The discovery and analysis of cortical visual areas is a major accomplishment of visual neuroscience. In the past decade the use of noninvasive functional imaging has dramatically increased our detailed knowledge of the functional organization of the human visual cortex and its relation to visual perception.
The path leading to the discovery of the primary visual cortex can be traced back to the latter part of the eighteenth century when Francesco Gennari, a 24 year old medical student, described a clearly defined white stria within the human occipital cortex. Gennari, hardened brains with ice and with a naked eye examined the specimens. He noticed a white line in the cortex which was more obvious in the occipital lobe. The stripe of Gennari, as it was termed, is a band of nerve fibres which runs parallel to the surface of the cerebral cortex on the banks of the calcarine fissure in the occipital lobe. It is because of the presence of the stripe that this region of the brain is called the striate cortex. Gennari not only recognized that the gray matter is subdivided, but also realized that the cortex looks different in different regions of the brain. In particular, he found that the white line, which is sometimes difficult to see in sections of the frontal part of the brain can be more clearly detected in the posterior part - specifically in the region that is now known to be the primary visual cortex.
Serious experiments into cortical function began not long after the publication of Gennari's monograph. The search was on for regions that control particular functions, such as vision. The first person professing to have identified the centre for vision was the British neurologist and physiologist David Ferrier. While experimenting on monkeys, he found that stimulation of an area known as the angular gyrus, which is located in the parietal lobe, caused the eyes to move. The finding suggested to Ferrier that the angular gyrus might be the sought-after visual area of the brain. To test his idea he removed the angular gyrus and observed the response of the monkeys. Excising the gyrus from only one side of the brain seemed to leave the monkeys unable t o see in the eye opposite to the lesion; if both gyri were removed, the animals seemed to become completely blind.
Ferrier's evidence for the total loss of vision was largely anecdotal. He reported, for example, that one monkey, which was particularly fond of tea seemed unable to locate a cup placed right before its eyes. Ferrier's descriptions of the animals' activity indicate that he had unwittingly discovered not the visual centre of the brain but a region that is of major importance for the control of visually guided movement. The monkeys could no longer guide their movements according to what they saw, and that is why they had difficulty reaching food placed infront of them.
Lesions of the occipital lobe did not produce a comparable handicap; hence Ferrier had no reason to think that the occipital lobe was important for vision. Ferrier's failure to blind his monkeys by damaging the occipital lobe in both hemispheres is not hard to explain. In almost every instance he removed a large part of each lobe. This would have eliminated most of the primary visual cortex but not all of it. Even if just a few millimeters of cortex remained, the animal would have retained a good deal of its vision because relatively small amounts of the primary visual cortex map a rather large extent of the peripheral visual field.
Ferrier's conclusions were controversial. His most bitter opponent was Hermann Munk, a German professor of physiology at the Berlin Veterinary' School, who had begun his own experiments soon after Ferrier begun his. Munk correctly reported that damage to the occipital, not the parietal, lobe is responsible for blindness. He found that removal of the occipital cortex from one side of the brain made monkeys hemianopic: unable to see one side of their visual field. Because each eye lost half of its vision Munk concluded that both eyes must be connected to both the right and the left hemispheres of the brain. He also reported that removal of the occipital cortex on both sides of the brain produced total blindness.
While Ferrier pursued his studies of the angular gyrus Munk's conclusion that the occipital lobe is the seat of vision gained support. The first reasonably accurate scheme showing how the visual field is represented in the human brain was developed by a young Japanese physician named Tatsuji Inouye. The creation of Inouye's scheme was facilitated by the fact that the Russians had introduced an entirely new rifle, the Mosin-Nagant Model 9 1, which shot bullets that had a higher muzzle velocity (620 meters per second) and a smaller diameter (7.6 millimeters) than the bullets of earlier wars: the new bullets often penetrated the skull without shattering it.
Inouye based his description of the cortical map on data from 29 patients. For each patient he made a careful plot of the visual field of each eye and pinpointed the site of injury on the skull. In order to determine exactly which part of the brain was damaged, he identified each bullet's entry and exit points and calculated the area of brain that would be damaged assuming a straight trajectory through the brain tissue. Inouye's scheme revealed a fundamental fact about the organization of the striate cortex; the proportions of the image are not preserved when the image is mapped on to the cortex. Inouye did not depict the mapped proportions entirely correctly, but he did recognize that a disproportionately large fraction of the striate cortex is devoted to the central visual field, as might be expected from the fact that the macular region of the retina (the region of central focus) has a high concentration of visual cells.
In 1961, following the advancement of Inouye's scheme, Daniel and Whitteridge carried out a set of experiments on monkeys which provided data to calculate a surface that can be folded to give a close approximation to the size and folding of the visual cortex. By placing long steel electrodes at the occipital lobe and stimulating the retina via a source of light in front of the animal the researchers determined the representation of the visual field on the calcarine cortex in baboons and macaques.
The researchers defined the cortical magnification factor, in the context of visual topography, as the ratio of the difference in cortical position (in mm) to visual field position (in degrees) of a small movement of a visual stimulus. Daniel and Whitteridge stated that the linear cortical magnification factor is both locally isotropic and independent of azimuth and is thus therefore identical along the horizontal meridian and vertical meridian representations, which means that the map is both locally and globally isotropic. Thus for small angles of displacement in the visual field it appeared to be independent of the direction in which the displacement is taken. Although the magnification calculated was from a monkey and the visual acuity from humans, a positive correlation was observed - they both decreased in the peripheral field and increased in the centre.
