Ignition's glow: Ultra-fast spread of global cortical activity accompanying local "ignitions" in visual cortex during conscious visual perception.

Despite extensive research, the spatiotemporal span of neuronal activations associated with the emergence of a conscious percept is still debated. The debate can be formulated in the context of local vs. global models, emphasizing local activity in visual cortex vs. a global fronto-parietal "workspace" as the key mechanisms of conscious visual perception. These alternative models lead to differential predictions with regard to the precise magnitude, timing and anatomical spread of neuronal activity during conscious perception. Here we aimed to test a specific aspect of these predictions in which local and global models appear to differ - namely the extent to which fronto-parietal regions modulate their activity during task performance under similar perceptual states. So far the main experimental results relevant to this debate have been obtained from non-invasive methods and led to conflicting interpretations. Here we examined these alternative predictions through large-scale intracranial measurements (Electrocorticogram - ECoG) in 43 patients and 4445 recording sites. Both ERP and broadband high frequency (50-150 Hz - BHF) responses were examined through the entire cortex during a simple 1-back visual recognition memory task. Our results reveal short latency intense visual responses, localized first in early visual cortex followed (at ∼200 ms) by higher order visual areas, but failed to show significant delayed (300 ms) visual activations. By contrast, oddball image repeat events, linked to overt motor responses, were associated with a significant increase in a delayed (300 ms) peak of BHF power in fronto-parietal cortex. Comparing BHF responses with ERP revealed an additional peak in the ERP response - having a similar latency to the well-studied P3 scalp EEG response. Posterior and temporal regions demonstrated robust visual category selectivity. An unexpected observation was that high-order visual cortex responses were essentially concurrent (at ∼200 ms) with an ultra-fast spread of signals of lower magnitude that invaded selected sites throughout fronto-parietal cortical areas. Our results are compatible with local models in demonstrating a clear task-dependence of the 300 ms fronto-parietal activation. However, they also reveal a more global component of low-magnitude and poor content selectivity that rapidly spreads into fronto-parietal sites. The precise functional role of this global "glow" remains to be elucidated.

Human single-neuron responses at the threshold of conscious recognition.

We studied the responses of single neurons in the human medial temporal lobe while subjects viewed familiar faces, animals, and landmarks. By progressively shortening the duration of stimulus presentation, coupled with backward masking, we show two striking properties of these neurons. (i) Their responses are not statistically different for the 33-ms, 66-ms, and 132-ms stimulus durations, and only for the 264-ms presentations there is a significantly higher firing. (ii) These responses follow conscious perception, as indicated by the subjects' recognition report. Remarkably, when recognized, a single snapshot as brief as 33 ms was sufficient to trigger strong single-unit responses far outlasting stimulus presentation. These results suggest that neurons in the medial temporal lobe can reflect conscious recognition by "all-or-none" responses.

Ultra-fine frequency tuning revealed in single neurons of human auditory cortex.

Just-noticeable differences of physical parameters are often limited by the resolution of the peripheral sensory apparatus. Thus, two-point discrimination in vision is limited by the size of individual photoreceptors. Frequency selectivity is a basic property of neurons in the mammalian auditory pathway. However, just-noticeable differences of frequency are substantially smaller than the bandwidth of the peripheral sensors. Here we report that frequency tuning in single neurons recorded from human auditory cortex in response to random-chord stimuli is far narrower than that typically described in any other mammalian species (besides bats), and substantially exceeds that attributed to the human auditory periphery. Interestingly, simple spectral filter models failed to predict the neuronal responses to natural stimuli, including speech and music. Thus, natural sounds engage additional processing mechanisms beyond the exquisite frequency tuning probed by the random-chord stimuli.

Selective fovea-related deprived activation in retinotopic and high-order visual cortex of human amblyopes.

Amblyopia is a visual disorder starting at early childhood and characterized by reduced visual acuity not of optical origin or due to any eye disease. One expression of such an anomalous early visual experience is abnormal foveal vision. In a previous fMRI study, faces that were presented to amblyopic eyes evoked little response compared to houses in high-order visual areas. Patients also demonstrated reduced recognition of facial expression, raising the possibility that these face-selective abnormalities are related to foveal vision deficit. Whether this deficit originates in low-level processing or is mediated by compromised activation in high-order visual areas is unresolved. In the present functional magnetic resonance imaging (fMRI) study, we explored the impact of amblyopia on the representation of object images presented in foveally biased central versus peripheral retinotopic eccentricities through manipulation of object size. Small and large pictures were correlated to visual acuities of 6/6 and 6/60, respectively. In low-level visual areas, the amblyopic eye showed significantly reduced activation for centrally placed, small pictures than the sound eye, while activation to large pictures was only slightly reduced. Similarly, in high-order visual areas, the amblyopic eye showed marked reduction in activation in the fusiform gyrus, with normal activation in the collateral sulcus. The center/periphery size-related amblyopic outcomes of this study support a "bottom-up" nature of the center-periphery effect observed in high-order visual areas. Taken together, these findings point to the regional extent and functional selectivity of fovea-related cortical reorganization that is related to abnormal visual development of one eye.

