Evidence for the existence and development of visual inhibition in humans

Neural inhibition forms a major mechanism by which the nervous system refines and elaborates its input. Several recent experiments have demonstrated the existence of inhibition between orientation-selective cells of the primary visual cortex of the cat and although the precise function of this inhibition is uncertain, there is evidence that it enhances orientation tuning and that it is involved in pattern recognition. Here we report a series of experiments which, on the basis of evoked potential responses to oriented stimuli, suggest that similar processes may exist in humans. Recordings from young infants further suggest that the machinery which mediates orientation-specific interactions may not be functional at birth, but develops only after 6-8 months.     

Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns

The mammalian cortex is organized in a columnar fashion: neurons lying below each other from the pia to the white matter usually share many functional properties. Across the cortical surface, cells with similar response properties are also clustered together, forming elongated bands or patches. Some response properties, such as orientation preference in the visual cortex, change gradually across the cortical surface forming 'orientation maps'. To determine the precise layout of iso-orientation domains, knowledge of responses not only to one but to many stimulus orientations is essential. Therefore, the exact depiction of orientation maps has been hampered by technical difficulties and remained controversial for almost thirty years. Here we use in vivo optical imaging based on intrinsic signals to gather information on the responses of a piece of cortex to gratings in many different orientations. This complete set of responses then provides detailed information on the structure of the orientation map in a large patch of cortex from area 18 of the cat. We find that cortical regions that respond best to one orientation form highly ordered patches rather than elongated bands. These iso-orientation patches are organized around 'orientation centres', producing pinwheel-like patterns in which the orientation preference of cells is changing continuously across the cortex. We have also analysed our data for fast changes in orientation preference and find that these 'fractures' are limited to the orientation centres. The pinwheels and orientation centres are such a prominent organizational feature that it should be important to understand their development as well as their function in the processing of visual information.     

Experience with moving visual stimuli drives the early development of cortical direction selectivity

The onset of vision occurs when neural circuits in the visual cortex are immature, lacking both the full complement of connections and the response selectivity that defines functional maturity. Direction-selective responses are particularly vulnerable to the effects of early visual deprivation, but it remains unclear how stimulus-driven neural activity guides the emergence of cortical direction selectivity. Here we report observations from a motion training protocol that allowed us to monitor the impact of experience on the development of direction-selective responses in visually naive ferrets. Using intrinsic signal imaging techniques, we found that training with a single axis of motion induced the rapid emergence of direction columns that were confined to cortical regions preferentially activated by the training stimulus. Using two-photon calcium imaging techniques, we found that single neurons in visually naive animals exhibited weak directional biases and lacked the strong local coherence in the spatial organization of direction preference that was evident in mature animals. Training with a moving stimulus, but not with a flashed stimulus, strengthened the direction-selective responses of individual neurons and preferentially reversed the direction biases of neurons that deviated from their neighbours. Both effects contributed to an increase in local coherence. We conclude that early experience with moving visual stimuli drives the rapid emergence of direction-selective responses in the visual cortex.     

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.     

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.     

Endstopped neurons in the visual cortex as a substrate for calculating curvature

Neurons in the visual cortex typically respond selectively to the orientation, and velocity and direction of movement, of moving-bar stimuli. These responses are generally thought to provide information about the orientation and position of lines and edges in the visual field. Some cells are also endstopped, that is selective for bars of specific lengths. Hubel and Wiesel first observed that endstopped hypercomplex cells could respond to curved stimuli and suggested they might be involved in detection of curvature, but the exact relationship between endstopping and curvature has never been determined. We present here a mathematical model relating endstopping to curvature in which the difference in response of two simple cells gives rise to endstopping and varies in proportion to curvature. We also provide physiological evidence that endstopped cells in area 17 of the cat visual cortex are selective for curvature, whereas non-endstopped cells are not, and that some are selective for the sign of curvature. The prevailing view of edge and curve determination is that orientations are selected locally by the class of simple cortical cells and then integrated to form global curves. We have developed a computational theory of orientation selection which shows that measurements of orientation obtained by simple cells are not sufficient because there will be strong, incorrect responses from cells whose receptive fields (RFs) span distinct curves (Fig. 1). If estimates of curvature are available, however, these inappropriate responses can be eliminated. Curvature provides the key to structuring the network that underlies our theory and distinguishes it from previous lateral inhibition schemes.     

