Visual discrimination of target displacement remains after damage to the striate cortex in humans

Damage to the striate cortex usually causes blindness in those regions of the visual field which map to the area of neural damage. Nonetheless, there are reports that some patients with such damage can localize and perform certain visual discriminations between light stimuli presented within the 'blind' area of the visual field. Experiments on animals with different brain areas ablated suggest that visual function is served by two principal projection pathways from the retina. That to the striate cortex is primarily responsible for fine discrimination between stimulus parameters such as colour and spatial pattern, whereas that to the superior colliculus in the midbrain is responsible for visual localization of stimuli. The residual visual functions in patients with cortical damage are usually attributed to the non-striate retinal projection to the superior colliculus. We now present measurements of spatial discrimination in two observers with large visual field defects (scotomata) caused by damage to the striate cortical region. Both exhibit a near normal ability to discriminate displacements of targets when two lights are flashed sequentially in their defective visual field, but they are unable to discriminate spatial pattern or size. We argue that these results are consistent with the 'two visual systems' interpretation of ablation studies on non-human species.     

Formation of target-specific neuronal projections in organotypic slice cultures from rat visual cortex.

A characteristic feature of the mammalian cortex is that projection neurons located in distinct cortical layers send their axons to different targets. In visual cortex, cells in layers 2 and 3 project to other cortical areas, whereas cells in layers 5 and 6 project to subcortical targets such as the lateral geniculate nucleus. The proper development of these projections is crucial for correct functioning of the visual system. Here we show that specific connections are established in an organotypic culture system in which rat visual cortex slices are co-cultured with another slice of the visual cortex or with a thalamic slice. The laminar origin and cellular morphology in vitro of cortical projections to other cortical regions or to subcortical targets are remarkably similar to those seen in vivo. In addition, axons of projecting cells are not restricted to particular pathways, but appear instead to grow directly towards their appropriate target. These observations raise the possibility that chemotropic attraction from the target areas may play an important part in the development of the cortical projection pattern.     

Top-down signal from prefrontal cortex in executive control of memory retrieval.

Knowledge or experience is voluntarily recalled from memory by reactivation of the neural representations in the cerebral association cortex. In inferior temporal cortex, which serves as the storehouse of visual long-term memory, activation of mnemonic engrams through electric stimulation results in imagery recall in humans, and neurons can be dynamically activated by the necessity for memory recall in monkeys. Neuropsychological studies and previous split-brain experiments predicted that prefrontal cortex exerts executive control upon inferior temporal cortex in memory retrieval; however, no neuronal correlate of this process has ever been detected. Here we show evidence of the top-down signal from prefrontal cortex. In the absence of bottom-up visual inputs, single inferior temporal neurons were activated by the top-down signal, which conveyed information on semantic categorization imposed by visual stimulus-stimulus association. Behavioural performance was severely impaired with loss of the top-down signal. Control experiments confirmed that the signal was transmitted not through a subcortical but through a fronto-temporal cortical pathway. Thus, feedback projections from prefrontal cortex to the posterior association cortex appear to serve the executive control of voluntary recall.     

Visual motion and cortical velocity

Recent studies have revealed some remarkably simple relationships between visual performance and the neuroanatomy of the visual pathways. The visual field is mapped topographically on the surface of the striate cortex in man; the projection is large for the central visual field and is progressively compressed towards the periphery. Visual acuity decreases with distance from the fovea in proportion to the estimated cortical magnification factor, M (the extent of striate cortex in millimetres corresponding to a degree of arc in visual space). If a stimulus is magnified at peripheral locations in proportion to 1/M, it becomes equally resolvable across the visual field. This scaling procedure (M-scaling) maintains equivalence of the cortical projection of stimuli with different visual field loci. We have used M-scaling to investigate motion perception as a visual field variable. We report here that both the lower threshold of motion and adaptation to motion are uniform for M-scaled stimuli, and are related to the velocity of the 'cortical image'.     

