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Biomedical subjects

Rafael Malach

Publications and source records attributed to Rafael Malach.

At least 19 recordsLinked to original sources

Extrinsic and intrinsic systems in the posterior cortex of the human brain revealed during natural sensory stimulation.

When exposing subjects to a continuous segment of an audiovisual movie, a large expanse of human cortex, especially in the posterior half of the cerebral cortex, shows stimulus-driven activity. However, embedded within this widespread activity, there are cortical regions whose activity is dissociated from the external stimulation. These regions are intercorrelated among themselves, forming a functional network, which largely overlaps with cortical areas previously shown to be deactivated by task-oriented paradigms. Moreover, the network of areas whose neuronal dynamics are associated with external inputs and the network of areas that appears to be intrinsically driven complement each other, providing coverage of most of the posterior cortex. Thus, we propose that naturalistic stimuli reveal a fundamental neuroanatomical partition of the human posterior cortex into 2 global networks: an "extrinsic" system, comprising areas associated with the processing of external inputs, and an "intrinsic" system, largely overlapping with the task-negative, default-mode network, comprising areas associated with--as yet not fully understood--intrinsically oriented functions.

Acoustic Stimulation↗

When the brain loses its self: prefrontal inactivation during sensorimotor processing.

A common theme in theories of subjective awareness poses a self-related "observer" function, or a homunculus, as a critical element without which awareness can not emerge. Here, we examined this question using fMRI. In our study, we compared brain activity patterns produced by a demanding sensory categorization paradigm to those engaged during self-reflective introspection, using similar sensory stimuli. Our results show a complete segregation between the two patterns of activity. Furthermore, regions that showed enhanced activity during introspection underwent a robust inhibition during the demanding perceptual task. The results support the notion that self-related processes are not necessarily engaged during sensory perception and can be actually suppressed.

Acoustic Stimulation↗

Sub-exemplar shape tuning in human face-related areas.

Although human face recognition performance shows high selectivity, even for unfamiliar faces, the neuronal circuitry underlying this high performance is poorly understood. Two extreme alternatives can be considered: either a "labeled-line" principle, in which subtle changes in face images lead to activation of differently tuned neuronal populations, or a coarse coding principle, where the high face selectivity is coded by the relative activation of broadly tuned neurons. In this study, we set to parametrically examine the shape and selectivity profile of face-related visual areas. To that end, we applied the functional magnetic resonance (fMR)-adaptation paradigm. Unfamiliar face stimuli were morphed into sets ranging from identical faces, through subtle morphing, to completely different exemplars. The fusiform face area (FFA) revealed high face sensitivity, so that even facial images perceived as belonging to the same individual (<35%) were sufficient to produce full recovery from adaptation. Interestingly, the psychophysical detectability of facial differences paralleled the release from fMR-adaptation. These results support the labeled-line model where high sensitivity to face changes is paralleled by narrow tuning of neuronal populations selective to each face image, and they suggest that fMR-adaptation is closely related to behavior. The results bear strong implications to the nature of face-related neuronal responses.

Adaptation, Physiological↗

Widespread functional connectivity and fMRI fluctuations in human visual cortex in the absence of visual stimulation.

To what extent does the visual system's activity fluctuate when no sensory stimulation is present? Here, we studied this issue by examining spontaneous fluctuations in BOLD signal in the human visual system, while subjects were placed in complete darkness. Our results reveal widespread slow fluctuations during such rest periods. In contrast to stimulus-driven activity, during darkness, functionally distinct object areas were fluctuating in unison. These fMRI fluctuations became rapidly spatially de-correlated (39% drop in correlation level, P < 0.008) during visual stimulation. Functional connectivity analysis revealed that the slow spontaneous fluctuations during rest had consistent and specific neuro-anatomical distribution which argued against purely hemodynamic noise sources. Control experiments ruled out eye closure, low luminance and mental imagery as the underlying sources of the spontaneous fluctuations. These results demonstrate that, when no stimulus is present, sensory systems manifest a robust level of slow organized fluctuation patterns.

Adult↗

Human brain activation during viewing of dynamic natural scenes.

To what extent do brains of different human individuals operate in a similar manner? Here we explored the organization and function of different brain regions under progressively more natural conditions. Applying an unbiased analysis, in which spatiotemporal activity patterns in one brain were used to 'model' activity in another brain, we found a striking level of voxel by voxel synchronization between individuals during free viewing of an audio-visual movie. This intersubject correlation was evident not only in primary and secondary visual and auditory areas, but also in association cortices. The results reveal a surprising tendency of individual brains to 'tick collectively' during natural vision. Moreover, our results demonstrate that the unitary nature of conscious experience in fact consists of temporally interleaved and highly selective activations in an ensemble of specialized regions, each of which 'picks-up' and analyses its own unique subset of stimuli according to its functional specialization. Applying reverse correlation to the movie stimuli provides a powerful methodology for revealing both known and unexpected functional specializations in those cortical areas activated by the movie.

