Comparison of the effects of striate cortex and retinal lesions on visual acuity in the monkey.

Acuity falls sharply and predictably in man as fixation is shifted away from the test stimulus. If the same "eccentricity" function applies to the monkey, then it can be shown that striate cortex lesions produce a smaller acuity impairment than is predicted by electrophysiological maps of the projection of retina onto the cortex. It is seen in this study that retinal lesions of the fovea and adjacent parafovea produce a more severe drop in acuity than corresponding cortical lesions, and therefore the surprisingly slight effects of the latter cannot be explained in terms of a relatively higher parafoveal acuity in the monkey. The discrepancy between retinal and cortical effects is unlikely to be due to the development of "supersensitivity" at the edge of the cortical lesions. An explanation is proposed in terms of lateral spread of information at retinal and/or geniculate stages of the visual system.

Segregation of visual selection and saccades in human frontal eye fields.

The premotor theory of attention suggests that target processing and generation of a saccade to the target are interdependent. Temporally precise transcranial magnetic stimulation (TMS) was delivered over the human frontal eye fields, the area most frequently associated with the premotor theory in association with eye movements, while subjects performed a visually instructed pro-/antisaccade task. Visual analysis and saccade preparation were clearly separated in time, as indicated by 2 distinct time points of TMS delivery that resulted in elevated saccade latencies. These results show that visual analysis and saccade preparation, although frequently enacted together, are dissociable processes.

Remembering John Newsom-Davis' contribution to human imaging in Oxford.

John Newsom-Davis played a crucial role in supporting areas of scientific exploration beyond his own research interests. In particular, he was one of the key players in establishing human neuroimaging in Oxford. Here, we celebrate the role that he played in this endeavour, both in the early days of pulling together funding, and solving practical challenges, and in the following years, when we all appreciated his ongoing encouragement and support.

Visual awareness: still at sea with seeing?

Recent experiments clarify the role of the primary visual cortex and other cortical areas in visual awareness and blindsight.

Now you see it, now you don't. Colour vision.

Studies of patients who are colour blind as a result of brain damage show that colour contributes much more to our perception of the visual world than merely the registration of hue.

The neurobiology of blindsight.

Some patients can respond to visual stimuli presented within their clinically absolute visual field defects that have been caused by partial destruction of striate cortex. This puzzling phenomenon of looking, pointing, detecting and discriminating without seeing has been called blindsight, and has fascinated philosophers and neuroscientists alike as a spotlight on the nature of unconscious or covert awareness, and the means it provides of studying the visual information carried by pathways other than the major route through the striate cortex.

Magnetic stimulation studies of visual cognition.

The panoply of non-invasive techniques for brain imaging is responsible for much of the current excitement in cognitive neuroscience; sensory, perceptual and cognitive behaviour can now be correlated with cerebral blood flow as assessed by functional imaging, the electrical fields generated by populations of neurons or changes in magnetic fields created by electrical activity. Correlations between localized brain activity and behaviour, however, do not of themselves establish that any brain area is necessary for a particular task; necessity is the domain of the lesion technique. Transcranial magnetic stimulation (TMS) is a technique that can be used non-invasively to produce reversible functional disruption and has already been used to investigate visual detection, discrimination, attention and plasticity. The power of TMS as a `lesion' technique lies in the opportunity to combine reversible disruption with high degrees of spatial and temporal resolution. In this review we trace some of the major developments in the use of TMS as a technique for the investigation of visual cognition.

Cerebral achromatopsia: colour blindness despite wavelength processing.

