The research project entitled ?Neurophysiology of Visual Perception? aims to understand neural processes involved the brain's registration and interpretation of the visual world. A large portion of the primate brain is devoted to the faculty of vision. Vision is an inferential process that begins with a pattern of focused light projected onto the flat retina. From this projection, the brain analyzes shape, color, depth, and motion in order to perceive objects and scenes. In the last decades, neurophysiological studies have unveiled much of the basic sensory machinery that underlies this process. Neurons apparently specialized in their activity to respond to basic visual features, to spatial patterns, to objects, and sometimes even to individual faces, are plentiful in the primate brain. Yet, most neurophysiologists would concede that while these studies provide an excellent basis for understanding how visual stimuli are received and perhaps encoded, little is known about the mechanisms that relate directly to the formation of a percept. Our main aim is therefore to study known elements of visual processing, with particular regard to how these elements contribute to the formation and maintenance of a percept. Our approach presently has two main foci. First, we have been integrating electrophysiological and imaging approaches to elucidate the role of visual cortex in perceptual suppression. Second, we have been examining the complex interplay between the thalamus and cortex in an attempt to understand how these tightly linked structures work together during normal visual processing, as well as states of relaxation. In the past year, we have made great progress in understanding a potentially important discrepancy that has emerged between neurophysiological studies of perception and comparable studies in the vast human neuroimaging literature. Namely, experiments in the respective fields have disagreed on the seemingly fundamental question of whether or not the primary visual cortex (also known as V1), a large cortical area present in all mammals, is directly involved in the visual perception of a stimulus. While direct neural measurements have suggested, perhaps surprisingly, that cells in this area only minimally contribute to the formation of a percept, human neuroimaging studies have shown a tight linkage between V1 activity and a perceptual state. We tested whether the discrepancy, which has served as an obstacle in our understanding of neural mechanisms of visual perception, arises because of species differences, differences in the paradigms used to test the question, or differences in the very nature of the signals being measured (electrophysiological vs. imaging, the latter measured with functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast). Using a novel paradigm in which the perceptual visibility of a salient stimulus varied from trial to trial, we tested non-human primate (NHP) subjects in both electrophysiological and fMRI conditions. We asked whether the (perceptual) suppression of a stimulus would be evident in the signals collected in area V1 using the two techniques. We found that the strong perceptual modulation seen in human neuroimaging studies was also observed in NHPs, and that in the very same NHP subjects there was no evidence of percept-related responses among single neurons. Thus, within the same species, and using the same paradigm, the two different signals offered a very different view of activity in this part of the brain, as it related to visual perception. The neurophysiological studies have been carried out over the last year by members of the Unit on Cognitive Neurophysiology and Imaging (UCNI), in the Laboratory of Neuropsychology (LN). In addition, the project has drawn heavily upon resources made available from the Neurophysiology Imaging Facility (NIF). Several subprojects have been launched to advance our understanding of the basis of these differences. One involves the examination of perceptual modulation of the fMRI signal using the exact same paradigm in human subjects. This ongoing work is in collaboration with the Section on Advanced Functional Imaging in NINDS. Another project involves trying to understand whether a microelectrode contains more ?information? about a perceptual state than is present in the spiking responses of neurons. This information, if present in other signals, for example, might provide insights into why the fMRI signals show such strong correspondence with the perceptual state. In an extramural collaboration with researchers at the University of Texas in Houston, we have found that, by combining different electrical signals measure from the same recording electrode, it is possible to gain a high degree of accuracy in ?decoding? the perceptual state of the animal. The success of this approach, which resembles the increasingly popular ?mind-reading? used by some fMRI researchers, was quite a surprise given the minimal correspondence with the perceptual state exhibited by individual neurons. Thus, it appears that there is more perceptual information present in electrical recordings than traditionally thought. This fact might have implications for understanding the link between the electrical and fMRI signals. It may also have practical implications as well, such as for techniques that require decoding of the neural signal, such as neural prosthesis. Additional projects in our group have investigated more deeply how the functional connectivity of the thalamocortical system might impact perceptual processing, as well as the fMRI signal. One current project uses multicontact electrodes spanning the cortical thickness to identify which layers show particularly prominent modulation as a function of the perceptual state in the task described above. This study aims to understand whether the measured fMRI signal is more tightly correlated with activity in some layers than in others. And given the strict laminar segregation of neurons projecting to cortical or subcortical targets, another project exploits laminar activity differences to evaluate thalamocortical interplay during the resting state, as well as during natural vision. It is well known that the cerebral cortex and thalamus evolved in parallel, but they are usually studied in isolation. We are therefore measuring signals from cortical and thalamic targets simultaneously to understand how activity changes in one structure covary with those in the other. In order to best study the response of the system, one project, carried out in combination with the Section on Cognitive Neuroscience, has involved perturbing the system with an injected pharmacological agent, and then observing the effects on the whole system with both microelectrodes and fMRI. This study, which fully exploits the NHP neuroimaging environment, permits us to chemically modulate the activity of a secondary thalamic nucleus, and then monitor, both electrophysiologically and using fMRI, the effect of this temporary """"""""lesion"""""""" on activity elsewhere in the brain. Ultimately, the main research objective of our laboratory always centers upon studying visual perception. For this reason, we are continually developing new behavioral paradigms in normal human subjects, to serve as the basis for NHP experiments in the future. This approach has been greatly successful in the past, in which studies of human psychophysics have been followed by corresponding neurophysiological experiments. One example is the neurophysiology of face perception, which we have explored extensively in the past and plan, and which we plan to begin with again during the next fiscal year.

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; Rhodes, Gillian; Muller, Kai-Markus et al. (2005) The dynamics of visual adaptation to faces. Proc Biol Sci 272:897-904

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