Wim Vanduffel

The Retinotopy of Visual Spatial Attention

We used high-field (3T) functional magnetic resonance imaging (fMRI) to label cortical activity due to visual spatial attention, relative to flattened cortical maps of the retinotopy and visual areas from the same human subjects. In the main task, the visual stimulus remained constant, but covert visual spatial attention was varied in both location and load. In each of the extrastriate retinotopic areas, we found MR increases at the representations of the attended target. Similar but smaller increases were found in V1. Decreased MR levels were found in the same cortical locations when attention was directed at retinotopically different locations. In and surrounding area MT+, MR increases were lateralized but not otherwise retinotopic. At the representation of eccentricities central to that of the attended targets, prominent MR decreases occurred during spatial attention.

Comparative mapping of higher visual areas in monkeys and humans

The advent of functional magnetic resonance imaging (fMRI) in non-human primates has facilitated comparison of the neurobiology of cognitive functions in humans and macaque monkeys, the most intensively studied animal model for higher brain functions. Most of these comparative studies have been performed in the visual system. The early visual areas V1, V2 and V3, as well as the motion area MT are conserved in humans. Beyond these areas, differences between human and monkey functional organization are increasingly evident. At the regional level, the monkey inferotemporal and intraparietal complexes appear to be conserved in humans, but there are profound functional differences in the intraparietal cortex suggesting that not all its constituent areas are homologous. In the long term, fMRI offers opportunities to compare the functional anatomy of a variety of cognitive functions in the two species.

Visual Motion Processing Investigated Using Contrast Agent-Enhanced fMRI in Awake Behaving Monkeys

To reduce the information gap between human neuroimaging and macaque physiology and anatomy, we mapped fMRI signals produced by moving and stationary stimuli (random dots or lines) in fixating monkeys. Functional sensitivity was increased by a factor of approximately 5 relative to the BOLD technique by injecting a contrast agent (monocrystalline iron oxide nanoparticle [MION]). Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines). These regions sensitive for moving dots are largely in agreement with monkey single unit data and (except for V3A) with human fMRI results. Moving lines activate some regions that have not been previously implicated in motion processing. Overall, the results clarify the relationship between the motion pathway and the dorsal stream in primates.

Stereopsis activates V3A and caudal intraparietal areas in macaques and humans.

Stereopsis, the perception of depth from small differences between the images in the two eyes, provides a rich model for investigating the cortical construction of surfaces and space. Although disparity-tuned cells have been found in a large number of areas in macaque visual cortex, stereoscopic processing in these areas has never been systematically compared using the same stimuli and analysis methods. In order to examine the global architecture of stereoscopic processing in primate visual cortex, we studied fMRI activity in alert, fixating human and macaque subjects. In macaques, we found strongest activation to near/far compared to zero disparity in areas V3, V3A, and CIPS. In humans, we found strongest activation to the same stimuli in areas V3A, V7, the V4d topolog (V4d-topo), and a caudal parietal disparity region (CPDR). Thus, in both primate species a small cluster of areas at the parieto-occipital junction appears to be specialized for stereopsis.

The Representation of Tool Use in Humans and Monkeys: Common and Uniquely Human Features

Though other species of primates also use tools, humans appear unique in their capacity to understand the causal relationship between tools and the result of their use. In a comparative fMRI study, we scanned a large cohort of human volunteers and untrained monkeys, as well as two monkeys trained to use tools, while they observed hand actions and actions performed using simple tools. In both species, the observation of an action, regardless of how performed, activated occipitotemporal, intraparietal, and ventral premotor cortex, bilaterally. In humans, the observation of actions done with simple tools yielded an additional, specific activation of a rostral sector of the left inferior parietal lobule (IPL). This latter site was considered human-specific, as it was not observed in monkey IPL for any of the tool videos presented, even after monkeys had become proficient in using a rake or pliers through extensive training. In conclusion, while the observation of a grasping hand activated similar regions in humans and monkeys, an additional specific sector of IPL devoted to tool use has evolved in Homo sapiens, although tool-specific neurons might reside in the monkey grasping regions. These results shed new light on the changes of the hominid brain during evolution.