Cortical colour blindness is caused by brain damage to the ventro-medial occipital and temporal lobes. A possible explanation is that the pathway responsible for transmitting information about wavelength and its subsequent elaboration as colour has been destroyed at the cortical level. However, several signs of chromatic processing persist in an achromatopsic subject who, despite his inability to tell colours apart, can still detect chromatic borders, perceive shape from colour, and discriminate the direction in which a striped pattern moves when the determination of direction requires the viewer to 'know' which stripes have a particular colour. Perhaps only the information about wavelength that leads to conscious awareness of colour has been destroyed. It is unclear whether incomplete achromatopsia is merely a less severe form of the disorder or whether it is qualitatively different, perhaps reflecting impaired colour constancy. In monkeys, removing cortical area V4 impairs performance on colour constancy tasks but, invariably, impairs several other aspects of visual perception. If the lesion that causes total achromatopsia in human subjects corresponds to area V4 in monkeys, it is an unsolved puzzle that a totally achromatopsic subject paradoxically demonstrates certain characteristics of colour constancy, unless his residual performance reflects the much underrated retinal contribution to colour constancy.

Chromatic Discrimination in a Cortically Colour Blind Observer.

We tested the ability of a subject with cerebral achromatopsia to discriminate between colours and to detect chromatic borders. He was unable to identify colours or to arrange them in an orderly series or choose the odd colour out of an array or even to pick out a colour embedded in an array of greys. Nevertheless, he could select the odd colour when the colours were contiguous, even when they were isoluminant, and could discriminate an ordered from a disordered chromatic series as long as the colours in each row abutted one other. His verbal replies showed that he did so by detecting an edge between two stimuli that were, to him, perceptually identical. Introducing a narrow isoluminant grey stripe between adjacent colours abolished or greatly impaired this ability. As long as isoluminant colours were contiguous the patient could identify the orientation of the chromatic borders. Photopic spectral sensitivity showed evidence both for activity of three cone channels and for chromatic opponent processing, indicating that postreceptoral chromatic processing is occurring despite the absence of any conscious awareness of colour. The results indicate that both parvocellular colour opponent and magnocellular broad-band channels are active and that the cortical brain damage has selectively disrupted the appreciation of colour but not the ability to detect even isoluminant chromatic borders, which would be invisible to a retinal achromat. The subject's performance on non-colour tasks involving the discrimination of shape, texture, greyness and position was excellent. His disorder is therefore not like that of macaque monkeys in which cortical area V4 has been removed, and which are much more severely impaired at discriminating shape than colour.

Immunoreactivity for Taurine Characterizes Subsets of Glia, GABAergic and non-GABAergic Neurons in the Neo- and Archicortex of the Rat, Cat and Rhesus Monkey: Comparison with Immunoreactivity for Homocysteic Acid.

The cerebral cortex is an area rich in taurine (2-aminoethanesulphonic acid), but only limited information exists regarding its cellular distribution. We therefore examined taurine-like immunoreactivity in the cerebral cortex of the rat, cat and macaque monkey using antiserum directed against glutaraldehyde-conjugated taurine. Immunostaining was assessed at the light and electron microscopic level, and patterns obtained in light microscopic studies were compared to those produced with antiserum to gamma-aminobutyric acid (GABA) and homocysteic acid (HCA). In all three species, strong taurine-like immunoreactive perivascular endothelial cells, pericytes and oligodendrocytes were found. These cells were located throughout the neuropil, which itself showed a low level of immunoreactivity. In rats and cats, a small number of weakly taurine-enriched neurons were observed, particularly in superficial layers. In all cortical areas of the macaque, however, glial staining was matched by strong, selective staining of subpopulations of cortical neurons which were distributed in a bilaminar pattern involving layers II/III and VI. In addition, in primary visual cortex, area 17, immunopositive neurons were also present in sublayer IVCbeta, while in the hippocampus strongly taurine-positive neurons were most conspicuous in the granule cell layer of the dentate gyrus. In all regions, strongly taurine-positive neurons constituted only a subpopulation of the neurons occupying a given layer. Examination of adjacent sections for GABA immunoreactivity showed that the most strongly taurine-positive neurons in layers II/III were immunoreactive for GABA. The cells located in layers IVCbeta and VI, and the granule cells of the dentate gyrus, however, were GABA-negative. The morphological features of these latter groups suggested that the antiserum to taurine identifies subsets of spiny stellate, small pyramidal and dentate granule cells. None of these neurons showed immunoreactivity with antiserum to HCA in the primate; HCA-positive glia were found along the pial and white matter boundaries of the cortex, and showed no overlap with strongly taurine-positive glial elements. Although a transmitter role for taurine may be unlikely, particularly in view of its enrichment in subpopulations of both inhibitory and excitatory cells, the capacity of taurine to influence membrane-associated functions in excitable tissues, and its selective distribution demonstrated here, provides the potential for a contribution to communication between cortical cells.