Effects of grouping in contextual modulation.

Perception of a visual target and the responses of cortical neurons can be strongly influenced by a context surrounding the target. This observation relates to the fundamental issue of how cortical neurons code objects of the external world. In high-contrast regimes, embedding a target in an iso-oriented context reduces neural responses and deteriorates performance in psychophysical experiments. Performance from orthogonal surrounds is better than that from iso-oriented ones. This contextual interference is often postulated to be caused by long- or short-range interactions between neurons tuned to orientation. Here we show, using a new illusion called 'shine-through' as a sensitive psychophysical probe, that the orientation difference between target and context does not determine performance. Instead, contextual modulation depends on the overall spatial structure of the context. We propose that contextual suppression vanishes if the contextual elements are grouped to an independent and coherent object.     

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.     

Imaging cortical correlates of illusion in early visual cortex

Exploring visual illusions reveals fundamental principles of cortical processing. Illusory motion perception of non-moving stimuli was described almost a century ago by Gestalt psychologists. However, the underlying neuronal mechanisms remain unknown. To explore cortical mechanisms underlying the 'line-motion' illusion, we used real-time optical imaging, which is highly sensitive to subthreshold activity. We examined, in the visual cortex of the anaesthetized cat, responses to five stimuli: a stationary small square and a long bar; a moving square; a drawn-out bar; and the well-known line-motion illusion, a stationary square briefly preceding a long stationary bar presentation. Whereas flashing the bar alone evoked the expected localized, short latency and high amplitude activity patterns, presenting a square 60-100 ms before a bar induced the dynamic activity patterns resembling that of fast movement. The preceding square, even though physically non-moving, created gradually propagating subthreshold cortical activity that must contribute to illusory motion, because it was indistinguishable from cortical representations of real motion in this area. These findings demonstrate the effect of spatio-temporal patterns of subthreshold synaptic potentials on cortical processing and the shaping of perception.     

Control of visual cortical signals by prefrontal dopamine

The prefrontal cortex is thought to modulate sensory signals in posterior cortices during top-down attention, but little is known about the underlying neural circuitry. Experimental and clinical evidence indicate that prefrontal dopamine has an important role in cognitive functions, acting predominantly through D1 receptors. Here we show that dopamine D1 receptors mediate prefrontal control of signals in the visual cortex of macaques (Macaca mulatta). We pharmacologically altered D1-receptor-mediated activity in the frontal eye field of the prefrontal cortex and measured the effect on the responses of neurons in area V4 of the visual cortex. This manipulation was sufficient to enhance the magnitude, the orientation selectivity and the reliability of V4 visual responses to an extent comparable with the known effects of top-down attention. The enhancement of V4 signals was restricted to neurons with response fields overlapping the part of visual space affected by the D1 receptor manipulation. Altering either D1- or D2-receptor-mediated frontal eye field activity increased saccadic target selection but the D2 receptor manipulation did not enhance V4 signals. Our results identify a role for D1 receptors in mediating the control of visual cortical signals by the prefrontal cortex and suggest how processing in sensory areas could be altered in mental disorders involving prefrontal dopamine.     

Vernier acuity of neurones in cat visual cortex

The ability of human observers to detect Vernier breaks of as little as 5 s arc has been termed hyperacuity as this distance is substantially less than the angular separation of the bars of the highest spatial frequency of grating (approximately 1 arc min) that can be detected. Although the visual cortex is a likely candidate for the location of detectors involved in this performance, it is not known whether there are cells sensitive enough to detect deviations from co-linearity that are small compared with their spatial resolution (defined in terms of the highest spatial frequency that the cell can detect). We report here the results of physiological experiments on single units in area 17 of the cat visual cortex in which we studied the effect of introducing a Vernier break into a bar stimulus moved across the receptive field of the cell at a constant velocity. Our results show that the responses of most simple and complex cells are significantly reduced by the introduction of a Vernier break that is substantially smaller than the spatial resolution of the cell. The most sensitive cells in our sample could discriminate Vernier offsets of 3-6 arc min with a reliability of approximately 70%. This was much smaller than their spatial resolution, which was in the range 25-30 arc min. We interpret these results in terms of mechanisms that could underly the orientation selectivity of cortical neurones and suggest how our results relate to human Vernier acuity.     

