Ординатура / Офтальмология / Английские материалы / The Neuropsychology of Vision_Fahle, Greenlee_2003

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contribution of one of these methodologies, lesions of visual neurons, to our understanding of the function of the visual pathways. The literature on such inactivation is extensive, and earlier work has already been reviewed (Gross 1973; Dean 1982). Our analysis will emphasize more recent studies that have examined the effects of striate and extrastriate lesions in the primate.

Methods of inactivation

There are many techniques for inactivating neural tissue, some permanent and some transitory, and each has its own advantages and disadvantages. Permanent lesions are made by aspiration, thermocoagulation, or injections of neurotoxic agents. Of these methods, the use of neurotoxic agents, such as ibotenic acid, is by far the most preferred, since it permits the creation of cell-body-specific lesions that spare fibres of passage (Schwarcz et al. 1979). This approach has proven important in regions of the nervous system where damaging fibres of passage may contribute to the observed deficit (Meunier et al. 1999). An important advantage of permanent inactivation is that the lesion is morphologically stable over a long period of time. This makes it possible to determine the precise extent and severity of the lesion after completion of the experiment by histological mapping (e.g. Yamasaki and Wurtz 1991) or by MRI (Pasternak and Merigan 1994; Merigan 2000). This stability also avoids the complex time course that can occur with pharmacological inactivations as cortex returns to normal after an injection, or if repeated injections produce diminishing inactivation. On the other hand, a potential disadvantage of permanent lesions is that the nervous system could reorganize in response to the lesion, resulting in a change in the magnitude or the nature of the induced deficit (e.g. Newsome and Paré 1988; Yamasaki and Wurtz 1991; Rudolph and Pasternak 1999). Another limitation of neurotoxic lesions is that to inactivate very large areas of the brain (e.g. inferotemporal cortex) would require an impractically large number of injections. For such inactivations, aspiration (e.g. Huxlin et al. 2000b) or cooling (see below) is more common. The majority of studies of the perceptual effects of neural inactivation in the macaque have used permanent lesions.

Transitory inactivation of nervous tissue is typically achieved by the local injection of pharmacological blocking agents that affect only cell bodies, such as muscimol (Dias and Segraves 1999; Li et al. 1999; Martin and Ghez 1999) or -aminobutyric acid (GABA; Malpeli 1999). Other commonly used reversible methods of inactivation, such as injections of lidocaine (Malpeli 1999) and the application of cold to the cortical surface (e.g. Fuster et al. 1981; Horel et al. 1984; Quintana et al. 1989), are less selective, since they inactivate both cell bodies and fibres. These methods offer rapid and reversible inactivation of neural tissue, with recovery within minutes after GABA and lidocaine injections, and after hours with muscimol injection, and a time course controlled by the investigator in the application of cold. Such transitory inactivation is used to minimize the problem of reorganization in the nervous system, because the time of inactivation can be quite brief. This method is also advantageous because control observations can be taken just

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before, and in some cases again just after, the inactivation. Such controls are important in examining perceptual effects, because visual performance is often practice-dependent and, when control observations are taken before the lesion is made, the postlesion observations often involve a more experienced, or in some cases, a more discouraged, subject. One limitation of the use of pharmacological methods is that the area inactivated by a single injection is relatively small (Hupé et al. 1999; Malpeli 1999) and extending this region requires multiple injections at different locations. Another limitation is the relatively short duration of the effect, which limits the length of the testing sessions and extent of psychophysical measures. A methodological concern with cooling studies is that a gradient of partial cooling extends from the site of targeted cooling, and it is important to determine if this gradient, which sometimes reaches cells that were meant to be spared from inactivation, contributes to the neural deficit. Although temporary inactivation has been extensively used to study the visual system (e.g. Malpeli et al. 1981; Girard et al. 1991; Ferrera et al. 1994a), there are few instances in which it has been used to study perceptual effects in macaques.