Combined Golgi and electron microscopic study on the synapses formed by double bouquet cells in the visual cortex of the cat and monkey.

The morphology of certain Golgi-stained cells was examined in the striate and peristriate cortex of the cat and in the striate cortex of the rhesus monkey. Neurons in layer III were selected on the basis of their characteristic vertical axon bundles, which are 20-150 microns in diameter and traverse layers II-V. Selected neurons were examined under the electron microscope to characterize their synapses and to establish their postsynaptic targets. It was found that double bouquet cells form symmetrical or type II synapses. In the cat the postsynaptic membrane specialization was more extensive than in the monkey. After removing the Golgi precipitate from boutons of two cells in the cat, small pleomorphic and flattened vesicles were found in the boutons. Earlier suggestions that double bouquet cells make synapses preferentially with spines of apical dendrites could not be confirmed. Out of 66 boutons in area 17 of the cat, 86.4% formed synapses with dendritic shafts, many of them belonging to nonpyramidal cells, 9% with perikarya of nonpyramidal cells, and only 4.6% with spines. Out of 19 synapses examined in area 18, 74% were contacting dendritic shafts and the rest contacted spines. In the monkey 60% of a total of 35 double bouquet cell synapses made synapses with dendritic shafts. A different type of double bouquet cell with densely spiny dendrites is also described in layer IV of the monkey striate cortex. This neuron formed asymmetrical synapses. It is suggested that layer III double bouquet cells with vertical axon bundles are probably inhibitory and act on other nonpyramidal cells and certain parts of pyramidal cells.

Fibre organization of the monkey's optic tract: II. Noncongruent representation of the two half-retinae.

The representations of the two half-retinae were examined in the monkey's optic tract. Intravitreal injections of tritiated amino acids were made to reveal the distributions of the crossed and uncrossed populations of optic axons, while localized implants of horseradish peroxidase (HRP) were made into different regions of the optic tract in order to examine the distributions and morphological types of retrogradely labelled cells at corresponding loci in the two half-retinae. Crossed and uncrossed optic axons are intermingled throughout most of the optic tract, but uncrossed axons are very sparse or absent along both the deep and superficial extremes of the tract. Implants of HRP into the deeper regions of the tract demonstrate that the crossed and uncrossed optic axons of the P beta retinal ganglion cells are slightly out of binocular registration, with the uncrossed map being shifted to a slightly superficial location relative to the crossed map. The optic axons for the remaining cell classes, revealed by implants of HRP into the superficial portion of the tract, are much more conspicuously out of binocular registration (in particular, the P alpha optic axons); but in their cases, the uncrossed optic axons are shifted to deeper locations relative to the crossed optic axons. Further evidence that these optic axon classes are markedly out of binocular registration comes from the two optic tracts of a bilaterally destriated monkey, in which most of the P beta optic axons have undergone a transneuronal retrograde degeneration. Following a uni-ocular injection of tritiated amino acids, the distributions of the remaining crossed and uncrossed axonal labelling occupied different positions within the tract rather than being intermingled, with the uncrossed optic axons situated deep to the majority of crossed optic axons. These results demonstrate that the optic chiasm does not combine binocularly corresponding optic axons of similar type. They also demonstrate that noncongruent field defects should be a common consequence of damage to the optic tract in humans. If the fibre order in the mammalian optic tract arises as a consequence of the sequence of axonal addition during development, then differences in the relative times of genesis for nasal and temporal members of any cell class, and/or differences in the relative pathlengths between the eye and two optic tracts, may produce the fibre ordering described herein.

Fibre organization of the monkey's optic tract: I. Segregation of functionally distinct optic axons.