Area-specific amblyopic effects in human occipitotemporal object representations.

The role of early visual experience in the establishment of human high-order visual areas is poorly understood. Here we investigated this issue using human amblyopia--a developmental visual disorder, which manifests a central vision (acuity) deficit. Previous fMRI studies of amblyopes have described abnormal functional activations in early retinotopic areas. Here we report the surprising finding of a selective object-related abnormality in high-order occipitotemporal cortex. Specifically, we found that face-related cortical areas show a severe disconnection from the amblyopic eye, while building-related regions remain essentially normal. The selectivity of the deficit highlights the differential computations performed in the different object-related areas and is compatible with the suggested association of face regions with analysis of fine detail.

Object-completion effects in the human lateral occipital complex.

The ability of the human visual system to recognize partially occluded objects is a striking feat, which has received extensive psychophysical documentation. Here we studied the manifestation of completion effects in the functional magnetic resonance imaging (fMRI) activation of high-order object areas (the lateral occipital complex - LOC). Subjects were presented with three types of images: (i) whole line drawings of animal or unfamiliar shapes ('whole'); (ii) the same shapes, occluded by parallel stripes which occupied roughly half of the surface area of the images ('grid'); and (iii) the same stripes, 'scrambled' so that the relative position of the regions between the stripes was changed while the local feature structure remained intact. Behavioral measurements showed a high degree of object completion in the 'grid' condition, but not in the 'scrambled' condition. The fMRI results show a significantly higher activation to the 'grid' images compared to the 'scrambled' images. This enhanced activation indicates the operation of non-local completion effects, since the local features in both sets of images were the same. The cortical regions showing the highest 'completion' effects co-localized with regions in the LOC which showed the highest activation to the 'whole' images compared to the 'scrambled' images. Activation in early retinotopic areas was similar in both the 'grid' and the 'scrambled' conditions. Our results point to the LOC as a central site in which object completion effects are manifested.

Feeling or features: different sensitivity to emotion in high-order visual cortex and amygdala.

Emotionally loaded visual stimuli have shown increased activation in visual and cortex limbic areas. However, differences in visual features of such images could confound these findings. In order to manipulate valence of stimuli while keeping visual features largely unchanged, we took advantage of an "expressional transfiguration" (ET) effect of faces. In addition, we used repetition effects, which enabled us to test more incisively the impact of the ET effect. Using the ET manipulation, we have shown that the activation in lateral occipital complex (LOC) was unaffected by valence attributes, but produced significant modulation of fMR adaptation. Contrary to LOC, amygdala activation was increased by ET manipulation unrelated to the adaptation. A correlation between amygdala and LOC adaptation points to a possible modulatory role of the amygdala upon visual cortex short-term plasticity.

Vase or face? A neural correlate of shape-selective grouping processes in the human brain.

Recent neuroimaging studies have described a differential activation pattern associated with specific object images (e.g., face-related and building-related activation) in human occipito-temporal cortex. However, it is as yet unclear to what extent this selectivity is due to differences in the statistics of local object features present in the different object categories, and to what extent it reflects holistic grouping processes operating across the entire object image. To resolve this question it is essential to use images in which identical sets of local features elicit the perception of different object categories. The classic Rubin vase-face illusion provides an excellent experimental set to test this question. In the illusion, the same local contours lead to the perception of different objects (vase or face). Here we employed a modified Rubin vase-face illusion to explore to what extent the activation in face-related regions is attributable to the presence of local face features, or is due to a more holistic grouping process that involves the entire face figure. Biasing cues (gratings and color) were used to control the perceptual state of the observer. We found enhanced activation in face-related regions during the "face profile" perceptual state compared to the "vase" perceptual state. Control images ruled out the involvement of the biasing cues in the effect. Thus, object-selective activation in human face-related regions entails global grouping processes that go beyond the local processing of stimulus features.

fMR-adaptation: a tool for studying the functional properties of human cortical neurons.