Wavelength sensitivity in blindsight

Blindsight--the residual visual functions observed in visualfield defects resulting from destruction of part of the primary visual cortex (striate cortex) even though visual stimuli presented in the field defect are not consciously perceived--has generated new insights into the nature of consciousness and the role of the extrastriate pathways in visual processing. Some patients can detect and localize unseen stimuli when they are required to guess. Discrimination of movement, flicker and orientation may also be present, but residual colour discrimination is controversial. Negative results imply that only the pathways from eye to striate cortex can transmit information about colour in primates. By measuring sensitivity to light of different wavelengths in patients with blindsight we show that spectral sensitivity in the blind fields is surprisingly high, with a reduction of only 1 log unit or less across the visible spectrum. It is also essentially normal in form, whether the patients are adapted to light or dark. The shift in peak sensitivity from medium to shorter wavelengths in adaptation to the dark (the Purkinje shift) and the presence of discontinuities in the light-adapted curve together show that blindsight involves both rod and cone contributions, and that some colour opponency remains. As colour opponency requires input from primate beta retinal ganglion cells, two-thirds of which degenerate transneurally after a striate cortical lesion in juvenile monkeys, our results show that the surviving subpopulation of primate beta cells is functional.     

Mixed parvocellular and magnocellular geniculate signals in visual area V4.

Visual information from the retina is transmitted to the cerebral cortex by way of the lateral geniculate nucleus (LGN) in the thalamus. In primates, most of the retinal ganglion cells that project to the LGN belong to one of two classes, P and M, whose axons terminate in the parvocellular or magnocellular subdivisions of the LGN. These cell classes give rise to two channels that have been distinguished anatomically, physiologically and behaviourally. The visual cortex also can be subdivided into two pathways, one specialized for motion processing and the other for colour and form information. Several lines of indirect evidence have suggested a close correspondence between the subcortical and cortical pathways, such that the M channel provides input to the motion pathway and the P channel drives the colour/form pathway. This hypothesis was tested directly by selectively inactivating either the magnocellular or parvocellular subdivision of the LGN and recording the effects on visual responses in the cortex. We have previously reported that, in accordance with the hypothesis, responses in the motion pathway in the cortex depend primarily on magnocellular LGN. We now report that in the colour/form pathway, visual responses depend on both P and M input. These results argue against a simple correspondence between the subcortical and cortical pathways.     

Calbindin immunoreactivity alternates with cytochrome c-oxidase-rich zones in some layers of the primate visual cortex

Calcium ions have a pivotal role in many neuronal activities, but little is known about their involvement in the cortical processing of visual information. Using immunohistochemical methods, we have now detected a calcium-binding protein, calbindin-D-28K, which may confer on certain compartments of cortical area 17 the ability to modulate Ca2+ metabolism. Thus, calbindin occurs in the primate striate cortex in a pattern almost complementary to that displaying strong cytochrome c-oxidase activity. From this and other observations, we deduce that the distribution of calbindin-immunoreactive sites corresponds mainly to extra-geniculocortical connections of the primary visual cortex. This implies that the geniculocortical and extra-geniculocortical compartments of area 17 differ in an intracellular system for Ca2+ homeostasis.     

Receptive field dynamics in adult primary visual cortex.

The adult brain has a remarkable ability to adjust to changes in sensory input. Removal of afferent input to the somatosensory, auditory, motor or visual cortex results in a marked change of cortical topography. Changes in sensory activity can, over a period of months, alter receptive field size and cortical topography. Here we remove visual input by focal binocular retinal lesions and record from the same cortical sites before and within minutes after making the lesion and find immediate striking increases in receptive field size for cortical cells with receptive fields near the edge of the retinal scotoma. After a few months even the cortical areas that were initially silenced by the lesion recover visual activity, representing retinotopic loci surrounding the lesion. At the level of the lateral geniculate nucleus, which provides the visual input to the striate cortex, a large silent region remains. Furthermore, anatomical studies show that the spread of geniculocortical afferents is insufficient to account for the cortical recovery. The results indicate that the topographic reorganization within the cortex was largely due to synaptic changes intrinsic to the cortex, perhaps through the plexus of long-range horizontal connections.     