In 1962, Hubel and Wiesel reported what was later described as “the first description of a clear function for the cerebral cortex, in terms of clear differences between input and output”. They studied the visual cortex of anaesthetized cats by stimulating light-adapted eyes with spots of white light of various shapes, stationary or moving and recording extracellularly from single cells. Hubel and Wiesel discovered that neurons in the visual cortex respond preferentially to oriented visual stimuli, rather than to the circular stimuli.
Two types of cells where found; simple and complex. Complex cells, like simple cells, prefer oriented visual stimuli. Simple cells however are picky about the position of a visual stimulus within the receptive field, while complex cells are not. In particular, simple cells have flanking excitatory and inhibitory ('on' and 'off') regions within their receptive fields where changes in light intensity have opposing effects on the cell's firing rate. Summation occurs within either type of region; when the two opposing regions are illuminated together their effects tend to cancel. But complex cells respond to a properly oriented edge regardless of its position within the receptive field. Such regions can generally not be demonstrated; but when they are the laws of summation and mutual antagonism do not apply.
Complex cells are constructed from simple cells by the convergence of inputs from many simple cells onto the complex cell. In this circuit, all of the contributing simple cells have similar orientation preferences but differ in the signs and positions of their receptive fields. This gives rise to the complex cell's lack of dependence on the position of the stimulus while maintaining orientation selectivity.
Electrical stimulation of the primary visual cortex (area V1) in humans has been shown to produce a visual percept, called a phosphene. This finding initiated a search for an effective functionally cortical visual prosthesis (CVP) that could be implantated in clinically blind individuals. In order for a CVP however to be even a remotely viable option, a permanent device for chronic stimulation of neural tissue needed to be developed.
This was accomplished in 1968 by Brindley and Lewin. The device was implanted in a 52-year-old blind woman. The device had 80 electrodes, each with its own controlling unit (radio receiver). The receivers sat directly beneath the pericranium, while the electrodes where in contact with the occipital pole of the right cerebral hemisphere.
Brindley and Lewin's device was an immediate success. By applying a voltage of about 25 V, the patient was caused to experience sensations of small points of light ('phosphenes') in the left half of the visual field. More importantly, many electrodes could be stimulated at the same time, resulting in many small points of light. The position of the electrodes corresponded roughly to the position of the phosphenes in the visual field, and the subject was able to identify patterns of phosphenes.
Of course, this device was far from ideal. One of the major problems they reported was that a single electrode could cause many phosphenes to appear or a small cloud. Sometimes this was a function of current, with a greater current leading to the production of more phosphenes, but other times it was independent of stimulus parameters. Additionally, there was a serious limitation on spatial resolution: electrodes spaced closer than 2 mm created a large strip of light when activated simultaneously. Finally, the patient reported seeing flicker in every phosphene created.
The visual brain is a remarkably efficient organ, capable of providing, within a fraction of a second, a visual image in which all the different attributes of the visual scene can be seen in precise spatiotemporal registration. The primate visual brain was first shown to consist of multiple areas in 1978 by Semir Zeki. A conclusion that was derived from the anatomical, physiological and clinical evidence was that the different areas are functionally specialised to process different attributes of the visual scene, including colour, form and motion. Zeki understood that in each cortical area the map was emphasised at a point that would be modified in that cortical area. He saw that the retinal maps were inverted at different angles at different places in the cortex and therefore named the different sites as V1, V2, V3 and V4 accordingly. He proposed probable reasons for the existence of such sites, as is the concurrent analysis of visual information at different areas which will be passed on to a more central area in a more complex fashion.
When the blood vessels that nourish the inner retina occlude the photoreceptor layer, they cast shadows onto the photoreceptors, creating angioscotomas (regions of the visual field to which that eye is blind). Remarkably, Adams and Horton have recently shown that it is sometimes possible to observe representations of these angioscotomas anatomically in the primary visual cortices of squirrel monkeys. Specifically, representations of angioscotomas where detected in 9 of 12 normal adult animals by staining flatmounts for cytochrome oxidase activity after enucleation of one eye. They appeared as thin profiles in layer 4C radiating from the blind spot representation.
Angioscotomas can be regarded as a local form of amblyopia. After birth, when light strikes the retina, photoreceptors beneath blood vessels are denied normal visual stimulation. This deprivation induces remodeling of geniculocortical afferents in a distribution that corresponds to the retinal vascular tree. Angioscotoma representations were most obvious in monkeys with fine ocular dominance columns and were invisible in monkeys with large, well segregated columns. In monkeys without columns, their width corresponded faithfully to the inducing retinal shadow, making it possible to calculate the minimum shadow required to produce a cortical representation. The "amblyogenic threshold" was calculated as the fraction of the pupil area eclipsed to trigger remodeling of geniculocortical afferents. It was found to be constant over retinal eccentricity, vessel size, and shadow size. Ambliogenic shadows only three to four cones wide were sufficient to generate a cortical representation, testifying to the remarkable precision of the cortical map.
With this rate of progress, what hope do we have for understanding what the rest of the brain is doing within another 40 years? Will experiments get easier and more productive? Some neuroscientists have lamented the changing tides of the field. Systems neuroscience lagged in the 1980s as talent and money moved increasingly toward inquiry at the molecular and cellular levels. The tide is now turning back, as researchers struggle to understand how genetic manipulations give rise to behavioural changes. The investment in molecular biology is also providing a new generation of tools for inquiry of the brain at the systems level and inspiring the excitement and optimism of future investigators. But, in the interim, a generation of visual neuroscientists has quietly chipped away at the problems, often relying on mastery of difficult technical challenges rather than the wizardry of molecular biology. The experiments described are classic examples of technical mastery at work. It is now time to endow the technical masters with the magic of wizards.