Study of the brains functional anatomy has seen rapid progress in recent years, in part because of the availability of large databases of fMRI data obtained from human subjects at rest. However, the dependence of spontaneous brain activity patterns on physiological and behavioral conditions, as recently revealed by researchers in our lab and other labs, complicates interpretation. For this reason, our lab has continued to investigate the sources contributing to and the factors affecting spontaneous brain activity. Over the last year, this has proceeded along two separate avenues, involving the analysis of existing data, as well as the initiation of novel experiments. In a first project, led by Catie Chang, we followed up on a previous finding in macaque that behavioral arousal changes, as measured from eyelid position, are associated with a prototypical fMRI activity pattern. We have started a concurrent EEG-fMRI experiment in humans to relate the occurrence of the pattern to arousal state, as measured from the EEG signal. If this relationship is confirmed, this would allow identifying and separating arousal state dependent effects on brain activity from other types of spontaneous brain activity, thereby improving the charting of brain functional connectivity. Several test scans have been performed and data acquisition on six normal volunteers has been completed. A second project, led by Dante Picchioni, aims at investigating spontaneous brain activity across the broad spectrum of arousal states occurring during natural sleep. EEG, fMRI, and behavioral measures of arousal state are being acquired with the goals of better understanding the nature of spontaneous brain activity, its dependence on arousal state, an potential differences within classical, EEG-defined sleep states. Auditory threshold stimuli are being used to gauge sleep depth independently of the EEG. Overnight experiments are being performed that are preceded with an adaptation session on the prior night. We have just completed a pilot study aimed at determining effect sizes of fMRI signal changes versus arousal threshold. Twelve successful experiments have been performed and the elaborate data analysis has started. The latter involves various data correction procedures to free the fMRI and EEG data from artifactual signals. It is anticipated that based on preliminary analysis, to be completed in late 2017, a full study protocol will be submitted to the IRB. In parallel with these projects, we have continued to investigate basic MRI contrast mechanisms in order to be better able to study the effects of neurological disease on white matter myelin content. In the past, much of this work has been performed in collaboration with the Neuroimmunology branch (NIB), and this joint development work is continuing. In 2017, we performed dedicated experiments to study the effect of immobile protons in myelin on the NMR properties of water protons that are responsible for the MRI signal. From these experiments, we determined the spectral charateristics of these protons, as well as the exchange rates of water protons across the myelin sheath. Separately, we studied the relative utility of magnetic susceptibility contrast and the exchange of immobile protons and water protons to quantify tissue myelin content. It was found that the latter is more precise.
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