Brain↗

Negative BOLD differentiates visual imagery and perception.

Recent studies emphasize the overlap between the neural substrates of visual perception and visual imagery. However, the subjective experiences of imagining and seeing are clearly different. Here we demonstrate that deactivation of auditory cortex (and to some extent of somatosensory and subcortical visual structures) as measured by BOLD functional magnetic resonance imaging unequivocally differentiates visual imagery from visual perception. During visual imagery, auditory cortex deactivation negatively correlates with activation in visual cortex and with the score in the subjective vividness of visual imagery questionnaire (VVIQ). Perception of the world requires the merging of multisensory information so that, during seeing, information from other sensory systems modifies visual cortical activity and shapes experience. We suggest that pure visual imagery corresponds to the isolated activation of visual cortical areas with concurrent deactivation of "irrelevant" sensory processing that could disrupt the image created by our "mind's eye."

Adult↗

Coupling between neuronal firing, field potentials, and FMRI in human auditory cortex.

Functional magnetic resonance imaging (fMRI) is an important tool for investigating human brain function, but the relationship between the hemodynamically based fMRI signals in the human brain and the underlying neuronal activity is unclear. We recorded single unit activity and local field potentials in auditory cortex of two neurosurgical patients and compared them with the fMRI signals of 11 healthy subjects during presentation of an identical movie segment. The predicted fMRI signals derived from single units and the measured fMRI signals from auditory cortex showed a highly significant correlation (r = 0.75, P < 10(-47)). Thus, fMRI signals can provide a reliable measure of the firing rate of human cortical neurons.

Adult↗

Retinotopic axis specificity and selective clustering of feedback projections from V2 to V1 in the owl monkey.

Cortical maps and feedback connections are ubiquitous features of the visual cerebral cortex. The role of the feedback connections, however, is unclear. This study was aimed at revealing possible organizational relationships between the feedback projections from area V2 and the functional maps of orientation and retinotopy in area V1. Optical imaging of intrinsic signals was combined with cytochrome oxidase histochemistry and connectional anatomy in owl monkeys. Tracer injections were administered at orientation-selective domains in regions of pale and thick cytochrome oxidase stripes adjacent to the border between these stripes. The feedback projections from V2 were found to be more diffuse than the intrinsic horizontal connections within V1, but they nevertheless demonstrated clustering. The clusters of feedback axons projected preferentially to interblob cytochrome oxidase regions. The distribution of preferred orientations of the recipient domains in V1 was broad but appeared biased toward values similar to the preferred orientation of the projecting cells in V2. The global spatial distribution of the feedback projections in V1 was anisotropic. The major axis of anisotropy was systematically parallel to a retinotopic axis in V1 corresponding to the preferred orientation of the cells of origin in V2. We conclude that the feedback connections from V2 to V1 might play a role in enhancing the response in V1 to collinear contour elements.

Animals↗

Detailed exploration of face-related processing in congenital prosopagnosia: 2. Functional neuroimaging findings.

Specific regions of the human occipito-temporal cortex are consistently activated in functional imaging studies of face processing. To understand the contribution of these regions to face processing, we examined the pattern of fMRI activation in four congenital prosopagnosic (CP) individuals who are markedly impaired at face processing despite normal vision and intelligence, and with no evidence of brain damage. These individuals evinced a normal pattern of fMRI activation in the fusiform gyrus (FFA) and in other ventral occipito-temporal areas, in response to faces, buildings, and other objects, shown both as line drawings in detection and discrimination tasks and under more naturalistic testing conditions when no task was required. CP individuals also showed normal adaptation levels in a block-design adaptation experiment and, like control subjects, exhibited evidence of global face representation in the FFA. The absence of a BOLD-behavioral correlation (profound behavioral deficit, normal face-related activation in the ventral occipito-temporal cortex) challenges existing accounts of face representation, and suggests that activation in these cortical regions per se is not sufficient to ensure intact face processing.

Adult↗

One picture is worth at least a million neurons.

