The Unit on Cognitive Neurophysiology and Imaging (UCNI) is working closely together with the neighboring Neurophysiology Imaging Facility (NIF) to elaborate the relationship between electrical neural brain signals signals, measurable with microelectrodes, and functional neuroimaging signals, measured with functional magnetic resonance imaging (fMRI). Based on research in the last decades, neurophysiology and imaging studies in general agreement regarding the manner in which visual stimuli are processed in the cortex. A number of studies have, however, found differences between the techniques under conditions in which cognitive variables such as attention or subjective perception are dissociated from the physical stimulus. For example, during certain visual illusions, the perceptual suppression of a salient visual pattern can results in significant decrease in the fMRI signal, while not affecting the measured electrical activity at all. We are interested in the basis of this discrepancy, since it might provide insights into the relationship between these two signals.? ? We have been researching along several lines to elucidate the neural underpinnings of the fMRI signal under conditions in the perceptual state is dissociated from the physical stimulation. Our first approach has used the novel paradigm called generalized flash suppression, described in another project of this annual report. Using this paradigm, we measured the fMRI signal and single-neuron response in the primary visual cortex (V1) of monkeys reporting whether they perceived a salient target. On half of the trials, where the target appeared visible, the responses were high in both signals, as one would expect. However, on the other half of the trials, where the target disappeared, the fMRI responses showed a major drop while the neural responses remained steady. This dissociation of brain signals during perceptual suppression solves a major mystery in the literature, indicating that it is neither the species difference (human vs. monkey) nor the specific paradigm differences that account for the observed discrepancy. Instead, the fMRI and neural signals are inherently different under condition in which perception does not match the physical stimulus condition.? ? We investigated this initial observation in greater detail using multicontact electrodes, permitting the simultaneous monitoring of different layers of cortical function. The mammalian cortex is a complex structure that is highly organized in its lamination. In this investigation, we found that one aspect of the electrical activity (specifically, the """"""""local field potential current source density"""""""") was modulated during perceptual suppression, and that this modulation was restricted to the upper visual layers. These more superficial layers are heavily involved in connections between different cortical areas, leading to the possibility that (1) cortico-cortico communication is critical for shaping perception and (2) the fMRI signal is particularly sensitive to currents generated in the upper cortical layers.? ? In our present work, we are further investigating the laminar nature of neural activity as it relates to the functional MRI signal. We have expanded our experimental repertoire to now include neurophysiological recordings inside the magnetic bore. This approach permits us to investigate spontaneous activity fluctuations in the resting brain (which is, in fact, never at rest in the sense of being inactive). By looking at the coupling of the two types of signals under different states of brain activation ranging from sleep to full attention, we hope to better understand how the fMRI signal can be derived from the neural signal, and whether the relationship between these two signals is constant as a function of arousal level. We expect that these collective findings, to be published shortly, will again have important implications for a large number of human studies that rely upon the blood-coupled fMRI signal to interpret underlying brain function.