The Neural Basis of Functional MRI Responses

National Institute Of Mental Health

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Abstract

The mapping of activity in the brain using functional magnetic resonance imaging (fMRI) has become among the most important tools for both basic neuroscience research and clinical studies of brain disorders. At its core, fMRI represents a readout of local changes in blood flow that is most often derived from local changes in neural activity. Since blood flow and neural activity operate by entirely different principles, pinpointing their specific connection has been elusive and seems to depend on a number of factors. This is not surprising, for how can one make a one-to-one mapping between a specific pattern of activity among millions of neurons in a voxel to a slow change of single scalar values measured as the local the hemodynamic signal? Frustrating as the problem is, the topic is of great importance, since any clues about the link to local neural activity or ascending neuromodulation can have wide-reaching consequences for interpreting results in humans, including in psychiatric patients. While our laboratory does not focus on the study of neurovascular coupling per se, we do undertake experiments that bring new insights into the interpretation of the hemodynamic fMRI signal. For example we are studying the nature of local neural diversity of in the spiking responses to different types of signals, and how this bears on the hemodynamic responses from the same voxel or area. We are also investigating the relationship between activity in large-scale functional MRI networks across the brain to local neural activity measured at a single position. In the past year, we have made great progress using natural stimuli to understand aspects of the brain's functional organization that was difficult to ascertain using either single unit recordings or fMRI mapping. Several years ago, we demonstrated that during the free viewing of naturalistic videos reliably stimulated the visual system, such that the neural activation time course throughout the visual brain was consistent across multiple presentations. However, when we measure the activity of face patch neurons within a given voxel, there was a remarkable diversity of neural contributions. Neighboring neurons were often independent in their response time courses. How does this local heterogeneity shape the fMRI time courses? In the past year, we have drawn a surprising conclusion from studies in which we mapped fMRI activity based upon single neurons. Namely, in its natural mode of operation, the visual cortex is not composed of discrete, functionally homogeneous areas that process stimuli in a stepwise fashion. Instead, more broadly specialized regions are pervaded by parallel functional subnetworks, which contribute to the functioning of multiple brain areas. The operational division of labor, therefore, is not segregated spatially across the cortical surface, but is instead shared by subnetworks of neurons inhabiting faraway areas. This study, which combined fMRI and neural recordings, is due to be published shortly. A related study from our lab asks whether the spontaneous covariation of fMRI and neural signals during rest matches is similarly uncorrelated, and whether the spontaneous maps of a neuron match its visually driven maps. For this we simultaneously recorded single-unit and fMRI responses inside the MR scanner. As the technical hurdles associated with this type of work are immense, we needed to o develop and acquire MR-compatible electrodes, microdrive, suitable RF coils, preamplifiers, cables, and filters to achieve such simultaneous recording. In the past year, we have discovered that, in contrast to visual responses, the fMRI mapping of spontaneous activity is more homogeneous and more restricted across cortical and subcortical areas. The two studies together aim to provide insight into the nature of fMRI responses, including the local neurovascular relationship, as well as the network layout principles of high-level vision. In the past year, we have also taken steps to extend this work to the study of the basal forebrain, a small area that projects broadly to the cerebral cortex. We previously showed the basal forebrain is centrally involved in regulating spontaneous signals throughout the telencephalon during rest. This structure may be a particularly important contributor to fMRI signals across the brain, including the brain-wide networks that are commonly studied in clinical research.