The invariant properties of human cortical neurons cannot be studied directly by fMRI due to its limited spatial resolution. One voxel obtained from a fMRI scan contains several hundred thousands neurons. Therefore, the fMRI signal may average out a heterogeneous group of highly selective neurons. Here, we present a novel experimental paradigm for fMRI, functional magnetic resonance-adaptation (fMR-A), that enables to tag specific neuronal populations within an area and investigate their functional properties. This approach contrasts with conventional mapping methods that measure the averaged activity of a region. The application of fMR-A to study the functional properties of cortical neurons proceeds in two stages: First, the neuronal population is adapted by repeated presentation of a single stimulus. Second, some property of the stimulus is varied and the recovery from adaptation is assessed. If the signal remains adapted, it will indicate that the neurons are invariant to that attribute. However, if the fMRI signal will recover from the adapted state it would imply that the neurons are sensitive to the property that was varied. Here, an application of fMR-A for studying the invariant properties of high-order object areas (lateral occipital complex--LOC) to changes in object size, position, illumination and rotation is presented. The results show that LOC is less sensitive to changes in object size and position compared to changes of illumination and viewpoint. fMR-A can be extended to other neuronal systems in which adaptation is manifested and can be used with event-related paradigms as well. By manipulating experimental parameters and testing recovery from adaptation it should be possible to gain insight into the functional properties of cortical neurons which are beyond the spatial resolution limits imposed by conventional fMRI.

Center-periphery organization of human object areas.

The organizing principles that govern the layout of human object-related areas are largely unknown. Here we propose a new organizing principle in which object representations are arranged according to a central versus peripheral visual field bias. The proposal is based on the finding that building-related regions overlap periphery-biased visual field representations, whereas face-related regions are associated with center-biased representations. Furthermore, the eccentricity maps encompass essentially the entire extent of object-related occipito-temporal cortex, indicating that most object representations are organized with respect to retinal eccentricity. A control experiment ruled out the possibility that the results are due exclusively to unequal feature distribution in these images. We hypothesize that brain regions representing object categories that rely on detailed central scrutiny (such as faces) are more strongly associated with processing of central information, compared to representations of objects that may be recognized by more peripheral information (such as buildings or scenes).

A hierarchical axis of object processing stages in the human visual cortex.

How are objects represented in the human visual cortex? Two conflicting theories suggest either a holistic representation, in which objects are represented by a collection of object templates, or a part-based representation, in which objects are represented as collections of features or object parts. We studied this question using a gradual object-scrambling paradigm in which pictures of objects (faces and cars) were broken in a stepwise manner into an increasing number of blocks. Our results reveal a hierarchical axis oriented anterior--posteriorly in the organization of ventral object-areas. Along this axis, representations are arranged in bands of increasing sensitivity to image scrambling. The axis starts in early visual areas through retinotopic areas V4/V8 and continues into the lateral-occipital sulcus dorsally and the posterior fusiform girus ventrally, corresponding together to the previously described object-related lateral occipital complex (LOC). Regions showing the highest sensitivity to scrambling tended to be located at the most anterior-lateral regions of the complex. In these more anterior regions, breaking the images into 16 parts produced a significant reduction in activation. Interestingly, activation was not affected when images were cut in two halves, either horizontally or vertically. Car images generally produced a weaker activation compared to faces in the lateral occipital complex but showed the same tendency of increased scrambling sensitivity along the anterior--posterior axis. These results suggest the existence of a hierarchical axis along ventral occipito-temporal object-areas, in which the neuronal properties shift from sensitivity to local object features to a more global and holistic representation.

Visuo-haptic object-related activation in the ventral visual pathway.

The ventral pathway is involved in primate visual object recognition. In humans, a central stage in this pathway is an occipito-temporal region termed the lateral occipital complex (LOC), which is preferentially activated by visual objects compared to scrambled images or textures. However, objects have characteristic attributes (such as three-dimensional shape) that can be perceived both visually and haptically. Therefore, object-related brain areas may hold a representation of objects in both modalities. Using fMRI to map object-related brain regions, we found robust and consistent somatosensory activation in the occipito-temporal cortex. This region showed clear preference for objects compared to textures in both modalities. Most somatosensory object-selective voxels overlapped a part of the visual object-related region LOC. Thus, we suggest that neuronal populations in the occipito-temporal cortex may constitute a multimodal object-related network.

The dynamics of object-selective activation correlate with recognition performance in humans.