How many neurons participate in the representation of a single visual image? Answering this question is critical for constraining biologically inspired models of object recognition, which vary greatly in their assumptions from few "grandmother cells" to numerous neurons in widely distributed networks. Functional imaging techniques, such as fMRI, provide an opportunity to explore this issue, since they allow the simultaneous detection of the entire neuronal population responding to each stimulus. Several studies have shown that fMRI BOLD signal is approximately proportional to neuronal activity. However, since it provides an indirect measure of this activity, obtaining a realistic estimate of the number of activated neurons requires several intervening steps. Here, we used the extensive knowledge of primate V1 to yield a conservative estimate of the ratio between hemodynamic response and neuronal firing. This ratio was then used, in addition to several cautious assumptions, to assess the number of neurons responding to a single-object image in the entire visual cortex and particularly in object-related areas. Our results show that at least a million neurons in object-related cortex and about two hundred million neurons in the entire visual cortex are involved in the representation of a single-object image.

Adult↗

Enhanced temporal non-linearities in human object-related occipito-temporal cortex.

To what extent does neural activation in human visual cortex follow the temporal dynamics of the optical retinal stimulus? Specifically, to what extent does stimulus evoked neural activation persist after stimulus termination? In the present study, we used functional magnetic resonance imaging (fMRI) to explore the resulting temporal non-linearities across the entire constellation of human visual areas. Gray-scale images of animals, houses and faces were presented at two different presentation rates - 1 and 4 Hz - and the fMRI signal was analyzed in retinotopic and in high order occipito-temporal visual areas. In early visual areas and the motion sensitive area MT/V5, a fourfold increase in stimulus presentation rate evoked a twofold increase in signal amplitude. However, in high order visual areas, signal amplitude increased only by 25%. A control experiment ruled out the possibility that this difference was due to signal saturation ('ceiling') effects. A likely explanation for the stronger non-linearities in occipito-temporal cortex is a persistent neuronal activation that continues well after stimulus termination in the 1 Hz condition. These persistent activations might serve as a short term (iconic) memory mechanism for preserving a trace of the stimulus even in its absence and for future integration with temporally correlated stimuli. Two alternative models of persistence (inhibitory and excitatory) are proposed to explain the data.

Adaptation, Physiological↗

Intersubject synchronization of cortical activity during natural vision.

To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to "model" activity in another brain, we found a striking level of voxel-by-voxel synchronization between individuals, not only in primary and secondary visual and auditory areas but also in association cortices. The results reveal a surprising tendency of individual brains to "tick collectively" during natural vision. The intersubject synchronization consisted of a widespread cortical activation pattern correlated with emotionally arousing scenes and regionally selective components. The characteristics of these activations were revealed with the use of an open-ended "reverse-correlation" approach, which inverts the conventional analysis by letting the brain signals themselves "pick up" the optimal stimuli for each specialized cortical area.

Adult↗

Functional analysis of the periphery effect in human building related areas.

Several studies have shown that a region in the anterior collateral sulcus (CoS) and a region in the vicinity of the transverse occipital sulcus (TOS) are preferentially activated by images of buildings and scenes. We have found recently that these regions show a strong activation bias to stimuli located in the peripheral visual field. We explore in detail the source of this "periphery" effect. Our results show that the periphery effect can be generated by a large single object occupying the peripheral visual field as well as by multiple small peripheral objects. We also investigated whether the periphery effect was related to the annular shape used in conventional mapping of the visual field periphery and found that the mere presence of a stimulus in the visual field periphery, regardless of object shape, is sufficient to enhance activation. We also found that a small bias toward the peripheral visual field was shown even when the stimulated areas in the central and peripheral parts of the visual field are equated. Finally, our results demonstrate that the periphery effect shows object selectivity that can be obtained even with face images, which are the non-optimal stimulus for this region. In summary, our study shows that the building-related CoS and TOS manifest a true but graded retinotopic bias toward the peripheral visual field.

Adult↗

Rapid completion effects in human high-order visual areas.

Object completion is an inherent property of visual recognition in which objects can be accurately perceived in the presence of substantial obstructions. We have previously shown [Cereb. Cortex 12 (2002) 163] that high-order human object areas are driven partially by local object fragments and partially by global completion effects. Here we explored, through a backward masking paradigm, whether the balance of local and global processing is time dependent, that is, to what extent completion effects evolve at a different time compared to local image representations. In two separate experiments, subjects were presented with three types of images: (a) unobstructed line drawings of animal shapes ("whole"), (b) the same shapes obstructed by a set of parallel stripes ("grid"), and (c) a scrambled version of b in which the stripe position was shifted horizontally, disrupting the relative position of image regions but maintaining the local feature distribution ("scrambled"). Images were presented either for 60 or 250 ms followed by a mask. Both behavioral and fMRI findings from high-order occipitotemporal object areas showed consistently that object selectivity emerges at the same time as the local feature representation. Thus, object completion effects were evident at the same relative magnitude (LO: 0.5 +/- 0.3 and 0.58 +/- 0.04; pFs: 0.62 +/- 0.3 and 0.6 +/- 0.04; 60 and 250 ms, respectively) even at the short presentation durations when overall object activation was greatly reduced.