Methodological concerns in lesion studies

The use of lesions to study brain organization has a long and productive history, with many of the first insights into the function of different brain regions resulting from lesion studies (e.g. Cowey and Gross 1970; Passingham 1972; Kluver and Bucy 1997). However, lesions remain a controversial approach to understanding neural function (Gregory 1961; Dean 1982), perhaps because it appears counterintuitive to explore the function of a complex system by damaging it (think of studying the function of an audio-amplifier by removing resistors). Fortunately, careful design of the lesion study, and sensitivity to potential errors in interpretation can help in making lesion studies informative. On the other hand, because of the complexity of experimental protocols used to study lesion effects, it is easy to mistakenly either overestimate or underestimate the perceptual role of the missing neurons.

Underestimation of the effects of a lesion

Underestimation of the effects of a neural lesion can result from only partial damage to a cortical area or recovery from a lesion due to reorganization of the brain. Incomplete lesions will produce minimal lesion effects if the spared neurons can mediate the tested abilities. This can be particularly critical when lesions are made in retinotopic areas, since survival of a small region could give quite normal function in some parts of the visual field. A good solution to this problem is to make lesions over only a portion of the visual field, and then confine stimulus presentation to the affected region, by using controlled fixation. The visual field extent of the lesion can be verified by physiological recording (Merigan et al. 1991) or by behavioural mapping (Merigan and Pham 1998).

Substantial, and in some cases complete, recovery of function has been reported after brain lesions at a variety of locations including the oculomotor system (Schiller et al.

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1980), the somatosensory system (Merzenich et al. 1983), and the extrastriate cortical visual system (Newsome and Paré 1988; Rudolph and Pasternak 1999). This recovery may include several factors that evolve over time. First, there is often a recovery of local neural processing that immediately follows the lesion, suggesting an unmasking of preexisting functional connections (Das and Gilbert 1995). Following this, there can be an improvement over the first few days after the lesion that may be due to resolution of the oedema, gliosis, and acute nerve injury that follow a lesion (Horgan and Finn 1997). Finally, there is often a long-term (sometimes practice-dependent) reorganization of the nervous system that can substitute for the function of the lesioned area (Florence and Kaas 1995; Eysel and Schweigart 1999).

Overestimation of the effects of a lesion

Overestimation of the effects of a cortical lesion could be due to unintended damage to neurons beyond those targeted, or to a profound, but non-specific, change in some more general aspect of neural function. There can be unintended damage to neighbouring cortical areas, if the lesion extends beyond the planned size. It is also possible to inadvertently lesion fibres passing through or near a lesioned area. A particularly important example of this is unintended damage to optic radiation fibres caused by experimental lesions of parietal or temporal cortex in macaques, or by stroke or neurosurgery in human patients. The extent of optic radiation damage can be assessed by examining degeneration in the lateral geniculate nucleus (LGN; Ungerleider and Brody 1977; Huxlin et al. 2000b), and such degeneration is often substantial. If degeneration in the LGN is present, it could cause scattered dense scotomata across the visual field, making interpretation of parietal or temporal lobe lesions difficult.

A second way in which lesions can cause an overestimate of the role of a cortical region in a given perceptual function is by causing a generalized and non-specific change in the behaviour used to evaluate neural function. Such unwanted effects as loss of motivation, impaired motor function, or attentional deficits must be ruled out before other interpretations of neural lesions can be made. This can best be done by using a range of perceptual tasks and stimuli—some likely to be affected by the lesion and some likely to be spared.