To investigate the relationship between perceptual awareness and brain activity, we measured both recognition performance and fMRI signal from object-related areas in human cortex while images were presented briefly using a masking protocol. Our results suggest that recognition performance is correlated with selective activation in object areas. Selective activation was correlated to object naming when exposure duration was varied from 20 to 500 milliseconds. Subjects' recognition during identical visual stimulation could be enhanced by training, which also increased the fMRI signal. Overall, the correlation between recognition performance and fMRI signal was highest in occipitotemporal object areas (the lateral occipital complex).

Differential processing of objects under various viewing conditions in the human lateral occipital complex.

The invariant properties of human cortical neurons cannot be studied directly by fMRI due to its limited spatial resolution. Here, we circumvented this limitation by using fMR adaptation, namely, reduction of the fMR signal due to repeated presentation of identical images. Object-selective regions (lateral occipital complex [LOC]) showed a monotonic signal decrease as repetition frequency increased. The invariant properties of fMR adaptation were studied by presenting the same object in different viewing conditions. LOC exhibited stronger fMR adaptation to changes in size and position (more invariance) compared to illumination and viewpoint. The effect revealed two putative subdivisions within LOC: caudal-dorsal (LO), which exhibited substantial recovery from adaptation under all transformations, and posterior fusiform (PF/LOa), which displayed stronger adaptation. This study demonstrates the utility of fMR adaptation for revealing functional characteristics of neurons in fMRI studies.

Cue-invariant activation in object-related areas of the human occipital lobe.

The extent to which primary visual cues such as motion or luminance are segregated in different cortical areas is a subject of controversy. To address this issue, we examined cortical activation in the human occipital lobe using functional magnetic resonance imaging (fMRI) while subjects performed a fixed visual task, object recognition, using three different primary visual cues: motion, texture, or luminance contrast. In the first experiment, a region located on the lateral aspect of the occipital lobe (LO complex) was preferentially activated in all 11 subjects both by luminance and motion-defined object silhouettes compared to full-field moving and stationary noise (ratios, 2.00+/-0.19 and 1.86+/-0.65, respectively). In the second experiment, all subjects showed enhanced activation in the LO complex to objects defined both by luminance and texture contrast compared to full-field texture patterns (ratios, 1.43+/-0.08 and 1.32+/-0.08, respectively). An additional smaller dorsal focus that exhibited convergence of object-related cues appeared to correspond to area V3a or a region slightly anterior to it. These results show convergence of visual cues in LO and provide strong evidence for its role in object processing.

A sequence of object-processing stages revealed by fMRI in the human occipital lobe.

Functional magnetic resonance imaging was used in combined functional selectivity and retinotopic mapping tests to reveal object-related visual areas in the human occipital lobe. Subjects were tested with right, left, up, or down hemivisual field stimuli which were composed of images of natural objects (faces, animals, man-made objects) or highly scrambled (1,024 elements) versions of the same images. In a similar fashion, the horizontal and vertical meridians were mapped to define the borders of these areas. Concurrently, the same cortical sites were tested for their sensitivity to image-scrambling by varying the number of scrambled picture fragments (from 16-1,024) while controlling for the Fourier power spectrum of the pictures and their order of presentation. Our results reveal a stagewise decrease in retinotopy and an increase in sensitivity to image-scrambling. Three main distinct foci were found in the human visual object recognition pathway (Ungerleider and Haxby [1994]: Curr Opin Neurobiol 4:157-165): 1) Retinotopic primary areas V1-3 did not exhibit significant reduction in activation to scrambled images. 2) Areas V4v (Sereno et al., [1995]: Science 268:889-893) and V3A (De Yoe et al., [1996]: Proc Natl Acad Sci USA 93:2382-2386; Tootell et al., [1997]: J Neurosci 71:7060-7078) manifested both retinotopy and decreased activation to highly scrambled images. 3) The essentially nonretinotopic lateral occipital complex (LO) (Malach et al., [1995]: Proc Natl Acad Sci USA 92:8135-8139; Tootell et al., [1996]: Trends Neurosci 19:481-489) exhibited the highest sensitivity to image scrambling, and appears to be homologous to macaque the infero-temporal (IT) cortex (Tanaka [1996]: Curr Opin Neurobiol 523-529). Breaking the images into 64, 256, or 1,024 randomly scrambled blocks reduced activation in LO voxels. However, many LO voxels remained significantly activated by mildly scrambled images (16 blocks). These results suggest the existence of object-fragment representation in LO.

Organization of intrinsic connections in owl monkey area MT.

