Understanding how neural regions interact, both during behavioral tasks and spontaneously (e.g. at rest), is critical for studying healthy and disordered brain networks. Many studies have measured hemodynamic brain activity (fMRI), but the neural basis of hemodynamic functional connectivity remains unclear. For spontaneous functional connectivity in particular, hemodynamic measures of functional connectivity are in a low frequency (< 0.1 Hz) range while the corresponding networks found by electrophysiological measures show distinct frequency selectivity at a much faster time scale (>1 Hz). A critical conundrum for understanding spontaneous functional connectivity is: do these slow hemodynamic fluctuations arise simply as the result of the non- specific temporal smoothing that results from the slow biomechanical response of blood vessels (e.g. the hemodynamic impulse response function) or do these slow hemodynamic oscillations reflect frequency-specific neural oscillations (e.g. specific neural sub-types) or specifically low frequency neural events? Furthermore, do these spontaneous neural-vascular relationships arise from the same mechanisms as evoked brain activity or do these involve a different subset of neural interactions? Previous studies have been limited by inferring the neural underpinning of hemodynamic functional connectivity based on general spatial overlap of circuits, only examining temporal correspondence between measures, or being unable to examine the neural response across distributed circuits. We will use the approach of simultaneous multimodal recordings of electrophysiological and hemodynamic fluctuations via concurrent magnetoencephalography (MEG) and functional near infrared spectroscopy (fNIRS). In conjunction with concurrent fNIRS/fMRI/EEG, this innovative multimodal approach affords a unique opportunity to simultaneously record and co-localize neural and hemodynamic activity during interregional communication in the human brain, overcoming many limitations of previous studies. The objective in this application is to describe the correspondence between the neural and hemodynamic signals during both spontaneous and evoked tasks in two important brain networks, a circuit in the somatomotor network and one in the frontoparietal network. We propose the following two specific aims: 1. Define the regional relationship between the hemodynamic activity and the spectral properties of spontaneous and evoked electrophysiological activity. 2. Define the spatiotemporal circuit-level relationship between spontaneous and evoked hemodynamic and electrophysiological activity. The significance of this work is that its successful completion will provide a direct connection between the neural and hemodynamic underpinnings of two critical brain circuit phenomena: spontaneous brain activity and interregional communication. Determining the electrophysiological underpinnings of the brain's hemodynamic functional organization is a key step in understanding the biological basis and interpretation of hemodynamic measures of functional connectivity.
Hemodynamic measures of functional connectivity have become important and widely used tools to characterize abnormal brain communication in a host of psychiatric and neurological disorders, such as autism spectrum disorders, schizophrenia, depression, epilepsy, Alzheimer's disease, etc. However, the neural basis of the interregional correlations of the hemodynamic signal (i.e. neurovascular coupling of interregional functional connectivity) is unknown, rendering the biological interpretation of hemodynamic correlations unclear. This project is relevant to public health because it investigates the neural bases of hemodynamic functional connectivity providing a direct bridge between this measure of brain network pathology and its neural underpinnings.
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