Ocular dominance shift in kitten visual cortex caused by imbalance in retinal electrical activity

Monocular lid suture during the sensitive period early in the life of a kitten disrupts normal development of inputs from the two eyes to the visual cortex, causing a decrease in the fraction of cortical cells responding to the deprived eye. Such an ocular dominance shift has been assumed to depend on patterned visual experience, because no change in cortical physiology is produced by inequalities between the two eyes in retinal illumination or temporally modulated diffuse light stimulation. A higher-level process, involving gating signals from areas outside striate cortex, has been proposed to ensure that sustained changes in synaptic efficacy occur only in response to behaviourally significant visual inputs. To test whether such a process is necessary for ocular dominance plasticity, we treated 4-week-old kittens with visual deprivation and monocular tetrodotoxin (TTX) injections to create an imbalance in the electrical activities of the two retinas in the absence of patterned vision. After 1 week of treatment we determined the ocular dominance distribution of single units in primary visual cortex. In all kittens studied, a significant ocular dominance shift was found. In addition to this physiological change, there was an anatomical change in the lateral geniculate nucleus, where cells were larger in laminae receiving input from the more active eye. Our results indicate that patterned vision is not necessary for visual cortical plasticity, and that an imbalance in spontaneous retinal activity alone can produce a significant ocular dominance shift.     

A comparison of inhibition in orientation and spatial frequency selectivity of cat visual cortex

Neurones in the visual cortex are highly selective for orientation and spatial frequency of visual stimuli. There is strong neurophysiological evidence that orientation selectivity is enhanced by inhibitory interconnections between columns in the cortex which have different orientation sensitivities, an idea which is supported by experiments using neuropharmacological manipulation or complex visual stimuli. It has also been proposed that selectivity for spatial frequency is mediated in part by a similar mechanism to that for orientation, although evidence for this is based on special use of visual stimuli, which hampers interpretation of the findings. We have therefore examined selectivity for both orientation and spatial frequency using a technique which allows direct inferences about inhibitory processes. Our method uses microiontophoresis of an excitatory amino acid to elevate maintained discharge of single neurones in the visual cortex. We then present visual stimuli both within and outside the range of orientations and spatial frequencies which cause a cell to respond with increased discharge. Our results show that orientations presented on either side of the responsive range usually produce clear suppression of maintained discharge. In marked contrast, spatial frequencies shown to either side of the responsive range have little or no effect on maintained activity. We conclude that there is an intracortical organization of inhibitory connections between cells tuned to different orientations but not different spatial frequencies.     

Different time courses of learning-related activity in the prefrontal cortex and striatum

To navigate our complex world, our brains have evolved a sophisticated ability to quickly learn arbitrary rules such as 'stop at red'. Studies in monkeys using a laboratory test of this capacity--conditional association learning--have revealed that frontal lobe structures (including the prefrontal cortex) as well as subcortical nuclei of the basal ganglia are involved in such learning. Neural correlates of associative learning have been observed in both brain regions, but whether or not these regions have unique functions is unclear, as they have typically been studied separately using different tasks. Here we show that during associative learning in monkeys, neural activity in these areas changes at different rates: the striatum (an input structure of the basal ganglia) showed rapid, almost bistable, changes compared with a slower trend in the prefrontal cortex that was more in accordance with slow improvements in behavioural performance. Also, pre-saccadic activity began progressively earlier in the striatum but not in the prefrontal cortex as learning took place. These results support the hypothesis that rewarded associations are first identified by the basal ganglia, the output of which 'trains' slower learning mechanisms in the frontal cortex.     

Modulation of visual cortical plasticity by acetylcholine and noradrenaline

During a critical period of postnatal development, the temporary closure of one eye in kittens will permanently shift the ocular dominance (OD) of neurones in the striate cortex to the eye that remains open. The OD plasticity can be substantially reduced if the cortex is infused continuously with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) during the period of monocular deprivation, an effect that has been attributed to selective depletion of cortical noradrenaline. However, several other methods causing noradrenaline (NA) depletion leave the plasticity intact. Here we present a possible explanation for the conflicting results. Combined destruction of the cortical noradrenergic and cholinergic innervations reduces the physiological response to monocular deprivation although lesions of either system alone are ineffective. We also find that 6-OHDA can interfere directly with the action of acetylcholine (ACh) on cortical neurones. Taken together, our results suggest that intracortical 6-OHDA disrupts plasticity by interfering with both cholinergic and noradrenergic transmission and raise the possibility that ACh and NA facilitate synaptic modifications in the striate cortex by a common molecular mechanism.     

