Cortical representation of space around the blind spot

The neural mechanism that mediates perceptual filling-in of the blind spot is still under discussion. One hypothesis proposes that the cortical representation of the blind spot is activated only under conditions that elicit perceptual filling-in and requires congruent stimulation on both sides of the blind spot. Alternatively, the passive remapping hypothesis proposes that inputs from regions surrounding the blind spot infiltrate the representation of the blind spot in cortex. This theory predicts that independent stimuli presented to the left and right of the blind spot should lead to neighboring/overlapping activations in visual cortex when the blind-spot eye is stimulated but separated activations when the fellow eye is stimulated. Using functional MRI, we directly tested the remapping hypothesis by presenting flickering checkerboard wedges to the left or right of the spatial location of the blind spot, either to the blind-spot eye or to the fellow eye. Irrespective of which eye was stimulated, we found separate activations corresponding to the left and right wedges. We identified the centroid of the activations on a cortical flat map and measured the distance between activations. Distance measures of the cortical gap across the blind spot were accurate and reliable (mean distance: 6-8 mm across subjects, SD approximately 1 mm within subjects). Contrary to the predictions of the remapping hypothesis, cortical distances between activations to the two wedges were equally large for the blind-spot eye and fellow eye in areas V1 and V2/V3. Remapping therefore appears unlikely to account for perceptual filling-in at an early cortical level.     

A computational model of perceptual fill-in following retinal degeneration

The ablation of afferent input results in the reorganization of sensory and motor cortices. In the primary visual cortex (V1), binocular retinal lesions deprive a corresponding cortical region [lesion projection zone (LPZ)] of visual input. Nevertheless, neurons in the LPZ regain responsiveness by shifting their receptive fields (RFs) outside the retinal lesions; this re-emergence of neural activity is paralleled by the perceptual completion of disrupted visual input in human subjects with retinal damage. To determine whether V1 reorganization can account for perceptual fill-in, we developed a neural network model that simulates the cortical remapping in V1. The model shows that RF shifts mediated by the plexus of spatial- and orientation-dependent horizontal connections in V1 can engender filling-in that is both robust and consistent with psychophysical reports of perceptual completion. Our model suggests that V1 reorganization may underlie perceptual fill-in, and it predicts spatial relationships between the original and remapped RFs that can be tested experimentally. More generally, it provides a general explanation for adaptive functional changes following CNS lesions, based on the recruitment of existing cortical connections that are involved in normal integrative mechanisms.     

Spatial updating in area LIP is independent of saccade direction

We explore the world around us by making rapid eye movements to objects of interest. Remarkably, these eye movements go unnoticed, and we perceive the world as stable. Spatial updating is one of the neural mechanisms that contributes to this perception of spatial constancy. Previous studies in macaque lateral intraparietal cortex (area LIP) have shown that individual neurons update, or "remap," the locations of salient visual stimuli at the time of an eye movement. The existence of remapping implies that neurons have access to visual information from regions far beyond the classically defined receptive field. We hypothesized that neurons have access to information located anywhere in the visual field. We tested this by recording the activity of LIP neurons while systematically varying the direction in which a stimulus location must be updated. Our primary finding is that individual neurons remap stimulus traces in multiple directions, indicating that LIP neurons have access to information throughout the visual field. At the population level, stimulus traces are updated in conjunction with all saccade directions, even when we consider direction as a function of receptive field location. These results show that spatial updating in LIP is effectively independent of saccade direction. Our findings support the hypothesis that the activity of LIP neurons contributes to the maintenance of spatial constancy throughout the visual field.     

Implications of ocular kinematics for the internal updating of visual space

Recent studies have suggested that during saccades cortical and subcortical representations of visual targets are represented and remapped in retinal coordinates. If this is correct, then the remapping processes must incorporate the noncommutativity of rotations. For example, our three-dimensional (3-D) simulations of the commutative vector-subtraction model of retinocentric remapping predicted centripetal errors in saccade trajectories between "remembered" eccentric targets, whereas our noncommutative model predicted accurate saccades. We tested between these two models in five head-fixed human subjects. Typically, a central fixation light appeared and two peripheral targets were flashed. With all targets extinguished, subjects were required to saccade to the remembered location of one of the peripheral targets and saccade between their remembered locations. Subjects showed minor misestimations of the spatial locations of targets, but failed to show the cumulative pattern of errors predicted by the commutative model. This experiment indicates that if targets are remapped in a retinal frame, then the remapping process also takes the noncommutativity of 3-D eye rotations into account. Unlike other noncommutative aspects of eye rotations that may have mechanical explanations, the noncommutative aspects of this process must be entirely internal.     

