The Neural Underpinnings of Functional MRI Networks

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

The capacity to noninvasively track dynamic activity patterns from spatially resolved structures deep inside the human brain began with the emergence of functional magnetic resonance imaging (fMRI) in the 1990s. Since that time, fMRI is arguably the greatest tool for understanding how the human brain operates. 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 are fundamentally different measures and follow distinct time courses, understanding their relationship is very important. However, the brain has evolved many ways to control bloodflow, thus establishing their specific connection has been a vexing problem for neuroscience. Improving our understanding of the links between the fMRI signal, local neural activity, neuromodulation, and many other factors 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 responses in the spiking responses to different modes of sensory stimulation, 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 continued two pursue a research lines attempting to understand the neural basis for spontaneous fMRI signals, functional connectivity, and their relationship to human functional brain networks. In one thread of this work, we are finalizing a follow-up study to our 2022 paper examining the relationship between spontaneous spiking at a given location and fMRI signals across the brain. This manuscript attempts to understand the role of single neurons, both excitatory projection neurons and inhibitory interneurons, in the fMRI functional connectivity networks commonly measured in the human brain. In a second thread, we have submitted a combined mouse/human study that follows up our previous collaborative paper on the quasiperiodic electrophysiological and blood oxygenation level dependent (BOLD) hemodynamic signals that arise spontaneously (Yang Y, Leopold DA, Duyn JH, and Liu X, PNAS Nexus 2024). In a third thread, we have been collaborating on a methodological project, currently under review, that proposes new ways of displaying functional activity onto the brain without relying on a hard threshold cutoff. A new area of investigation for us utilizes optogenetic stimulation of the cortex combined with fMRI readout. We are principally using this approach for mapping brain circuits, directing the light-based stimulation to different cortical sites in order to observe the downstream activation. However, we are also able to investigate the local cortical response, its relationship to spontaneous activity, and the multiple components of the hemodynamic BOLD response. The BOLD signal is a function of both blood oxygenation and flow/volume changes. Normally, sensory stimulation enters the peripheral sensory organs and propagates through multiple neural relays, which constrains the activation of cortical neurons and causes them to operate within a normal physiological range of activation, oxygen levels, and flow/volume responses. However, local excitation of the cortex allows us to systematically activate neurons to create deviations in oxygenation and hemodynamic responses that operate outside the normal range. This is allowing us to test parameters of neural activity and how they relate to both positive and negative BOLD responses.