Area MT (middle temporal) is a well-defined visual representation common to all primates, which shows a clear selectivity to the analysis of visual motion. In the present study we examined the architecture of the intrinsic connections in area MT in an attempt to reveal its organizing principles and its potential relationship to the functional domains in area MT. Intrinsic connections were studied by placing small injections of the tracer biocytin in area MT of seven adult owl monkeys (Aotus nancymae). The injections were targeted at well-defined orientation domains revealed using optical imaging of intrinsic signals. The distribution of axons labeled by these injections was related both to the cytochrome oxidase histochemistry and to the layout of functional domains in area MT and surrounding tissue. Tracer injections in the superficial layers of area MT produced a complex network of extrinsic and intrinsic axonal connections. Clear instances of extrinsic connections were observed between area MT proper and the MT crescent situated postero-medially to it. The intrinsic connections were laterally spread and organized in patch-like clusters with an average distance from injection center to the furthest patch of 1.8 +/- 0.55 mm (+/-SD, n = 9). The overall axonal distribution tended to be anisotropic, i.e. the patches were distributed within an elongated ellipse [average anisotropy ratio: 1.86 +/- 0.66 (+/-SD)] and were asymmetrically distributed about either side of the injection site [average asymmetry ratio: 2.3 +/- 0.7 (+/-SD)]. Finally, there was a tendency for the intrinsic connections to connect to functional domains of similar orientation preference in area MT. However, this tendency varied substantially between individual cases. The highly specific nature of MT lateral connections puts clear constraints on models of surround influences in the receptive fields of MT neurons.

New images from human visual cortex.

Recent developments in imaging and histology have greatly clarified our understanding of the nature and organization of human visual cortex. More than ten human cortical visual areas can now be differentiated, compared with the approximately 30 areas described in macaque monkeys. Most human areas and columns described so far appear quite similar to those in macaque but distinctive species differences also exist. Imaging studies suggest two general information-processing streams (parietal and temporal) in human visual cortex, as proposed in macaque. Several human areas are both motion- and direction-selective, and a progression of motion-processing steps can be-inferred from the imaging data. Human visual areas for recognizing form are less well defined but the evidence again suggests a progression of information-processing steps and areas, beginning posterior to the human middle temporal area (or V5), and extending inferiorly then anteriorly. This is consistent with findings from macaque, and with human clinical reports.

Object-related activity revealed by functional magnetic resonance imaging in human occipital cortex.

The stages of integration leading from local feature analysis to object recognition were explored in human visual cortex by using the technique of functional magnetic resonance imaging. Here we report evidence for object-related activation. Such activation was located at the lateral-posterior aspect of the occipital lobe, just abutting the posterior aspect of the motion-sensitive area MT/V5, in a region termed the lateral occipital complex (LO). LO showed preferential activation to images of objects, compared to a wide range of texture patterns. This activation was not caused by a global difference in the Fourier spatial frequency content of objects versus texture images, since object images produced enhanced LO activation compared to textures matched in power spectra but randomized in phase. The preferential activation to objects also could not be explained by different patterns of eye movements: similar levels of activation were observed when subjects fixated on the objects and when they scanned the objects with their eyes. Additional manipulations such as spatial frequency filtering and a 4-fold change in visual size did not affect LO activation. These results suggest that the enhanced responses to objects were not a manifestation of low-level visual processing. A striking demonstration that activity in LO is uniquely correlated to object detectability was produced by the "Lincoln" illusion, in which blurring of objects digitized into large blocks paradoxically increases their recognizability. Such blurring led to significant enhancement of LO activation. Despite the preferential activation to objects, LO did not seem to be involved in the final, "semantic," stages of the recognition process. Thus, objects varying widely in their recognizability (e.g., famous faces, common objects, and unfamiliar three-dimensional abstract sculptures) activated it to a similar degree. These results are thus evidence for an intermediate link in the chain of processing stages leading to object recognition in human visual cortex.

Visual motion aftereffect in human cortical area MT revealed by functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) was used to measure local haemodynamic changes (reflecting electrical activity) in human visual cortex during production of the visual motion aftereffect, also known as the waterfall illusion. As in previous studies, human cortical area MT (V5) responded much better to moving than to stationary visual stimuli. Here we demonstrate a clear increase in activity in MT when subjects viewed a stationary stimulus undergoing illusory motion, following adaptation to stimuli moving in a single local direction. Control stimuli moving in reversing, opposed directions produced neither a perceptual motion aftereffect nor elevated fMRI levels postadaptation. The time course of the motion aftereffect (measured in parallel psychophysical tests) was essentially identical to the time course of the fMRI motion aftereffect. Because the motion aftereffect is direction specific, this indicates that cells in human area MT are also direction specific. In five other retinotopically defined cortical areas, similar motion-specific aftereffects were smaller than those in MT or absent.