Adult↗

The human visual cortex.

The discovery and analysis of cortical visual areas is a major accomplishment of visual neuroscience. In the past decade the use of noninvasive functional imaging, particularly functional magnetic resonance imaging (fMRI), has dramatically increased our detailed knowledge of the functional organization of the human visual cortex and its relation to visual perception. The fMRI method offers a major advantage over other techniques applied in neuroscience by providing a large-scale neuroanatomical perspective that stems from its ability to image the entire brain essentially at once. This bird's eye view has the potential to reveal large-scale principles within the very complex plethora of visual areas. Thus, it could arrange the entire constellation of human visual areas in a unified functional organizational framework. Here we review recent findings and methods employed to uncover the functional properties of the human visual cortex focusing on two themes: functional specialization and hierarchical processing.

Animals↗

Face-selective activation in a congenital prosopagnosic subject.

Congenital prosopagnosia is a severe impairment in face identification manifested from early childhood in the absence of any evident brain lesion. In this study, we used fMRI to compare the brain activity elicited by faces in a congenital prosopagnosic subject (YT) relative to a control group of 12 subjects in an attempt to shed more light on the nature of the brain mechanisms subserving face identification. The face-related activation pattern of YT in the ventral occipito-temporal cortex was similar to that observed in the control group on several parameters: anatomical location, activation profiles, and hemispheric laterality. In addition, using a modified vase-face illusion, we found that YT's brain activity in the face-related regions manifested global grouping processes. However, subtle differences in the degree of selectivity between objects and faces were observed in the lateral occipital cortex. These data suggest that face-related activation in the ventral occipito-temporal cortex, although necessary, might not be sufficient by itself for normal face identification.

Adult↗

Large-scale mirror-symmetry organization of human occipito-temporal object areas.

We have combined functional maps of retinotopy (eccentricity and meridian mapping), object category, and motion in a group of subjects to explore the large-scale topography of higher-order object areas. Our results reveal seven consistent category-related entities situated in the occipito-temporal cortex adjoining early visual areas. These include two face-related regions, three object-related regions, and two building-related regions. Interestingly, this complex category-related pattern is organized in a large-scale dorso-ventral mirror symmetry of object category. Furthermore, correlating this pattern to the map of visual field eccentricity, we found that the entire network of areas could be related to a single and unified eccentricity map. We hypothesize that this large-scale organization points to a possible development of high-order object areas through extension and specialization of a single proto-representation.

Brain Mapping↗

Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration.

PURPOSE: To investigate a method that uses hyperacuity, the Macular Computerized Psychophysical Test (MCPT), to evaluate the central macular visual field in patients with age-related macular degeneration (AMD). DESIGN: Prospective case-control study of a diagnostic test. PARTICIPANTS AND CONTROLS: One hundred eight eyes of 108 Patients with AMD and 51 eyes of 51 age-matched patients with no retinal disease. Patients with AMD included 32 (30%) patients with choroidal neovascularization (CNV), 23 (21%) with geographic atrophy (GA), 35 (32%) with AMD with high-risk characteristics (HRC), and 18 (17%) with early AMD with non-HRC. TESTING: Each subject underwent the MCPT, in which a virtual line composed of dots (white dots on a black background, maximal contrast) is flashed across different macular loci to a perifoveal radius of 7 degrees. Patients' responses were recorded and automatically analyzed using a specific algorithm developed before the onset of the study. All patients also underwent a supervised Amsler grid examination on the encounter before or after the MCPT in random order. MAIN OUTCOME MEASURES: Distortion, scotoma, or blurring perceived by the patient after a swift change of fixation was considered positive on the MCPT. Any perception of distortion, scotoma, or blurring was considered positive on the Amsler grid. RESULTS: Of the 32 patients with CNV, 30 (94%) were found positive on the MCPT and 11 (34%) were found positive on the Amsler grid. Of the 23 GA patients, 21 (91%) were found positive on the MCPT and 7 (30%) were found positive on the Amsler grid. Of the 35 HRC patients, 28 (80%) were found positive on the MCPT and 3 (9%) were found positive on the Amsler grid, and of the 18 early AMD with non-HRC patients, 8 (44%) were found positive on the MCPT and 3 (17%) were found positive on the Amsler grid. Of the 51 controls, 3 (6%) were positive on the MCPT and 1 (2%) was positive on the Amsler grid. CONCLUSIONS: The MCPT was superior to the Amsler grid in detecting AMD-related lesions in this cohort. Studies are underway to determine whether the MCPT is feasible for home monitoring to provide early detection of progression to CNV.

Aged↗