be reduced, is preserved after damage to the cerebral cortex. This is in contrast to the severe changes in pain thresholds and pain sensation seen in patients with damage to the thalamus 1. These observations have led to the still widely held view that pain is sensed in the thalamus. However, it is recognized that the CNS in higher mammals can react to painful stimuli at all levels, even at the spinal level. Strong stimulation of any sense organ is painful. Besides being, for example, throbbing, burning or sharp, the perceived pain has three fundamental features: it is recognized as pain, it can be localized, and it is aversive. Most research is concerned with somesthetic pain. Strong stimulation of mechanoreceptors can be painful and excite neurons in the primate ventrobasal complex of the thalamus [the venTINS, VoL 15, No. 1, 1992
the ventralis posterior inferior (VPI) nuclei] e, but it is the spinothalamic tract that is supposed to transmit somesthetic pain and changes in temperature in particular. The spinothalamic pathway has several targets in the thalamus, which can be divided into lateral targets to the VPL, VPI, and nucleus submedius, and medial targets mainly to the intralaminar mediodorsalis (MD), centralis lateralis (CL) and parafascicularis (Pf) nuclei a'4. From the VPL and VPI the information can reach the primary somatosensory area (SI) and even the secondary somatosensory area (SII), and a few neurons in these sites have been shown to react to mechanical and thermal pain 2'5. Ablation of SI in humans is not associated with any change in the threshold for pain, although the ability to discriminate intensities of
and the patients might have trouble localizing the painful stimulus 6. It has been reported that ablation of SII in humans leaves no detectable sensory deficits7. The intralaminar neurons in the CL and Pf nuclei also react specifically to pain, but only in the awake primate ~. These neurons have high thresholds around 45°C. However, studies of somesthetic pain in awake primates are very rare. The studies conducted in anesthetized primates are inconclusive and constitute the majority of experiments carried out in this area of research. For these reasons, and because it has been impossible to find any coherent evidence for a particular cortical part or region in humans and subhuman primates to which lesions obliterate the ability to perceive pain, the role (if any) of the cortex in pain perception is still
© 1992,ElsevierSciencePublishersLtd.(UK) 0166- 2236/92/$05.00
Acknowledsements Memoryis relative and creative,so this summaryrepresents mypersonal recollection. Nevertheless,I thank PerRolandand Peter Fox for an enjoyable, informativepost. conference discussion.
PerRoland Laboratoryfor Brain Researchand PET,
KarolinskaInstitute, 8ox60400,5-10401 Stockholm,Sweden.
3
news
ur tremendous progress in O understanding the functional Dohumanssee whatmonkeyssee? organization of the visual cortex in monkeys (e.g. see Refs 1-3) over the past 20 years has been a most impressive accomplishment in neurobiology. Partly because of the achievements in primate studies, and partly due to the impact of positron-emission tomography (PET) and other means of imaging sites of stimulus-related metabolic activity in the human brain, there has been a surge of interest and discovery related to the functional organization of the visual cortex in humans. Results obtained from monkeys and other mammals have been reported and discussed at a number of informative meetings, but a conference recently organized and conducted by Bal~izs Guly~is, Per Roland and David Ottoson ('The Functional Organization of the Human Visual Cortex, Wenner-Gren International Symposium', Stockholm, 5-7 September 1991) represented the first international conference devoted to an interchange of ideas on the organization of the visual cortex of humans. Recent discoveries from brain-imaging studies were described and discussed in conjunction with advances from anatomical, electrophysiological and histochemical studies of the human brain, and these findings were related to concepts and results from animal studies. The exchange promoted areas of consensus, pointed out uncertainties and directions for future research, and promised rapid progress in the near future. Much of the research on humans has been usefully guided by advances in animal studies. Macaque monkeys (discussed at the symposium by D. Van Essen, Pasadena, CA, USA, see Ref. 2) and other monkeys 3 have between 20 and 35 visual areas, and it would be surprising if humans did not have at least as many. In addition, monkeys and even prosimian primates clearly have at least some of these areas in common, and we would expect many of the areas of the visual cortex of monkeys to be present in humans. Furthermore, aspects of modular organization, parallel and hierarchical processnag, and even local neural circuits may be similar. TINS, Vol. 1.5, No. I, 1992