Neural correlates of sustained spatial attention in human early visual cortex

Attention is thought to enhance perceptual performance at attended locations through top-down attention signals that modulate activity in visual cortex. Here, we show that activity in early visual cortex is sustained during maintenance of attention in the absence of visual stimulation. We used functional magnetic resonance imaging (fMRI) to measure activity in visual cortex while human subjects performed a visual detection task in which a variable-duration delay period preceded target presentation. Portions of cortical areas V1, V2, and V3 representing the attended part of the visual field exhibited sustained increases in activity throughout the delay period. Portions of these cortical areas representing peripheral, unattended parts of the visual field displayed sustained decreases in activity. The data were well fit by a model that assumed the sustained neural activity was constant in amplitude over a time period equal to that of the actual delay period for each trial. These results demonstrate that sustained attention responses are present in early visual cortex (including primary visual cortex), in the absence of a visual stimulus, and that these responses correlate with the allocation of visuospatial attention in both the spatial and temporal domains.     

Retinotopic maps and foveal suppression in the visual cortex of amblyopic adults

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early–onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.     

Orientation-tuned FMRI adaptation in human visual cortex

Adaptation is a general property of almost all neural systems and has been a longstanding tool of psychophysics because of its power to isolate and temporarily reduce the contribution of specific neural populations. Recently, adaptation designs have been extensively applied in functional MRI (fMRI) studies to infer neural selectivity in specific cortical areas. However, there has been considerable variability in the duration of adaptation used in these experiments. In particular, although long-term adaptation has been solidly established in psychophysical and neurophysiological studies, it has been incorporated into few fMRI studies. Furthermore, there has been little validation of fMRI adaptation using stimulus dimensions with well-known adaptive properties (e.g., orientation) and in better understood regions of cortex (e.g., primary visual cortex, V1). We used an event-related fMRI experiment to study long-term orientation adaptation in the human visual cortex. After long-term adaptation to an oriented pattern, the fMRI response in V1, V2, V3/VP, V3A, and V4 to a test stimulus was proportional to the angular difference between the adapting and test stimuli. However, only V3A and V4 showed this response pattern with short-term adaptation. In a separate experiment, we measured behavioral contrast detection thresholds after adaptation and found that the fMRI signal in V1 closely matched the psychophysically derived contrast detection thresholds. Similar to the fMRI results, adaptation induced threshold changes strongly depended on the duration of adaptation. In addition to supporting the existence of adaptable orientation-tuned neurons in human visual cortex, our results show the importance of considering timing parameters in fMRI adaptation experiments.     

Modulation of sensory suppression: implications for receptive field sizes in the human visual cortex

Neurophysiological studies in monkeys show that when multiple visual stimuli appear simultaneously in the visual field, they are not processed independently, but rather interact in a mutually suppressive way. This suggests that multiple stimuli compete for neural representation. Consistent with this notion, we have previously found in humans that functional magnetic resonance imaging (fMRI) signals in V1 and ventral extrastriate areas V2, V4, and TEO are smaller for simultaneously presented (i.e., competing) stimuli than for the same stimuli presented sequentially (i.e., not competing). Here we report that suppressive interactions between stimuli are also present in dorsal extrastriate areas V3A and MT, and we compare these interactions to those in areas V1 through TEO. To exclude the possibility that the differences in responses to simultaneously and sequentially presented stimuli were due to differences in the number of transient onsets, we tested for suppressive interactions in area V4, in an experiment that held constant the number of transient onsets. We found that the fMRI response to a stimulus in the upper visual field was suppressed by the presence of nearby stimuli in the lower visual field. Further, we excluded the possibility that the greater fMRI responses to sequential compared with simultaneous presentations were due to exogeneous attentional cueing by having our subjects count T's or L's at fixation, an attentionally demanding task. Behavioral testing demonstrated that neither condition interfered with performance of the T/L task. Our previous findings suggested that suppressive interactions among nearby stimuli in areas V1 through TEO were scaled to the receptive field (RF) sizes of neurons in those areas. Here we tested this idea by parametrically varying the spatial separation among stimuli in the display. Display sizes ranged from 2 x 2 degrees to 7 x 7 degrees and were centered at 5.5 degrees eccentricity. Based on the effects of display size on the magnitude of suppressive interactions, we estimated that RF sizes at an eccentricity of 5.5 degrees were <2 degrees in V1, 2-4 degrees in V2, 4-6 degrees in V4, larger than 7 degrees (but still confined to a quadrant) in TEO, and larger than 6 degrees (confined to a quadrant) in V3A. These estimates of RF sizes in human visual cortex are strikingly similar to those measured in physiological mapping studies in the homologous visual areas in monkeys.     