Bottom-Up Dependent Gating of Frontal Signals in Early Visual Cortex

The frontal eye field (FEF) is one of several cortical regions thought to modulate sensory inputs. Moreover, several hypotheses suggest that the FEF can only modulate early visual areas in the presence of a visual stimulus. To test for bottom-up gating of frontal signals, we microstimulated subregions in the FEF of two monkeys and measured the effects throughout the brain with functional magnetic resonance imaging. The activity of higher-order visual areas was strongly modulated by FEF stimulation, independent of visual stimulation. In contrast, FEF stimulation induced a topographically specific pattern of enhancement and suppression in early visual areas, but only in the presence of a visual stimulus. Modulation strength depended on stimulus contrast and on the presence of distractors. We conclude that bottom-up activation is needed to enable top-down modulation of early visual cortex and that stimulus saliency determines the strength of this modulation.

The Processing of Visual Shape in the Cerebral Cortex of Human and Nonhuman Primates: A Functional Magnetic Resonance Imaging Study

We compared neural substrates of two-dimensional shape processing in human and nonhuman primates using functional magnetic resonance (MR) imaging in awake subjects. The comparison of MR activity evoked by viewing intact and scrambled images of objects revealed shape-sensitive regions in occipital, temporal, and parietal cortex of both humans and macaques. Intraparietal cortex in monkeys was relatively more two-dimensional shape sensitive than that of humans. In both species, there was an interaction between scrambling and type of stimuli (grayscale images and drawings), but the effect of stimulus type was much stronger in monkeys than in humans. Shape- and motion-sensitive regions overlapped to some degree. However, this overlap was much more marked in humans than in monkeys. The shape-sensitive regions can be used to constrain the warping of monkey to human cortex and suggest a large expansion of lateral parietal and superior temporal cortex in humans compared with monkeys.

Repeated fMRI using iron oxide contrast agent in awake, behaving macaques at 3 Tesla.

Iron oxide contrast agents have been employed extensively in anesthetized rodents to enhance fMRI sensitivity and to study the physiology of cerebral blood volume (CBV) in relation to blood oxygen level-dependent (BOLD) signal following neuronal activation. This study quantified the advantages of exogenous agent for repeated neuroimaging in awake, nonhuman primates using a clinical 3 Tesla scanner. A monocrystalline iron oxide nanoparticle (MION) solution was injected at iron doses of 8 to 10 mg/kg in two macaque monkeys. Adverse behavioral effects due to contrast agent were not observed in either monkey using cumulative doses in excess of 60 mg/kg. Relative to BOLD imaging at 3 Tesla, MION increased functional sensitivity by an average factor of 3 across the brain for a stimulus of long duration. Rapid stimulus presentation attenuated MION signal changes more than BOLD signal changes, due to the slower time constant of the blood volume response relative to BOLD signal. Overall, the contrast agent produced a dramatic improvement in functional brain imaging results in the awake, behaving primate at this field strength. (c) 2002 Elsevier Science (USA).

Similarities and differences in motion processing between the human and macaque brain: evidence from fMRI.

The present report reviews a series of functional magnetic resonance imaging (fMRI) activation studies conducted in parallel in awake monkeys and humans using the same motion stimuli in both species. These studies reveal that motion stimuli engage largely similar cortical regions in the two species. These common regions include MT/V5 and its satellites, of which FST contributes more to the human motion complex than is generally assumed in human imaging. These results also establish a direct link between selectivity of MT/V5 neurons for speed gradients and functional activation of human MT/V5 by three-dimensional (3D) structure from motion stimuli. On the other hand, striking functional differences also emerged: in humans V3A and several regions in the intraparietal sulcus (IPS) are much more motion sensitive than their simian counterparts.

Default Mode of Brain Function in Monkeys

Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.