Early visual cortex

Area V1

Primary visual cortex (also known as striate cortex or V1), is the first cortical stage of the primate visual pathways, and the recipient of the great majority of fibres from the retinogeniculate pathway. This is a very large cortical area with precise retinotopy, and has the smallest RFs of any visual cortical area (Hubel and Wiesel 1968). V1 neurons show several emergent selectivities (properties not seen at earlier stages of the visual system) such as orientation, direction, and disparity tuning. In addition, orientationand colour-tuned

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cells are grouped within V1 in orientation columns and blobs, respectively (Hubel et al. 1976). A small number of fibres from the retinogeniculate pathway bypass V1 and terminate directly in V2 (Bullier and Kennedy 1983; also see Chapter 3, this volume and Fig. 5.1). There are also minor projections from subcortical structures, such as the pulvinar, that bypass V1 and project directly to extrastriate cortical areas (Levitt et al. 1995), and such fibres may help mediate residual function after lesions of area V1.

Although the anatomical segregation of neural classes that becomes the ventral and dorsal streams (see Fig. 5.1) begins in area V1, these pathways are closely intertwined within V1 (Lund 1988; Casagrande 1994), and lesion studies have not had the precision to tease apart their functional contribution. Thus, V1 lesions affect both pathways producing a profound effect on visual performance, leading to regions of the visual field that have such dense loss of vision that they are termed scotomata. Most of the studies described in this section of the review have tried to determine the characteristics of any slight residual vision within these scotomata.

That V1 lesions cause severe visual loss was first discovered in human subjects, in whom head injuries suffered in the Russo–Japanese war of 1905 or the First World War of 1917 caused visual field defects (e.g. Glickstein 1988; Grusser and Landis 1991; Glickstein and Fahle 2000). Such defects rarely show substantial change in extent or density over the succeeding years. Monkey studies also show severe visual loss after V1 lesions (Weiskrantz and Cowey 1967; Miller et al. 1980; Merigan et al. 1993), although the completeness of this loss was questioned after some monkeys with V1 lesions appeared to orient toward visual stimuli (e.g. Humphrey and Weiskrantz 1967; see Chapter 9, this volume). Recent interest in the effects of V1 lesions has been generated largely by two developments—the growing recognition that humans may show some residual vision (termed ‘blindsight’) after V1 lesions (Weiskrantz 1986) and the observation of activity in extrastriate cortical areas after lesions of striate cortex in monkeys and humans (Rodman et al. 1989; Ffytche et al. 1996).

The interpretation of many macaque studies of the effects of V1 lesions is aided by histological verification that V1 was completely destroyed (e.g. Miller et al. 1980), and that the LGN showed no evidence of spared sectors (some remaining cells in the LGN are to be expected, given that neurons in this nucleus project to other targets besides striate cortex). Such evidence is not available for humans with ‘blindsight’, making interpretation of their residual vision more uncertain. In macaque studies, following complete (i.e. histologically verified) removal of the striate cortex, the profound visual loss is accompanied by survival of some rudimentary vision. Destriated monkeys can detect rapid flicker (Humphrey and Weiskrantz 1967; Chapter 9, this volume), discriminate blue from yellow and red from green (Schilder et al. 1972; Keating 1979), track moving lights (Humphrey and Weiskrantz 1967), discriminate simple forms (Keating and Horel 1976; Dineen and Keating 1981), and even successively grasp two objects placed side by side (Humphrey and Weiskrantz 1967; see Chapter 9, this volume). However interesting these residual abilities are, of course, they represent minor sparing in a virtually complete loss of vision.

Studies of residual vision in humans after striate cortex lesions (Grusser and Landis 1991) show many of the same surviving visual abilities as shown in the above studies in

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monkeys. For example, subjects can make eye movements (Poppel 1973) or reach (Weiskrantz 1986) towards punctate targets, they show some preservation of motion thresholds, especially in peripheral vision, they can discriminate large changes in stimulus orientation (Weiskrantz 1986), and they can detect stimuli on the basis of chromatic change (Stoerig and Cowey 1992).