Spatially specific FMRI repetition effects in human visual cortex

The functional MRI (fMRI) response to a pair of identical, successively presented stimuli can result in a smaller signal than the presentation of two nonidentical stimuli. This "repetition effect" has become a frequently used tool to make inferences about neural selectivity in specific cortical areas. However, little is known about the mechanism(s) underlying the effect. In particular, despite many successful applications of the technique in higher visual areas, repetition effects in lower visual areas [e.g., primary visual cortex (V1)] have been more difficult to characterize. One property that is well understood in early visual areas is the mapping of visual field locations to specific areas of the cortex (i.e., retinotopy). We used the retinotopic organization of V1 to activate progressively different populations of neurons in a rapid fMRI experimental design. We observed a repetition effect (reduced signal) when localized stimulus elements were repeated in identical locations. We show that this effect is spatially tuned and largely independent of both interstimulus interval (100-800 ms) and the focus of attention. Using the same timing parameters for which we observed a large effect of spatial position, we also examined the response to orientation changes and observed no effect of an orientation change on the response to repeated stimuli in V1 but significant effects in other retinotopic areas. Given these results, we discuss the possible causes of these repetition effects as well as the implications for interpreting other experiments that use this potentially powerful imaging technique.     

Adaptive changes in early and late blind: a FMRI study of verb generation to heard nouns

Literacy for blind people requires learning Braille. Along with others, we have shown that reading Braille activates visual cortex. This includes striate cortex (V1), i.e., banks of calcarine sulcus, and several higher visual areas in lingual, fusiform, cuneus, lateral occipital, inferior temporal, and middle temporal gyri. The spatial extent and magnitude of magnetic resonance (MR) signals in visual cortex is greatest for those who became blind early in life. Individuals who lost sight as adults, and subsequently learned Braille, still exhibited activity in some of the same visual cortex regions, especially V1. These findings suggest these visual cortex regions become adapted to processing tactile information and that this cross-modal neural change might support Braille literacy. Here we tested the alternative hypothesis that these regions directly respond to linguistic aspects of a task. Accordingly, language task performance by blind persons should activate the same visual cortex regions regardless of input modality. Specifically, visual cortex activity in blind people ought to arise during a language task involving heard words. Eight early blind, six late blind, and eight sighted subjects were studied using functional magnetic resonance imaging (fMRI) during covert generation of verbs to heard nouns. The control task was passive listening to indecipherable sounds (reverse words) matched to the nouns in sound intensity, duration, and spectral content. Functional responses were analyzed at the level of individual subjects using methods based on the general linear model and at the group level, using voxel based ANOVA and t-test analyses. Blind and sighted subjects showed comparable activation of language areas in left inferior frontal, dorsolateral prefrontal, and left posterior superior temporal gyri. The main distinction was bilateral, left dominant activation of the same visual cortex regions previously noted with Braille reading in all blind subjects. The spatial extent and magnitude of responses was greatest on the left in early blind individuals. Responses in the late blind group mostly were confined to V1 and nearby portions of the lingual and fusiform gyri. These results confirm the presence of adaptations in visual cortex of blind people but argue against the notion that this activity during Braille reading represents somatosensory (haptic) processing. Rather, we suggest that these responses can be most parsimoniously explained in terms of linguistic operations. It remains possible that these responses represent adaptations which initially are for processing either sound or touch, but which are later generalized to the other modality during acquisition of Braille reading skills.     

Large-scale remapping of visual cortex is absent in adult humans with macular degeneration

The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively.     