The colour centre in the cerebral cortex of man

Anatomical and physiological studies have shown that there is an area specialized for the processing of colour (area V4) in the prestriate cortex of macaque monkey brain. Earlier this century, suggestive clinical evidence for a colour centre in the brain of man was dismissed because of the association of other visual defects with the defects in colour vision. However, since the demonstration of functional specialization in the macaque cortex, the question of a colour centre in man has been reinvestigated, based on patients with similar lesions in the visual cortex. In order to study the colour centre in normal human subjects, we used the technique of positron emission tomography (PET), which measures increases in blood flow resulting from increased activity in the cerebral cortex. A comparison of the results of PET scans of subjects viewing multi-coloured and black-and-white displays has identified a region of normal human cerebral cortex specialized for colour vision.     

A neurological dissociation between perceiving objects and grasping them

Studies of the visual capacity of neurological patients have provided evidence for a dissociation between the perceptual report of a visual stimulus and the ability to direct spatially accurate movements toward that stimulus. Some patients with damage to the parietal lobe, for example, are unable to reach accurately towards visual targets that they unequivocally report seeing. Conversely, some patients with extensive damage to primary visual cortex can make accurate pointing movements or saccades toward a stimulus presented in their 'blind' scotoma. But in investigations of visuomotor control in patients with visual disorders, little consideration has been given to complex acts such as manual prehension. Grasping a three-dimensional object requires knowledge not only of the object's spatial location, but also of its form, orientation and size. We have examined a patient with a profound disorder in the perception of such object qualities. Our quantitative analyses demonstrate strikingly accurate guidance of hand and finger movements directed at the very objects whose qualities she fails to perceive. These data suggest that the neural substrates for the visual perception of object qualities such as shape, orientation and size are distinct from those underlying the use of those qualities in the control of manual skills.     

Subtractive and divisive adaptation in the human visual system.

Sensory systems can adapt to the conditions imposed on them. In the visual system, adapting to a pattern increases the threshold of the ability to see that pattern, and reduces the perceived contrast of the pattern above threshold. Most neurons of the striate cortex reduce their responsiveness after being stimulated for some time by a high-contrast pattern. Such an effect may lie behind these psychophysical adaptation phenomena. These adaptation effects have been reported to be confined to patterns of similar orientation, which is understandable in that the visual neurons that adapt are only excited by a small range of orientations. Neurophysiological evidence suggests that neurons with different orientation preferences have inhibitory interconnections. It is therefore of interest to explore the possible effects of these connections on perception. Here we show that adapting to a horizontal pattern can reduce the perceived contrast of a vertical test pattern more than a horizontal test pattern. These 'cross-orientation' effects are modelled by a division-like process, whereas the more normal 'similar-orientation' effects are modelled by a subtractive process.     

Direct visuomotor transformations for reaching

The posterior parietal cortex (PPC) is thought to have a function in the sensorimotor transformations that underlie visually guided reaching, as damage to the PPC can result in difficulty reaching to visual targets in the absence of specific visual or motor deficits. This function is supported by findings that PPC neurons in monkeys are modulated by the direction of hand movement, as well as by visual, eye position and limb position signals. The PPC could transform visual target locations from retinal coordinates to hand-centred coordinates by combining sensory signals in a serial manner to yield a body-centred representation of target location, and then subtracting the body-centred location of the hand. We report here that in dorsal area 5 of the PPC, remembered target locations are coded with respect to both the eye and hand. This suggests that the PPC transforms target locations directly between these two reference frames. Data obtained in the adjacent parietal reach region (PRR) indicate that this transformation may be achieved by vectorially subtracting hand location from target location, with both locations represented in eye-centred coordinates.     

