Functional magnetic resonance imaging (fMRI) may be the technological advance that has had the greatest impact on our understanding how the human 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 operate by entirely different principles, pinpointing their specific connection has been elusive and seems to depend on many 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 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 followed up on two studies related to the neural basis of the fMRI signal. In one collaborative study, we investigated a new aspect of the brain-wide spiking dynamics underlying the quasiperiodic BOLD signals known to synchronously affect the brain during sleep (Yang Y, Leopold DA, Duyn JH, and Liu X, PNAS Nexus 2024). That study, based on mouse electrophysiology from the Allen brain institute database, found that the large-scale brain-wide spiking patterns previously shown to link to fMRI activity (Liu X, Leopold DA, Yang Y, PNAS 2021), are strongly coordinated with hippocampal replay activity during rest. These findings, together with additional collaborative work currently underway, suggest that the off-line physiology of the brain is highly coordinated, affecting the firing of approximately 70% of forebrain neurons and involving a direct interaction between the cortex and hippocampus. In another collaborative follow-up study, we examined the consequences of the basal forebrain input to the cortex during rest. We previously demonstrated through combined inactivation and fMRI that broadcast projections from this structure strongly shape the global signal component of the spontaneous fMRI activity across the cortex (Turchi J et al, Neuron 2018). In a recent follow-up study, we found quantitative evidence that the cholinergic input to the cortex coming from the basal forebrain acts as a stabilizing mechanism for brain states (Taylor NL et al , Cell Reports, 2024). This finding helps for understanding the connection between temporal fluctuations in the resting brain and the slower switching between distinct states of arousal. As such, it is relevant for understanding the mechanism of fMRI functional connectivity in health and disease.