Sparse coding in striate and extrastriate visual cortex

Theoretical studies of mammalian cortex argue that efficient neural codes should be sparse. However, theoretical and experimental studies have used different definitions of the term "sparse" leading to three assumptions about the nature of sparse codes. First, codes that have high lifetime sparseness require few action potentials. Second, lifetime-sparse codes are also population-sparse. Third, neural codes are optimized to maximize lifetime sparseness. Here, we examine these assumptions in detail and test their validity in primate visual cortex. We show that lifetime and population sparseness are not necessarily correlated and that a code may have high lifetime sparseness regardless of how many action potentials it uses. We measure lifetime sparseness during presentation of natural images in three areas of macaque visual cortex, V1, V2, and V4. We find that lifetime sparseness does not increase across the visual hierarchy. This suggests that the neural code is not simply optimized to maximize lifetime sparseness. We also find that firing rates during a challenging visual task are higher than theoretical values based on metabolic limits and that responses in V1, V2, and V4 are well-described by exponential distributions. These findings are consistent with the hypothesis that neurons are optimized to maximize information transmission subject to metabolic constraints on mean firing rate.     

The background is remapped across saccades

Physiological studies have found that neurons prepare for impending eye movements, showing anticipatory responses to stimuli presented at the location of the post-saccadic receptive fields (RFs) (Wurtz in Vis Res 48:2070–2089, 2008). These studies proposed that visual neurons with shifting RFs prepared for the stimuli they would process after an impending saccade. Additionally, psychophysical studies have shown behavioral consequences of those anticipatory responses, including the transfer of aftereffects (Melcher in Nat Neurosci 10:903–907, 2007) and the remapping of attention (Rolfs et al. in Nat Neurosci 14:252–258, 2011). As the physiological studies proposed, the shifting RF mechanism explains the transfer of aftereffects. Recently, a new mechanism based on activation transfer via a saliency map was proposed, which accounted for the remapping of attention (Cavanagh et al. in Trends Cogn Sci 14:147–153, 2010). We hypothesized that there would be different aspects of the remapping corresponding to these different neural mechanisms. This study found that the information in the background was remapped to a similar extent as the figure, provided that the visual context remained stable. We manipulated the status of the figure and the ground in the saliency map and showed that the manipulation modulated the remapping of the figure and the ground in different ways. These results suggest that the visual system has an ability to remap the background as well as the figure, but lacks the ability to modulate the remapping of the background based on the visual context, and that different neural mechanisms might work together to maintain visual stability across saccades.     

Impact of coordinate transformation uncertainty on human sensorimotor control

Humans build representations of objects and their locations by integrating imperfect information from multiple perceptual modalities (e.g., visual, haptic). Because sensory information is specified in different frames of reference (i.e., eye- and body-centered), it must be remapped into a common coordinate frame before integration and storage in memory. Such transformations require an understanding of body articulation, which is estimated through noisy sensory data. Consequently, target information acquires additional coordinate transformation uncertainty (CTU) during remapping because of errors in joint angle sensing. As a result, CTU creates differences in the reliability of target information depending on the reference frame used for storage. This paper explores whether the brain represents and compensates for CTU when making grasping movements. To address this question, we varied eye position in the head, while participants reached to grasp a spatially fixed object, both when the object was in view and when it was occluded. Varying eye position changes CTU between eye and head, producing additional uncertainty in remapped information away from forward view. The results showed that people adjust their maximum grip aperture to compensate both for changes in visual information and for changes in CTU when the target is occluded. Moreover, the amount of compensation is predicted by a Bayesian model for location inference that uses eye-centered storage.     

BDNF upregulation during declarative memory formation in monkey inferior temporal cortex

In primates, visual long-term memory of objects is presumably stored in the inferior temporal (IT) cortex. Because brain-derived neurotrophic factor (BDNF) is involved in activity-dependent neural reorganization, we tested the hypothesis that BDNF would be upregulated in IT cortex during formation of visual pair-association memory. To eliminate genetic and cognitive variations between individual animals, we used split-brain monkeys for intra-animal comparison in PCR-based mRNA quantitation. The monkeys learned a pair-association (PA) task using one hemisphere and a control visual task using the other, to balance the amount of visual input. We found that BDNF was upregulated selectively in area 36 of IT cortex during PA learning, but not in areas involved in earlier stages of visual processing. In situ hybridization showed that BDNF-expressing cells were localized in a patchlike cluster. The results suggest that BDNF contributes to reorganization of neural circuits for visual long-term memory formation in the primate.     

Eye dominance predicts fMRI signals in human retinotopic cortex

There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a 'hole in hand' variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4v, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4v). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures.     

