The research project entitled """"""""Neurophysiology of Visual Perception"""""""" aims to understand neural processes involved in 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. Recent findings suggest that linking perception to the activity of single neurons may be difficult because perception may emerge from processes that are inherently interactive, involving interplay between different cortical and subcortical areas. Even such fundamental issues as the flow of visual information through the visual cortex during normal vision remains a topic of speculation. The present project thereby tries to understand at a deeper level how the basic elements of our visual perception emerge. These elements range from the subjective visibility of a salient target, to the recognition of an individual's face. One of our approaches to studying these questions has been to use stimuli for which a percept can be dissociated from a physical stimulation condition. Dissociation of sensation and perception is well-known feature of the brain, and is perhaps best illustrated by considering the vivid visual world that one experiences during a night time dream, when the eyes are closed. In the laboratory, a number of visual illusions provide a controlled way of studying this dissociation, using stimuli that are bistable in nature--that is, the percept they elicit alternates back and forth in time as the stimulus remains constant. To understand the nature of these perceptual reversals, we are studying the basis of this perceptual alternation directly with microelectrodes and indirectly with functional magnetic resonance imaging (fMRI), in the nonhuman primate (NHP). NHPs are trained to report their subjective impression of a variety of different stimulus types, and the neural measurements are then tied to their behavioral responses. Ultimately, this approach has permitted us to dissociate those aspects of the neural responses that are passive and automatic from those that relate directly to the generation of a subjective percept. Our main objective with this research is to gain a better understanding of the large-scale functioning of the visual processing stream. In addition, the research touches upon a number of very old and provocative questions related to the very nature of subjective perception and consciousness. In the present project we are beginning to use the combination of two techniques that provide alternate perspectives on brain activity. In contrast to nearly every other laboratory in the world, the NHP subjects in our studies participate in both electrophysiology and functional imaging experiments in the same study, and sometimes at precisely the same time The combined techniques approach allows us to understand how 1) how the activity of individual neurons at different stages of visual processing correspond to a subjective perceptual state, 2) how the hemodynamic-based (blood-oxygenation level dependent--BOLD) signals measured with fMRI over large regions of the same animal's brain corresponds to the same perceptual state, and 3) how the electrophysiological and BOLD signals may differ in their registration of perceptual events. The last of these points is born out of a growing suspicion from human fMRI studies that the two signals actually measure different aspects of the brain's processing. Understanding this link, as it relates to visual perception, is crucial for the interpretation of the many human fMRI studies that have studied these and similar issues. We are hopeful that such clarifications will represent a great step forward in our understanding of perceptual processes in the brain, as well as the capacity for human fMRI to tap into the neural mechanisms that underlie them. The present project is being carried out by members of the Unit on Cognitive Neurophysiology and Imaging (UCNI), in the Laboratory of Neuropsychology (LN). In addition, it draws heavily upon resources made available from the Neurophysiology Imaging Facility (NIF), a shared core facility founded in the beginning of 2004. In the past year, our group has concentrated on setting up both the electrophysiology and imaging related to testing in this project. The electrophysiology consists of multielectrode extracellular recordings in traditional shielded testing booths, while the functional imaging is done in the Bruker 4.7T vertical scanner in the NIF facility. The NIF scanner is one of the few in the world dedicated to the imaging of awake, behaving NHPs. In the past year, the NIF has undergone an intended transition from its primary use for anesthetized anatomical scans to becoming mostly dedicated to imaging awake animals performing behavioral tasks. There are a number of challenges that we are presently overcoming to accomplish this goal. These include developing a dynamic compensation for changing field inhomogeneities that arise from movements, including even breathing and swallowing, of the subject. Also, animals must be acclimated to the enclosed and noisy testing environment of the scanner bore. Finally, functional scanning paradigms must be designed to fit with the timing of fixation requirements and reward acquisition that characterize behavioral paradigms in the behaving monkey. In the past year, we have overcome a number of hardware difficulties in order to bring the awake monkey scanning to the verge of obtaining viable functional images. In addition, we have recently begun the process of upgrading our acquisition system to become multichannel and scalable for parallel imaging, a step that should greatly improve the speed and quality of functional scanning in behaving NHPs. Finally, NIF has recently purchased a specialized multichannel neurophysiology amplifier system that will permit recordings of neural signals inside the scanner itself. This innovation will make it possible to monitor simultaneously neural and BOLD signals in the same NHP on the same trials, permitting a direct assessment of the similarity or difference in perception-related signals expressed through the two techniques. The UCNI group has, similarly, devoted much of the last year to setting up the neurophysiological recordings. We have during that time developed and implanted a new style of head holder and recording chamber and are, within just days or weeks, about to begin our first neurophysiological recording sessions. We have made provisions to record from two brain areas simultaneously, with multiple electrodes occupying each site. The animals involved have already been accustomed to working both on the electrophysiological and magnet-testing environments, so that these recordings can be compared directly with functional maps obtained in the same subject. We are applying this approach to each of the sub-projects in the laboratory, as we believe that this combination is likely to provide considerably deeper insights than either technique alone.

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
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
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
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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