To a large extent, these expectations have been supported by evidence from humans. The primary field, VI (or area 17) was, of course, first identified in humans, and has long been considered to be present in all or most mammals. Area 17 of humans is very similar to that of monkeys in patterns of myeloarchitecture and cytoarchitecture, and in the distribution of neurotransmitters and cytochrome oxidase (discussed by M. WongRiley, Milwaukee, WI, USA; K. Zilles, Cologne, FRG; and R. Corte6s, Barcelona, Spain). PET studies indicate that area 17 is active during visual tasks, and its retinotopic organization approximates that of monkeys 4'~. Studies of degenerating thalamocortical connections in humans (J. Mikl6ssy, Lausanne, Switzerland) indicate that inputs from the lateral geniculate nucleus terminate in layers IV and VI as in monkeys, and the use of a fluorescent dye to label connections in area 17 of the postmortem human brain reveal laminar connections (A. Burkhalter, Washington, MO, USA; see also Ref. 6) that closely reflect the monkey pattern. Thus, area 17 in humans structurally resembles that of monkeys, and basic processing is likely to be similar. The development of area 17 in humans follows the pattern in monkeys, but over a longer period of time. Callosal connections are restricted to the border of area 17 in adult humans (S. Clarke, Lausanne, Switzerland, see Ref. 7), and it seems likely from studies on monkeys that this restriction occurs as a result of the initial formation of connections (C. Dehay, Bron, France, see Ref. 8). The distribution of dense puffs of cytochrome oxidase in supragranular layers emerges after birth in humans (Wong-Riley) and the intrinsic connections of superficial layers develop months after birth (Burkhalter). Thus, functions of area 17 that depend on external layers may take months to develop, while other functions based on outputs from infragranular layers may be established earlier. Probably all mammals also have a bordering field, VII, that in
monkeys forms a second, systematic (but split) representation of the hemifield 9. Because Brodmann's area 18 corresponds to VII in some primates, but is more extensive than VII in macaque monkeys and humans, a new 'area 18' needs to be defined in humans (Fig. 1). The pattern of alternating dark and light bands of cytochrome oxidase reactivity that marks the well-known sequences of three types of processing modules in monkeys I can be used to define this new area 18 with great precision in humans, since these bands clearly also exist in humans (Wong-Riley; see also Ref. 10). So far, VII has only been partially delimited in humans by more traditional Nissl and myelin preparations (Zilles; and Clarke, see Ref. 7). Because myelin stains also reveal the banding pattern in VII (Ref. 11), myelin preparations could be used to determine the banding pattern in humans. Since VII receives all three major output streams of VI in monkeys 1, VII is involved in a range of visual functions. In PET studies, VII and VI may be selectively activated by binocular depth information (B. Guly~is, Stockholm, Sweden). Another field that has been identified in a range of primate species and that appears to be part of the basic primate plan is the middle temporal visual area, MT or V5. MT is characterized by a retinotopic map, inputs from the magnocellular or M stream that are relayed from VI and VII (Ref. 1), dense myelination, and location in the upper temporal lobe. A comparable position for MT in the human brain was suggested by early PET studies using low-contrast, moving stimuli that preferentially activate the M stream (J. Watson, London, UK; see also Refs 12, 13). However, the PET studies may not accurately indicate the size of MT because of resolution limits and possibly the coactivation of adjacent areas such as the medial superior temporal area (MST) (Ref. 4). Thus, a recently described, myelin-dense field in the MT region of humans (Zilles; and Clarke, see Ref. 7) may delimit this region more precisely. Presumably, stains for degenerating
© 1992. ElsevierScience PublishersLtd, (UK) 0166-2236/921505.00
.len H. Kaas
Jon H. Kaasis at the Dept of PsycholoEy, 301 Wilson Hall, Vanderbilt University, Nashwile, TN37240, USA.
