Studying the neural basis of visual perception is inherently challenging because of the dissimilar nature of psychological and biological measurements. For the psychologist, it is possible to speak precisely about subjective quantities in vision such as brightness or depth, yet psychophysical methods are limited in their capacity to deliver insights into specific brain mechanisms. Sensory physiologists, on the other hand, can be quantitative about the magnitude or duration of a neural response, but often need to speculate about the relation of such responses to perception. Thus studying neural processes underlying perception requires the marriage of experimental tools having distinct historical origins, a process that continues to evolve. ? ? We have taken the approach of using visual illusions to destabilize vision into a series of perceptual alternations, and thereby ask what neural processes correlate with the changing perceptual states. In the last years, we developed a number of such paradigms that are useful for testing nonhuman primates. In the past year, we have been focusing on one paradigm in particular, termed generalized flash suppression (GFS). In GFS, a salient visual target is presented on a screen, and appears to suddenly vanish when a number of surrounding dots are presented in the periphery. When the target disappears, it can remain invisible for several seconds, and there are a number of stimulus parameters govern the probability that the target disappears on any particular trial. For some stimulus settings, the target is seen to disappear on roughly 50% of the trials, but remain visible on the other 50%. In this case, what processes in the brain determine whether the target is seen on any particular trial?? ? Many studies in the past decade have investigated this type of question using microelectrode recordings in monkeys in functional MRI (fMRI) studies in humans. While there is general agreement about the involvement of different cortical areas within a paradigm/species, the two basic approaches, when contrasted with each other, have led to flatly contradictory results. Human imaging results have repeatedly shown that the primary visual cortex is strongly modulated according the visibility of a stimulus, while monkey neurophysiology studies have shown that it is the physical stimulus, rather than the percept, that is signaled by neurons there. ? ? We have recently made great headway in solving this conundrum, by directly comparing electrophysiological and fMRI studies in the same nonhuman primate subjects. Using GFS, we found that the previous differences were not ascribable to either species differences, or differences in the paradigm. Instead, there is a real and consistent difference between the fMRI responses and the neural response. In other words, by monitoring the fMRI signal of a monkey's brain, it is possible to determine whether a stimulus is visible or invisible, while, perhaps ironically, it is impossible to determine this by measuring the responses of individual neurons in the same area. This work has great and unexpected implications for the use of fMRI at studying brain processes, a point that we elaborate upon in a different section of this report. ? ? In a related subproject, we have examined the role of visual thalamic structures in supporting a visual percept. We used electrophysiological techniques to examine the pulvinar nucleus and the lateral geniculate nucleus, each of which is heavily interconnected with the visual cortex. We found that responses in the lateral geniculate nucleus were not affected by the visibility of the target (in this sense they were similar to neurons in the primary visual cortex). In contrast, we found that responses in the visual pulvinar nucleus were modulated significantly according to whether the monkey reported seeing a target on a given trial or not. These findings are helping us to how understand disparate by heavily interconnected parts of the brain act together as a sort of ? perceptual circuit.? ? We are presently extending this work by combining local pharmacological approaches with both visualization in MRI, as well as behavior, to further elucidate the role of the pulvinar in perception. In a novel paradigm, we are able to inject an inhibitory agent, along with an MR-visible contrast agent, into the brain of awake nonhuman primates as they perform a visual task. Using fMRI, we track how inactivating certain portions of their brain interferes with processing in various neural circuits, and over what time course. Through such reversible inactivation experiments, we are able to test hypotheses about the critical elements involved in such perceptual circuits as mentioned above. There are three publications in the preparation or submission stage of this project.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Intramural Research (Z01)
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Müller, K-M; Wilke, M; Leopold, D A (2009) Visual adaptation to convexity in macaque area V4. Neuroscience 161:655-62
Shmuel, Amir; Leopold, David A (2008) Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest. Hum Brain Mapp 29:751-61
Maier, Alexander; Logothetis, Nikos K; Leopold, David A (2007) Context-dependent perceptual modulation of single neurons in primate visual cortex. Proc Natl Acad Sci U S A 104:5620-5
Wang, Zhisong; Maier, Alexander; Leopold, David A et al. (2007) Single-trial evoked potential estimation using wavelets. Comput Biol Med 37:463-73
Wang, Zhisong; Maier, Alexander; Leopold, David A et al. (2006) Relaxation-based multichannel signal combination (RELAX-MUSIC) for ROC analysis of percept-related neuronal activity. IEEE Trans Biomed Eng 53:2615-8
Leopold, David A; Bondar, Igor V; Giese, Martin A (2006) Norm-based face encoding by single neurons in the monkey inferotemporal cortex. Nature 442:572-5
Fukunaga, Masaki; Horovitz, Silvina G; van Gelderen, Peter et al. (2006) Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during extended rest and early sleep stages. Magn Reson Imaging 24:979-92
Leopold, David A; Maier, Alexander (2006) Neuroimaging: perception at the brain's core. Curr Biol 16:R95-8
Wilke, Melanie; Logothetis, Nikos K; Leopold, David A (2006) Local field potential reflects perceptual suppression in monkey visual cortex. Proc Natl Acad Sci U S A 103:17507-12
Leopold, David A; Wilke, Melanie (2005) Neuroimaging: seeing the trees for the forest. Curr Biol 15:R766-8

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