It is likely that different visual pathways are responsible for different aspects of the minimal vision that survives V1 lesions. For example, the minimal colour vision that survives V1 lesions may depend on colour-opponent neurons, making it likely that this ability reflects the function of primate beta ganglion cells projecting through the pulvinar (Cowey et al. 1994). On the other hand, coarse localization after V1 lesions may be maintained by non-colour-opponent cortical projections from the superior colliculus (Walker et al. 1995). There is also evidence that in monkeys with V1 lesions, light–dark discrimination, one of the simplest possible visual tasks, can be maintained even by a very minimal visual pathway, the accessory optic tract (Pasik and Pasik 1973).

Area V2

Area V2 is a large cortical area that receives most of its ascending input from area V1, and sends substantial projections to areas V3, middle temporal (MT), and V4. This area consists of a series of elongated regions that can be labelled by cytochrome oxidase (Olavarria and Van Essen 1997) or the antibody Cat 301 (Deyoe et al. 1990) and that are termed thick, thin, and interstripes. The thick stripes appear to be an early component of the dorsal pathway, and they contain cells projecting to area MT that are selective for direction of motion and disparity (Shipp and Zeki 1985; Roe and Tso 1997; see Chapter 3, this volume). The thin stripes and interstripes are seen as an early component of the ventral stream, show selectivity for colour and orientation, and project to area V4 (Felleman et al. 1997), but some fibres project directly to TEO bypassing V4 (Nakamura et al. 1993a). Physiological RFs in V2 are larger than in V1, and some response properties are more complex than those of V1. For example, V2 cells respond well to illusory contour stimuli (von der Heydt and Peterhans 1989) and to stimuli of moderately complex form (Kobatake and Tanaka 1994).

Numerous earlier studies have described lesions made in prestriate cortex, of which V2 is a component (i.e. anterior to area V1). However, this is a difficult region to study with lesions, because it consists of several highly retinotopic areas (V2, V3, V3a, and V4), and the extent of damage to each of these areas, as well as possible sparing of some portion of the visual field of each area, cannot be determined without physiological mapping. A second problem is that, in the macaque, area V2 is closely apposed to area V1, representing the same portion of the visual field, making it almost impossible to lesion area V2 without partially lesioning area V1. The best solution to this problem is to physiologically map the damage to V1 and V2, and place test stimuli in a part of the visual field that corresponds to complete V2 damage, with no V1 damage (Merigan et al. 1993).

One study that was able to verify that visual testing was done only within the affected part of the visual field in V2 (Merigan et al. 1993), found results consistent with the

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and most likely disrupting both ventral and dorsal pathways. However, as can be seen in Fig. 5.1, there is a large projection from V1 directly to MT that might be partly responsible for the spared sensitivity for the direction of grating motion after V2 lesions. V2 lesions also profoundly disrupted two complex form discriminations—one discrimination that involved the collinearity of dots and another that required perceptual grouping of line segments (Fig. 5.3(a), (b)). These disruptions of moderately complex spatial perception were retinotopically matched to the location and extent of the lesion, appeared permanent, and could not be accounted for by the small reduction in visual sensitivity. This profile of visual loss, combined with the selective disruption of visual sensitivity, suggests comparison to the ventral pathway lesions described below.

Ventral pathway

The ventral pathway has been termed the ‘colour and form’ pathway (Maunsell and Newsome 1987) because both colour and shape selectivity are prominent in the physiological responses of V4 (Zeki 1983b; Desimone et al. 1985; Kobatake and Tanaka 1994) and inferotemporal (IT) cortex neurons (Gross et al. 1969; Tanaka 1992), the two major components of the ventral pathway. This section will provide an overview of the perceptual effects of lesions in these two areas.

Like areas V1 and V2, area V4 is a highly retinotopic cortical area, although the receptive fields of its neurons are larger and slightly more irregular than those of areas V1 and V2 (Lennie 1998). As mentioned above, the thinand interstripes of V2 project to V4, and there is some evidence of a modular organization within V4 that reflects these inputs (Xiao et al. 1999). However, to date, no lesion studies have had the precision to separately study these modules.