I
central sulcus
~
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J
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j
J
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. , , ~ ' ~ intermediate
.
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J ,~....]..J.:=,.~expected j ~ , . . - ~ r e s uimptiv~.../o~A a~onof
l
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Fig. 1. Lateral and medial views of the human brain showing proposed visual areas. The brainstem has been cut where indicated (Cut). Abbreviations: DL, dorsolateral; g., gyrus; MT, middle temporal area. (Boundaries of remote and intermediate visual regions are based on suggestions by Per Roland.)
axons in postmortem brains from which area 17 had previously been removed can provide further evidence on the exact location and retinotopic organization of MT in humans. Studies in monkeys using deoxyglucose (R. Tootell, Boston, MA, USA, see Ref. 15) reveal a system of several types of patchy modules in MT, but such features are presently below the resolution limit of imaging in humans. PET imaging studies have also been used to search for the V4 (or dorsolateral) region of monkeys in the human brain. In monkeys, the V4 region receives inputs from the two parvocellular (P) streams of VII (see Ref. 1) and provides the bulk of the relay to the ventral temporal lobe as part of the ventral processing stream described by Ungerleider and Mishkin 16 that is critical in object vision. Since the projections from VII to V4 involve neurons selective for color, while the relays directed to MT do not, V4 (and other parts of the ventral stream) should be selectively activated by color stimuli in PET experiments in humans. However, there is the complication that the V4 region is not a single area, but consists of at least two separate areas with different connections, only one of which provides the major relay into the ventral temporal cortex 17. In addition, there are major differences of opinion on the full extent of the V4 complex, and boundaries have not been unequivocally defined. Nevertheless, all investigations into the organization of the monkey cortex agree that the V4 region includes the dorsolateral visual cortex between MT and VII. Thus, if MT is similarly located in humans, the 2
expected location of at least most of V4 is in the dorsolateral cortex between MT and VII (Fig. 1). Consistent with this expectation, color stimuli were found to activate the dorsolateral occipital cortex (as well as the ventromedial cortex) in some recent PET studies 14'~s. Other PET studies with color stimuli revealed relatively selective activation only in the ventromedial cortex (Watson; see also Refs 13, 19) and this cortex in the region of the fusiform and lingual gyri was proposed to contain V4 (compare expected and proposed locations of V4 in Fig. 1). The proposed V4 region is within a larger expanse of the cortex where damage is followed by defects in color and object vision 2°. Lesions of the V4 region in monkeys produce multiple impairments, including defects in color perception (C. Heywood, Oxford, UK, see Ref. 21; and P. Schiller, Cambridge, MA, USA, see Ref. 22). Because of the different relative locations of V4 in monkeys and the proposed V4 in humans, several participants argued that the ventral region in humans is not V4. Efforts to identify other subdivisions found in the primate visual cortex with cortical areas in humans are confounded by uncertainties about how the cortex is organized in monkeys. Most notably, the cortex along the rostral border of VII has been variously described as a long belt-like area V3 with a retinotopic organization that mirrors VII (Ref. 23) - an area that is split into separate dorsal and ventral wings by V4 (Ref. 27), separate dorsal (V3d) and ventral (VP) fields that are incomplete and represent the lower or upper