Influence of the thalamus on spatial visual processing in frontal cortex

Each of our movements activates our own sensory receptors, and therefore keeping track of self-movement is a necessary part of analysing sensory input. One way in which the brain keeps track of self-movement is by monitoring an internal copy, or corollary discharge, of motor commands. This concept could explain why we perceive a stable visual world despite our frequent quick, or saccadic, eye movements: corollary discharge about each saccade would permit the visual system to ignore saccade-induced visual changes. The critical missing link has been the connection between corollary discharge and visual processing. Here we show that such a link is formed by a corollary discharge from the thalamus that targets the frontal cortex. In the thalamus, neurons in the mediodorsal nucleus relay a corollary discharge of saccades from the midbrain superior colliculus to the cortical frontal eye field. In the frontal eye field, neurons use corollary discharge to shift their visual receptive fields spatially before saccades. We tested the hypothesis that these two components-a pathway for corollary discharge and neurons with shifting receptive fields-form a circuit in which the corollary discharge drives the shift. First we showed that the known spatial and temporal properties of the corollary discharge predict the dynamic changes in spatial visual processing of cortical neurons when saccades are made. Then we moved from this correlation to causation by isolating single cortical neurons and showing that their spatial visual processing is impaired when corollary discharge from the thalamus is interrupted. Thus the visual processing of frontal neurons is spatiotemporally matched with, and functionally dependent on, corollary discharge input from the thalamus. These experiments establish the first link between corollary discharge and visual processing, delineate a brain circuit that is well suited for mediating visual stability, and provide a framework for studying corollary discharge in other sensory systems.     

Topography of contextual modulations mediated by short-range interactions in primary visual cortex.

Neurons in primary visual cortex (V1) respond differently to a simple visual element presented in isolation from when it is embedded within a complex image. This difference, a specific modulation by surrounding elements in the image, is mediated by short- and long-range connections within V1 and by feedback from other areas. Here we study the role of short-range connections in this process, and relate it to the layout of local inhomogeneities in the cortical maps of orientation and space. By measuring correlation between neuron pairs located in optically imaged maps of V1 orientation columns we show that the strength of local connections between cells is a graded function of lateral separation across cortex, largely radially symmetrical and relatively independent of orientation preferences. We then show the contextual influence of flanking visual elements on neuronal responses varies systematically with a neuron's position within the cortical orientation map. The strength of this contextual influence on a neuron can be predicted from a model of local connections based on simple overlap with particular features of the orientation map. This indicates that local intracortical circuitry could endow neurons with a graded specialization for processing angular visual features such as corners and T junctions, and this specialization could have its own functional cortical map, linked with the orientation map.     

Selective cortical representation of attended speaker in multi-talker speech perception

Humans possess a remarkable ability to attend to a single speaker's voice in a multi-talker background. How the auditory system manages to extract intelligible speech under such acoustically complex and adverse listening conditions is not known, and, indeed, it is not clear how attended speech is internally represented. Here, using multi-electrode surface recordings from the cortex of subjects engaged in a listening task with two simultaneous speakers, we demonstrate that population responses in non-primary human auditory cortex encode critical features of attended speech: speech spectrograms reconstructed based on cortical responses to the mixture of speakers reveal the salient spectral and temporal features of the attended speaker, as if subjects were listening to that speaker alone. A simple classifier trained solely on examples of single speakers can decode both attended words and speaker identity. We find that task performance is well predicted by a rapid increase in attention-modulated neural selectivity across both single-electrode and population-level cortical responses. These findings demonstrate that the cortical representation of speech does not merely reflect the external acoustic environment, but instead gives rise to the perceptual aspects relevant for the listener's intended goal.     

Intrinsic functional architecture in the anaesthetized monkey brain

The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain's energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour. Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks. Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems (oculomotor, somatomotor and visual) and the 'default' system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness.     

Neuroscience: rewiring the adult brain

Any analysis of plastic reorganization at a neuronal locus needs a veridical measure of changes in the functional output--that is, spiking responses of the neurons in question. In a study of the effect of retinal lesions on adult primary visual cortex (V1), Smirnakis et al. propose that there is no cortical reorganization. Their results are based, however, on BOLD (blood-oxygen-level-dependent) fMRI (functional magnetic resonance imaging), which provides an unreliable gauge of spiking activity. We therefore question their criterion for lack of plasticity, particularly in the light of the large body of earlier work that demonstrates cortical plasticity.     