The fibre organization of the monkey's optic tract was examined by implanting pellets of horseradish peroxidase into different locations within the tract, or into the superior colliculus and pretectum. Retinae were examined for the distribution, size, and morphological types of retrogradely labelled ganglion cells; optic tracts were examined for the distribution of anterogradely and retrogradely labelled axonal profiles; and lateral geniculate nuclei were examined for the distribution of anterogradely labelled processes within distinct geniculate laminae. Localized implants in the optic tract produced retrograde labelling of ganglion cells across wide regions of the retinal surface. The maximum density of labelled cells was always substantially less than the total ganglion cell density known to be present at those retinal loci. Distinct retinal ganglion cell types were labelled from differing regions within the optic tract: implants into the deep (dorsal) portion of the tract, far removed from the outer, pial, surface, retrogradely labelled predominantly P beta retinal ganglion cells, whereas implants into the superficial (ventral), subpial, part of the tract retrogradely labelled primarily the other retinal ganglion cell types, i.e., the P alpha, P gamma, and P epsilon cells. Within any given class of axon, there is a mapping of the centroperipheral retinal axis across the deep-to-superficial dimension of the tract, but this retinotopy is extremely coarse. Anterograde labelling of axonal terminations within the lateral geniculate nucleus showed a corresponding specificity for distinct geniculate laminae, the deep implants labelling the parvocellular laminae, superficial implants labelling the magnocellular laminae. Implants into the visual centres of the midbrain produced retrograde axonal labelling rostral to the lateral geniculate nucleus only in the superficial part of the optic tract. These results demonstrate that the monkey's optic tract is not a simple topographic mapping of retinal eccentricity. Rather, the primary organizational principle is that of a segregation of functionally distinct optic axon classes. As fibre order in the mammalian optic tract is also a chronological index of axonal arrival during development, the present results provide specific predictions about the temporal order of ganglion call genesis and axonal addition within the visual pathway. They also provide an anatomical basis for the functionally selective visual impairments that may arise following local damage to the optic tract in humans.

The role of the corpus callosum and extra striate visual areas in stereoacuity in macaque monkeys.

Stereoacuity was measured in six normal male rhesus monkeys by requiring them to indicate the closer of two vertical line targets. Their stereoacuity ranged from 13-23 arc sec and was as good as that of human observers tested in the same way. Sectioning the splenium of the corpus callosum, either before or after removing the foveal representation in visual area 2, had no effect on stereoacuity thresholds, indicating that the splenium is not essential for the detection of small retinal disparities at the visual mid-line. In contrast, removal of the foveal representation in V2 permanently and markedly elevated stereoacuity thresholds, almost to the level observed in two monkeys after removal of the representation in striate cortex of the central 5 degrees of the retina. Posterior infero-temporal ablation also impaired stereoacuity, though less strikingly. In these two monkeys, the effect of subsequent damage to the rostral superior colliculi was examined. One animal was unimpaired. In the other, in which the pre-tectum was damaged, the stereoacuity threshold was substantially raised, most plausibly as a consequence of imperfect binocular fixation.

Visual detection in monkeys with blindsight.

Monkeys with unilateral striate cortical removal show residual visual abilities in their affected hemifield. To learn whether the monkeys, like patients with blindsight, lose the phenomenal representation of the visual stimuli they nevertheless respond to, we first studied their ability to localize a briefly presented target in either hemifield. By varying the luminance of the stimuli we determined their visual sensitivity, which was reduced by 0.3-1.5 log units in the impaired hemifield; suprathreshold stimuli yielded almost perfect performance. We then presented two tests designed to show whether the monkeys categorized visual stimuli in the impaired field in the same manner as they categorize them in the normal field. In the first test, they had to respond differently according to whether one or two lights were presented, with the relative position of the two stimuli in a pair being varied. Whenever one of the paired stimuli lay in the impaired hemifield, two of the three monkeys consistently ignored it, and responded as if it had been a single stimulus in the good field. In the second test, trials consisting of a single stimulus light were interleaved with blank trials. The monkey touched the position of the light or made a different response, indicating that no light had appeared. All three monkeys responded to a light of supra-threshold luminance presented in the impaired field as if it were a blank trial. These results suggest that monkeys with striate cortical destruction, like neurological patients with similar lesions, have blindsight rather than phenomenal vision when they have to detect brief static visual targets.