visual quadrants 2, or a series of fields including VP, DL, dorsointermedial (DI), dorsomedial (DM), and M (Ref. 3). Despite these ambiguities, by assuming a particular organization in monkeys, Clarke 7 postulated the locations of V3d, VP, V3a and V4 in the human brain on the bases of postmortem callosal termination patterns and myeloarchitecture. Uncertainties also exist about possible homologues of the region involved in face recognition in the human brain (J. Sergent, Montr6al, Canada). Ventral lesions in humans involving the fusiform gyrus can produce somewhat selective impairment in the recognition of individual faces, and it has been tempting to relate this region to cortex in the banks of the superior temporal cortex where neurons are selectively responsive to faces. A. Cowey (Oxford, UK) reported that damage to the 'face area' in monkeys did not produce an impairment in face recognition, and thus differences in the effects of lesions and in relative locations constitute evidence that the regions are not homologous. Less specific comparisons do reveal basic similarities between human and monkey visual systems. The PET studies implicate large regions of cortex in visual functions (Fig. 1), and various tasks differentially activate distinct regions (A. Gjedde, Montreal, Canada; Watson; J. V. Haxby, Bethesda, MD, USA; Gulyfis; Sergent; P. Fox, San Antonio, TX, USA; and P. Roland, Stockholm, Sweden; see Refs 13, 18, 24-26). Furthermore, as in monkeys 16, there is evidence for a ventral stream of processing related to object vision and a dorsal stream TINS, VoL 15, No. 1, 1992
related to spatial aspects of vision in humans 24. Compared to monkeys, the human visual areas are more caudal, so that much of the lateral temporal lobe of humans appears to have little involvement with visual processing, although neurons responsive to visual stimuli have been recorded in the lateral temporal cortex of humans (G. Ojemann, Seattle, WA, USA). Comparisons of proposed visual areas across species would be aided by portraying human areas on a flattened surface 28 as is commonly done for monkeys 2, since in humans over half of the cortex is buried in fissures (R. Gebhardt, Dfisseldorf, FRG). The PET studies also include those with complex experimental designs that have the potential for revealing areas with higher visual functions. For example, the more remote visual regions (Fig. 1), parts of the thalamus, and frontal eye field are involved in the recall and recognition of visual patterns (Roland, see Ref. 26). Large lesions of the more remote cortical regions result in visual agnosia and impaired imagery (E. Warrington, London, UK; and M. Farah, Pittsburgh, PA, USA, see Ref. 29). The key social event of the conference was attending the Mozart opera Don Giovanni,
during which we observed complications of another sort. Because progress in understanding functional organization of the complex human visual system has been so rapid and impressive, I look forward to an updating conference (and another opera) soon. Selected references
1 DeYoe, E. A. and Van Essen, D. C. (1988) Trends Neurosci. 11,219-226 2 Felleman, D. J. and Van Essen, D. C. (1991) Cereb. Cortex 1, 1-47 3 Kaas,J. H. and Krubitzer, L. A. (1991) in Neuroanatomy of Visual Pathways and Their Retinotopic Organization (Dreher, B. and Robinson, S. R., eds), pp. 302-359, Macmillan 4 Fox, P. T. et aL (1986) Nature 323, 806-809 5 Mora, B. M., Carman, G. J. and AIIman, J. M. (1989) Trends Neurosci. 12, 282-284 6 Burkhalter, A. and Bernardo, K. L. (1989) Proc. Natl Acad. 5ci. USA 86, 1O71-1075 7 Clarke, S. and Mikl6ssy, J. (1990) J. Comp. Neurol. 298, 188-214 8 Dehay, C., Kennedy, H., Bullier, J. and Berland, M. (1988) Nature 331, 348-350 9 Cowey, A. (1964)J. NeurophysioL 27, 366-396 10 Horton, J. C., Digi, L. R., McCrane, E. P. and deMonosterio, F. M. (1990) Arch. Ophthalmol. 180, 1025-1031 11 Krubitzer, L. A. and Kaas, J. H. (1990) Visual Neurosci. 5, 165-204. 12 Miezin, F. M., Fox, P. T., Raichle, M. E. and AIIman, J. M. (1987) Soc. Neurosci. Abstr. 13, 631
