Project 4: Dissecting the Neural and Neuromodulatory Control Mechanisms of Arterial Dynamics During Sleep

During NREM sleep, large waves of cerebrospinal fluid (CSF) flow appear in the brain. Neural slow waves precede these CSF flow waves by several seconds, suggesting that coherent neural activity could drive CSF flow by inducing large-scale neurovascular coupling. Project 4 tests the hypothesis that the spatiotemporal dynamics of neural activity regulate how CSF flows in the human brain. We optimize and integrate multiple novel MR technologies to image CSF flow in the ventricles and in perivascular spaces, with simultaneous measures of neural activity using EEG, and hemodynamic responses using fMRI.

Project 4 contributes to the overall U19 goals by determining the link between neural activity and CSF flow at multiple spatial scales. By performing whole-brain imaging in humans, we can test how both local and global neural dynamics are linked to CSF flow in the tiny perivascular spaces and in the much-larger ventricles. By interacting witth Project 2, our EEG-based measures of neural coherence will be linked to celluar-level measures of neuronal activity, with both our projects testing the link of CSF flow in the perivascular space. Our interactions with Project 3 will be critical to inform how neuromodulators shape vascular dynamics, and how neurovascular coupling is altered across sleep and wakefulness. Finally, our continuous interactions with Project 1 will be essential in order to determine which empirical measurements are needed to fully specify the model, and then update the model to make further predictions. 

Research Aims

Aim 1: Test how sensory-evoked, low-frequency neural activity is linked to CSF flow during wakefulness. 

Aim 2: Map the coupled propagation of neural, vascular, and CSF dynamics during NEM Sleep

Aim 3: Test the link between subcortical arousal circuit activity, arousal state, and CSF flow. 

Publications

2024

Gomez, D.E.P., Polimeni, J.R., Lewis, L.D. (2024). The temporal precision of fMRI responses is systematically related to anatomical location and vascular compartment. bioRxiv, https://doi.org/10.1101/2024.02.01.578428

Jacob, L., Bailes, S.M., Williams, S.D., Stringer, C., Lewis, L.D. (2024). Distributed fMRI dynamics predict distinct EEG rhythms in sleep and wakefulness. bioRxiv, https://doi.org/10.1101/2024.01.29.577429

Cicero, N.G., Fultz, N., Jeong, H., Williams, S.D., Gomez, D., Setzer, B., Warbrick, T., Jaschke, M., Gupta, R., Lev, M., Bonmassar, G.*, Lewis, L.D.* (provisionally accepted). High-quality multimodal MRI with simultaneous EEG using conductive ink and polymer-thick film nets. Journal of Neural Engineering, (in press). *Co-senior authors.

Agarwal N., Lewis, L.D., Hirschler L., Rivera Rivera L., Naganawa S., Rane Levendovszky S., Ringstad G., Klarica M., Wardlaw J., Iadecola C., Hawkes C., Carare, R., Wells, J., Bakker, E., Vartan, K., Bilston, L., Nedergaard, M., Mori, Y., Greenberg, S., Stoodley, M., Alperin, N., van Osch, M. (2024). Current understanding of the anatomy, physiology and Magnetic Resonance Imaging of neurofluids: update from the 2022 “ISMRM Imaging Neurofluids Study group” workshop in Rome. Journal of Magnetic Resonance Imaging, doi: 10.1002/jmri.28759.