How lateralised is visuospatial neglect?

Seventeen patients with left visuospatial neglect caused by cerebral infarction undertook the six subtests of the Behavioural Inattention Test (BIT) as soon as possible following their neurological event. The group mean results on line, letter and star cancellation tasks revealed a linear decrement in performance from right to left on the displays. However, subsequent analysis of patients' cancellations revealed that this finding was not representative of individual performance. Many patients in fact made both marked left- and right-sided omissions on the three cancellation tasks. This was not merely a transitory phenomenon because it remained present at weekly follow-up intervals. Patients' performance on a laterally extended version of the star cancellation task was also investigated. These findings strongly suggest that patients with visuospatial neglect can initially present with a diverse range of performance deficit. Many patients, in particular those with the lowest BIT scores, showed a consistent pattern in the results on letter and star cancellation, providing evidence that their inattention consistently included a considerable section of right-sided (including the extreme right of displays) as well as left-sided space.

Left visuo-spatial neglect can be worse in far than in near space.

We tested five patients with marked left-sided visuo-spatial neglect and two control subjects on a test of line bisection. A series of horizontal lines was presented to each subject, who had to indicate the centre with a projection light-pen. All five patients misplaced the centre to the right, in accordance with their left-sided neglect. However, in all five the angular displacement was greater for lines well beyond reach, than for lines of identical angular size within reaching distance. This result, precisely because it is opposite to that of a previous report, supports the conclusion that there are separate dissociated neural systems concerned with the perception of, and response to, stimuli in near and far space.

Defensive responses to looming visual stimuli in monkeys with unilateral striate cortex ablation.

A number of residual visual functions including detection, localization and discrimination of visual stimuli, have been demonstrated in the "blind" fields of monkeys and human patients following damage to striate cortex. We report here that avoidance movements of the head can also be elicited from monkeys with unilateral striate cortex ablations when a "looming" stimulus is presented within the hemianopic and presumably "blind" field. The possible role of the retinofugal projection to superior colliculus in the mediation of these defensive head movements is discussed.

Blindness to form from motion despite intact static form perception and motion detection.

We studied the motion perception, including form and meaning generated by motion, in a hemianopic patient who also had visual perceptual impairments in her seeing hemifield as a result of a lesion in ventral extrastriate cortex. She was unable to recognise 2- or 3-dimensional forms, and even borders, generated by motion alone, failed to recognise mimed actions or the Johannson 'biological motion' display, and ceased to recognise people well-known to her when they moved. Her performance with static displays, although impaired, could not explain her inability to perceive shape or derive meaning from moving displays. Unlike a motion-blind patient, she can still see and describe the motion, with the exception of second-order motion, but not what it creates or represents.

Temporal aspects of visual search studied by transcranial magnetic stimulation.

Transcranial magnetic stimulation was applied over the parietal visual cortex of subjects while they were performing 'pop-out' or conjunction visual search tasks in arrays containing eight distractors. Magnetic stimulation had no detrimental effect on the performance of pop-out search, but did significantly increase reaction times on conjunction search when stimulation was applied over the right parietal cortex 100 msec after the onset of the visual display for trials when the target was present. Target absent reaction times were elevated when stimulation was applied 160 msec after array onset. Stimulation had no effect on the number of errors made. The results suggest that a sub-region of the right parietal lobe is important for conjunction search but not for pre-attentive pop-out. The result from target present trials is consistent with timing data from studies of single cells in monkeys and the hypothesis that parietal areas generate a signal that projects back to extrastriate visual areas to enhance the processing of features in a restricted part of the visual field. The timing of the effect indicates that transcranial stimulation disrupts the mechanisms underlying the focal attention necessary for feature binding in conjunction search. The effects of TMS on target absent trials are interpreted in terms of fronto-parietal connections and the role of frontal cortex in decision-making. The results also highlight the efficacy of transcranial magnetic stimulation as a complement to other spatial and temporal imaging techniques.