13 Zeki, S. et al. (1991) J. Neurosci. 11, 641-649 14 Corbetta, M., Miezin, F. M., Dobmeyer, S., Shulman, G. L. and Petersen, S. E. (1991)J. Neurosci. 11, 2383-2402 15 Tootell, R. B. H. and Born, R. T. (1991) Soc. Neurosci. Abstr. 17, 524 16 Ungerleider, L. G. and Mishkin, M. (1982) in Analysis of Visual Behavior (Ingle, D. G., Goodale, M. A. and Mansfield, R. J. Q., eds), pp. 549-586, MIT Press 17 Steele, G. E., Weller, R. E. and Cusick, C. G. (1991). J. Comp. Neurol. 306, 495--520 18 Guly&s, B. and Roland, P. E. (1991) Neuroreport 2, 585-588 19 Lueck, C. J. et al. (1989) Nature 340, 386-389 20 Damasio, A., Yamada, T., Damasio, H., Corbett, V. and McKee, J. (1980) Neurology 30, 1064-1071 21 Heywood, C. A. and Cowey, A. (1987) J. Neurosci. 7, 2601-2617 22 Schiller, P. H. and Logothetis, N. K. (1990) Trends Neurosci. 13, 392-398 23 Sousa, A. P. B., Carmen, M., Pinon, G. P., Gattass, R. and Rosa, M. G. P. (1991) J. Comp. NeuroL 308, 665-692 24 Haxby, J. V. et al. (1991) Proc. Natl Acad. Sci. USA 88, 1621-1625 25 Petersen, S. E., Fox, P. T., Snyder, A. Z. and Raichle, M. E. (1990) Science249, 1041-1044 26 Roland, P. E., Guly&s, B., Seitz, R. J., Bohm, C. and Stone-Elander, S. (1990) Neuroreport 1, 53-56 27 Zeki, S. M. (1977) Proc. R. Soc. London Ser. B 195, 517-523 28 Gazzaniga, M. S. (1989) Science 245, 947-952 29 Farah, M. J. (1990) Visual Agnosia MIT Press
the days of Head and CorticalrelJreRntation ofpain Holmes 1, it has been known Sthatince the threshold for painful stimuli tralis posterolateralis (VPL) and thermal stimuli may be reduced, is preserved after damage to the cerebral cortex. This is in contrast to the severe changes in pain thresholds and pain sensation seen in patients with damage to the thalamus 1. These observations have led to the still widely held view that pain is sensed in the thalamus. However, it is recognized that the CNS in higher mammals can react to painful stimuli at all levels, even at the spinal level. Strong stimulation of any sense organ is painful. Besides being, for example, throbbing, burning or sharp, the perceived pain has three fundamental features: it is recognized as pain, it can be localized, and it is aversive. Most research is concerned with somesthetic pain. Strong stimulation of mechanoreceptors can be painful and excite neurons in the primate ventrobasal complex of the thalamus [the venTINS, VoL 15, No. 1, 1992
the ventralis posterior inferior (VPI) nuclei] e, but it is the spinothalamic tract that is supposed to transmit somesthetic pain and changes in temperature in particular. The spinothalamic pathway has several targets in the thalamus, which can be divided into lateral targets to the VPL, VPI, and nucleus submedius, and medial targets mainly to the intralaminar mediodorsalis (MD), centralis lateralis (CL) and parafascicularis (Pf) nuclei a'4. From the VPL and VPI the information can reach the primary somatosensory area (SI) and even the secondary somatosensory area (SII), and a few neurons in these sites have been shown to react to mechanical and thermal pain 2'5. Ablation of SI in humans is not associated with any change in the threshold for pain, although the ability to discriminate intensities of
and the patients might have trouble localizing the painful stimulus 6. It has been reported that ablation of SII in humans leaves no detectable sensory deficits7. The intralaminar neurons in the CL and Pf nuclei also react specifically to pain, but only in the awake primate ~. These neurons have high thresholds around 45°C. However, studies of somesthetic pain in awake primates are very rare. The studies conducted in anesthetized primates are inconclusive and constitute the majority of experiments carried out in this area of research. For these reasons, and because it has been impossible to find any coherent evidence for a particular cortical part or region in humans and subhuman primates to which lesions obliterate the ability to perceive pain, the role (if any) of the cortex in pain perception is still
© 1992,ElsevierSciencePublishersLtd.(UK) 0166- 2236/92/$05.00
Acknowledsements Memoryis relative and creative,so this summaryrepresents mypersonal recollection. Nevertheless,I thank PerRolandand Peter Fox for an enjoyable, informativepost. conference discussion.
PerRoland Laboratoryfor Brain Researchand PET,
KarolinskaInstitute, 8ox60400,5-10401 Stockholm,Sweden.
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