An evolutionary scaling law for the primate visual system and its basis in cortical function

A hallmark of mammalian brain evolution is the disproportionate increase in neocortical size as compared with subcortical structures. Because primary visual cortex (V1) is the most thoroughly understood cortical region, the visual system provides an excellent model in which to investigate the evolutionary expansion of neocortex. I have compared the numbers of neurons in the visual thalamus (lateral geniculate nucleus; LGN) and area V1 across primate species. Here I find that the number of V1 neurons increases as the 3/2 power of the number of LGN neurons. As a consequence of this scaling law, the human, for example, uses four times as many V1 neurons per LGN neuron (356) to process visual information as does a tarsier (87). I argue that the 3/2 power relationship is a natural consequence of the organization of V1, together with the requirement that spatial resolution in V1 should parallel the maximum resolution provided by the LGN. The additional observation that thalamus/neocortex follows the same evolutionary scaling law as LGN/V1 may suggest that neocortex generally conforms to the same organizational principle as V1.     

Masking unveils pre-amodal completion representation in visual search

When one object is partly occluded by another, its occluded parts are perceptually 'filled in', that is, the occluded object appears to continue behind its occluder. This process is known as amodal completion. The completion of a partially occluded object takes about 200 ms, and pre-completion information (that is, information from before amodal completion has occurred) exists in the visual system for that duration. It has been suggested, however, that observers cannot make use of this information, even when it is beneficial to do so: visual search for a target that appears to be partly occluded, for example, is slower than for a target that does not undergo occlusion, despite both targets being physically identical. Here we show that visual search does have access to pre-completion representations, but only for a limited time that depends on the size of the occluded region.     

Visual behaviour mediated by retinal projections directed to the auditory pathway

An unresolved issue in cortical development concerns the relative contributions of intrinsic and extrinsic factors to the functional specification of different cortical areas. Ferrets in which retinal projections are redirected neonatally to the auditory thalamus have visually responsive cells in auditory thalamus and cortex, form a retinotopic map in auditory cortex and have visual receptive field properties in auditory cortex that are typical of cells in visual cortex. Here we report that this cross-modal projection and its representation in auditory cortex can mediate visual behaviour. When light stimuli are presented in the portion of the visual field that is 'seen' only by this projection, 'rewired' ferrets respond as though they perceive the stimuli to be visual rather than auditory. Thus the perceptual modality of a neocortical region is instructed to a significant extent by its extrinsic inputs. In addition, gratings of different spatial frequencies can be discriminated by the rewired pathway, although the grating acuity is lower than that of the normal visual pathway.     

Effect of impulse blockage on cytochrome oxidase activity in monkey visual system

Cytochrome oxidase (cytochrome c oxidase; ferrocytochrome c: oxygen oxidoreductase, EC 1.9.2.1) has been introduced as an oxidative metabolic marker for neurones in the central nervous system. Previous studies have shown that mature neurones remained sensitive to altered functional demands, and that both developing and adult neurones responded to sensory deprivation or deafferentation by reducing their cytochrome oxidase (Cyt. Ox.) activity. More recently, we showed that the blockage of retinal impulse transmission with tetrodotoxin led to a reversible reduction in Cyt. Ox. staining of affected lateral geniculate (LGN) and striate neurones in adult cats. The present study sought to extend these findings to adult monkeys, where Cyt. Ox. 'puffs' or 'blobs' are uniquely present in the visual cortex. We found that, while the retina remained histologically intact, with only moderate decreases in Cyt. Ox. staining of large ganglion cells and the two plexiform layers, subtle changes occurred in the LGN as early as 1 day post-tetrodotoxin injection, and clear reduction in enzyme levels was evident in both the LGN and the visual cortex by 3 days. Changes became progressively more severe up to 4 weeks post-injection. Within area 17, alternating bands of high and low Cyt. Ox. staining occurred in lamina IV, with alternating rows of dark and lightly reactive puffs superimposed in exact register. Thus, the mature visual neurones in the primate remain extremely sensitive to the cessation of retinal impulse transmission, and plastic metabolic changes occur through several synapses along the sensory pathway.