Task-related modulation of visual cortex

We performed a series of experiments to quantify the effects of task performance on cortical activity in early visual areas. Functional magnetic resonance imaging (fMRI) was used to measure cortical activity in several cortical visual areas including primary visual cortex (V1) and the MT complex (MT+) as subjects performed a variety of threshold-level visual psychophysical tasks. Performing speed, direction, and contrast discrimination tasks produced strong modulations of cortical activity. For example, one experiment tested for selective modulations of MT+ activity as subjects alternated between performing contrast and speed discrimination tasks. MT+ responses modulated in phase with the periods of time during which subjects performed the speed discrimination task; that is, MT+ activity was higher during speed discrimination than during contrast discrimination. Task-related modulations were consistent across repeated measurements in each subject; however, significant individual differences were observed between subjects. Together, the results suggest 1) that specific changes in the cognitive/behavioral state of a subject can exert selective and reliable modulations of cortical activity in early visual cortex, even in V1; 2) that there are significant individual differences in these modulations; and 3) that visual areas and pathways that are highly sensitive to small changes in a given stimulus feature (such as contrast or speed) are selectively modulated during discrimination judgments on that feature. Increasing the gain of the relevant neuronal signals in this way may improve their signal-to-noise to help optimize task performance.     

Effect of eye movements on the magnitude of functional magnetic resonance imaging responses in extrastriate cortex during visual motion perception

We have studied the effects of pursuit eye movements on the functional magnetic resonance imaging (fMRI) responses in extrastriate visual areas during visual motion perception. Echoplanar imaging of 10–12 image planes through visual cortex was acquired in nine subjects while they viewed sequences of random-dot motion. Images obtained during stimulation periods were compared with baseline images, where subjects viewed a blank field. In a subsidiary experiment, responses to moving dots, viewed under conditions of fixation or pursuit, were compared with those evoked by static dots. Eye movements were recorded with MR-compatible electro-oculographic (EOG) electrodes. Our findings show an enhanced level of activation (as indexed by blood-oxygen level-dependent contrast) during pursuit compared with fixation in two extrastriate areas. The results support earlier findings on a motion-specific area in lateral occipitotemporal cortex (human V5). They also point to a further site of activation in a region approximately 12 mm dorsal of V5. The fMRI response in V5 during pursuit is significantly enhanced. This increased response may represent additional processing demands required for the control of eye movements. Received: 16 July 1997 / Accepted: 14 October 1997     

Gaze and smooth pursuit signals interact in parietal area 7m of the behaving monkey

Posterior parietal cortex is a region specialized for multimodal integration and coordinate transformations which converts sensory input to motor output. Eye position signals are crucial for such transformations, because they are needed to the inner reconstruction of a stable image of the outside world in spite of eye movements. Area 7m is a parietal area anatomically connected with oculomotor structures such as frontal eye field and superior colliculus. The aim of this study was to assess if neurons in area 7m possess activity related to eye movements, and if so, which sort of movements are processed. We recorded the extracellular activity of 7m neurons in two monkeys trained in both a smooth pursuit and a visually guided saccade task. The majority of neurons tested with the smooth pursuit task (16/17) showed directional selectivity influenced by the eye position. Moreover, these neurons were tuned to inward or outward pursuit with respect to the center of extra-personal visual space. About half of the cells (11/24) tested with the saccade task changed their activity during the pre-saccadic period. The majority of neurons presented post-saccadic activity: most of the cells showed a directionally-selective phasic response and a modulation by eye position during fixation (23/24). Overall, we observed that area 7m contains a population of neurons signaling smooth pursuit direction at certain eye position and saccade direction toward specific portions of the visual space. We hypothesize that area 7m might be involved in spatial map updating which can be used for spatial orientation. Supported by the Italian Ministry for University and Scientific Research (MURST).     

Involvement of striate and extrastriate visual cortical areas in spatial attention

We investigated the cortical mechanisms of visual-spatial attention while subjects discriminated patterned targets within distractor arrays. Functional magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic visual areas and to localize attention-related changes in neural activity within several of those areas, including primary visual (striate) cortex. Event-related potentials (ERPs) and modeling of their neural sources, however, indicated that the initial sensory input to striate cortex at 50-55 milliseconds after the stimulus was not modulated by attention. The earliest facilitation of attended signals was observed in extrastriate visual areas, at 70-75 milliseconds. We hypothesize that the striate cortex modulation found with fMRI may represent a delayed, re-entrant feedback from higher visual areas or a sustained biasing of striate cortical neurons during attention. ERP recordings provide critical temporal information for analyzing the functional neuroanatomy of visual attention.