Disruption of cortical activity prevents ocular dominance changes in monocularly deprived kittens

Abundant evidence now indicates that atypical visual exposure early in the life of cats and primates can cause profound alterations in cortical organization. In particular, it has been shown that preventing the use of one eye for vision early in life results in a marked shift of ocular preference among neurones of kitten visual cortex in favour of the exposed eye. The cellular mechanisms underlying these alterations remain uncertain, but much recent attention has focused on the possible role of pharmacological agents in modifying cortical plasticity, with particular reference to catecholamines. These experiments, which have shown that agents which modify cortical noradrenaline levels can alter the degree of cortical plasticity, do not specify the mechanism of action, and leave open the possibility that other neurotransmitter systems may also be involved in cortical modifiability. We now report that chronic intracortical administration of L-glutamate during a period of monocular vision imposed on young kittens largely prevents the ocular dominance shift which normally occurs under these circumstances.     

Two methods of catecholamine depletion in kitten visual cortex yield different effects on plasticity

As first clearly demonstrated by the experiments of Wiesel and Hubel, the developing visual cortex is exquisitely sensitive to sensory deprivation. Temporary closure of one eye of a kitten during a critical period that extends from 3 weeks to 3 months of age results in a dramatic cortical reorganization such that most neurones, originally binocularly driven, are dominated exclusively by the open eye. Recently, attention has been directed to chemical factors which may influence the degree of plasticity during the critical period. The work of Kasamatsu and pettigrew suggests that cortical catecholamines, especially noradrenaline (NA), are essential for the normal plastic response to visual deprivation. In an effort to clarify the role of NA in visual cortical plasticity, we have monocularly deprived kittens whose cortex had been depleted of catecholamines by the neurotoxin 6-hydroxydopamine (6-OHDA). We used two strategies to deplete cortical NA: the first, pioneered by Kasamatsu el al., utilized osmotic minipumps to deliver 6-OHDA to visual cortex; the second involved systemic neonatal injections of 6-OHDA, a technique which has proved effective in rodents. We found, using high-pressure liquid chromatography (HPLC), that both techniques produced a substantial reduction in the level of cortical NA. However, single unit recording in area 17 revealed that the plastic response to monocular deprivation (MD) was only diminished in the kittens depleted by minipump.     

Potentiation of cortical inhibition by visual deprivation

The fine-tuning of circuits in sensory cortex requires sensory experience during an early critical period. Visual deprivation during the critical period has catastrophic effects on visual function, including loss of visual responsiveness to the deprived eye, reduced visual acuity, and loss of tuning to many stimulus characteristics. These changes occur faster than the remodelling of thalamocortical axons, but the intracortical plasticity mechanisms that underlie them are incompletely understood. Long-term depression of excitatory intracortical synapses has been proposed as a general candidate mechanism for the loss of cortical responsiveness after visual deprivation. Alternatively (or in addition), the decreased ability of the deprived eye to activate cortical neurons could be due to enhanced intracortical inhibition. Here we show that visual deprivation leaves excitatory connections in layer 4 (the primary input layer to cortex) unaffected, but markedly potentiates inhibitory feedback between fast-spiking basket cells (FS cells) and star pyramidal neurons (star pyramids). Further, a previously undescribed form of long-term potentiation of inhibition (LTPi) could be induced at synapses from FS cells to star pyramids, and was occluded by previous visual deprivation. These data suggest that potentiation of inhibition is a major cellular mechanism underlying the deprivation-induced degradation of visual function, and that this form of LTPi is important in fine-tuning cortical circuitry in response to visual experience.     

Selective deficit of visual search in moving displays after extrastriate damage

A visual cue that is often associated with significant stimuli, such as those provided by prey and predators, is movement relative to the observer. An efficient visual system should be able to direct attention to those parts of the visual field that contain such stimuli. What is needed is a system that can filter by movement difference. This could direct attention to a moving item among stationary items, or an item moving in one direction against a background moving in a different direction. Visual search experiments have shown that people are indeed able to filter by movement; that is, they can attend to just the moving items in arrays of moving and stationary stimuli. Single-cell recordings from monkey visual cortex show that the medial temporal cortical area (MT) has some of the properties required to filter by movement. We have now linked these two observations by showing that a patient with bilateral lesions to the presumed human homologue of MT cannot restrict visual attention to the moving items in arrays of both moving and stationary items. This suggests that MT is the site of a movement filter used in normal visual processing.