Perception of simple forms: stimulus orientation

This section summarizes the growing evidence that V4 and IT lesions can elevate thresholds for some simple form discriminations. This evidence may appear at odds with earlier conclusions that midand high-level ventral pathway lesions produce minimal, if any, effects on many basic visual thresholds, as well as on physiologically measured evoked responses in areas V1 and V2 (Dean 1975; Kulikowski et al. 1994; Cowey et al. 1998).

Merigan (1996) examined the effects of V4 lesions on contrast thresholds for detection and discrimination of the orientation and direction of motion of simple sinusoidal gratings (see Fig. 5.2). While orientation discrimination thresholds were elevated, direction discrimination thresholds were not affected. The stimuli used in this study to test orientation thresholds were stationary with a slow onset, whereas those used to test direction thresholds drifted at 10 /s. Subsequently, detection thresholds were also measured for the low and high temporal frequency stimuli, and V4 lesions affected only the low temporal frequency thresholds. This selective deficit for thresholds measured with low temporal frequency gratings may be a reflection of damage to projections from parvocellular neurons, which are highly responsive to low temporal frequencies (Merigan and Maunsell 1993) and which are normally present in area V4 (Ferrera et al. 1994b).

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Later, Rudolph and Pasternak (1999) explicitly studied the selectivity of V4 and MT lesions for orientation versus direction discriminations measured with both higher and lower spatial and temporal frequencies. They found that V4 lesions resulted in deficits in contrast thresholds for discriminating orientation (Fig. 5.4), while those for discriminating the direction of motion of gratings of the same spatial and temporal frequencies were unaffected (Fig. 5.5). The elevation of thresholds for orientation discrimination was most pronounced at higher spatial and lower temporal frequencies. Thus, V4 lesion effects were limited to orientation discrimination measured with lower temporal and higher spatial frequency gratings. These authors also found elevated signal/noise ratios for orientation, but not direction, discrimination when the gratings were masked by spatial noise (Fig. 5.5). Schiller and Lee (1994) also measured the effects of V4 lesions on contrast thresholds with luminance and chromatic checkerboards (draughtboards), rather than with gratings, and found a sensitivity deficit.

A similar selectivity for contrast sensitivity measured with orientation thresholds versus direction thresholds was seen by Merigan after bilateral IT lesions (Fig. 5.6). Again, contrast thresholds for orientation discrimination were markedly affected by the lesion, while those measured with direction discrimination were intact. This result suggests that, like V4 lesions, area IT lesions may also selectively disrupt orientation discriminations. It is noteworthy that, in an earlier study, IT lesions did not appear to affect contrast thresholds when the monkeys were required only to detect the presence of the grating, rather than to identify its orientation (Cowey et al. 1998).

The effects of lesions of the ventral pathway on the precision of orientation discrimination have been studied by several groups. DeWeerd et al. (1996) examined orientation difference thresholds in monkeys with longstanding V4 lesions, and found elevations of thresholds for gratings defined by texture and by illusory contours. Deficits for luminance-defined gratings were either absent or very small. A similar observation that orientation difference thresholds for luminance gratings are spared by V4 lesions was made by Rudolph and Pasternak (1999).

Relatively modest deficits in the accuracy of orientation discrimination have also been observed following lesions of IT cortex. Dean (1978) used luminance-defined gratings to examine orientation difference thresholds in monkeys with IT lesions and found consistent threshold elevations. In a more recent study, Vogels et al. (1997) tested orientation discrimination in monkeys with unilateral IT lesions involving areas TE and TEO, combined with transection of callosal connections. Orientation discrimination was measured with two tasks—one involving the comparison of simultaneously presented orientations and the other the comparison of successively presented oriented stimuli. The accuracy of orientation discrimination measured in a simultaneous discrimination paradigm was largely unaffected. However, when orientation discrimination was measured with the task that required the monkeys to remember the orientation of a previously presented stimulus, area IT lesions caused a great disruption.