Lindsey Brier

Program: Neurosciences

Current advisor: Joseph P. Culver, PhD

Undergraduate university: University of Houston

Research summary
Accurate mapping of brain networks has been a goal spanning multiple decades of research in the fMRI world in order to understand the overwhelmingly complex human brain. While advances in this realm have led to clinically relevant biomarkers of disease as well as a fundamental understanding of systems neuroscience, similar developments in the mouse brain, which is frequently studied to understand human conditions, are lagging. This limitation on translational research is due to the limited spatial resolution of fMRI in the comparatively small mouse brain. To this end, we use high-resolution wide-field optical imaging to map cortical mouse brain circuits in a cell-specific manner. There are numerous benefits to this approach in mice, such as the ability to monitor neural specific calcium dynamics (up to 15Hz) by using genetically encoded calcium indicators (GECI’s, e.g. GCaMP6f), and the ability to control genetic and environmental variables in ways that are not possible in human studies. Mathematical techniques popular in the human fMRI literature such as machine learning and functional connectivity (FC) metrics are easily translatable to the optical imaging data, allowing for direct comparisons between mice and humans. Most notably, we have used FC analysis across multiple modulated brain states (e.g. sleep, anesthesia) using this optical approach in mice to elucidate key sleep physiology by tracking neural specific, fast calcium transients that are inaccessible with fMRI. In other realms, clinically novel therapeutic approaches, such as hypoxic conditioning, have shown unique functional imaging correlates indicating a promising approach to prevent delayed cerebral ischemia in a subarachnoid hemorrhage mouse model. In conclusion, this optical approach allows for unprecedented translational models in order to better understand how to sustain healthy brain networks and how they deteriorate in disease.ease.

Graduate publications
Rahn RM, Brier LM, Bice AR, Reisman MD, Dougherty JD, Culver J. 2022 Functional Connectivity of the Developing Mouse Cortex. Cereb Cortex, 32(8):1755-68.

Zhang X, Landsness EC, Chen W, Miao H, Tang M, Brier LM, Culver JP, Lee JM, Anastasio MA. 2022 Automated sleep state classification of wide-field calcium imaging data via multiplex visibility graphs and deep learning. J Neurosci Methods, 366():109421.

Clarke JV, Brier LM, Rahn RM, Diwan D, Yuan JY, Bice AR, Imai SI, Vellimana AK, Culver JP, Zipfel GJ. 2022 SIRT1 mediates hypoxic postconditioning- and resveratrol-induced protection against functional connectivity deficits after subarachnoid hemorrhage. J Cereb Blood Flow Metab, 42(7):1210-23.

Brier LM, Zhang X, Bice AR, Gaines SH, Landsness EC, Lee JM, Anastasio MA, Culver JP. 2021 A Multivariate Functional Connectivity Approach to Mapping Brain Networks and Imputing Neural Activity in Mice. Cereb Cortex, epub ahead of print():hbab282.

Spears LD, Adak S, Dong G, Wei X, Spyropoulos G, Zhang Q, Yin L, Feng C, Hu D, Lodhi IJ, Hsu FF, Rajagopal R, Noguchi KK, Halabi CM, Brier L, Bice AR, Lananna BV, Musiek ES, Avraham O, Cavalli V, Holth JK, Holtzman DM, Wozniak DF, Culver JP, Semenkovich CF. 2021 Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration. J Lipid Res, 62():100079.

Smith SE, Chen X, Brier LM, Bumstead JR, Rensing NR, Ringel AE, Shin H, Oldenborg A, Crowley JR, Bice AR, Dikranian K, Ippolito JE, Haigis MC, Papouin T, Zhao G, Wong M, Culver JP, Bonni A. 2020 Astrocyte deletion of α2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway. Nat Commun, 11(1):6164.

Brier LM, Landsness EC, Snyder AZ, Wright PW, Baxter GA, Bauer AQ, Lee JM, Culver JP. 2019 Separability of calcium slow waves and functional connectivity during wake, sleep, and anesthesia. Neurophotonics, 6(3):035002.

Rahn RM, Maloney SE, Brier LM, Dougherty JD, Culver JP. 2019 Maternal Fluoxetine Exposure Alters Cortical Hemodynamic and Calcium Response of Offspring to Somatosensory Stimuli. eNeuro, 6(6):pii: ENEURO.0238-19.

Friedman RZ, Gish SR, Brown H, Brier L, Howard N, Doering TL, Brent MR. 2018 Unintended Side Effects of Transformation Are Very Rare in Cryptococcus neoformans. G3 (Bethesda), 8(3):815-822.

Milchenko M, Snyder AZ, Campbell MC, Dowling JL, Rich KM, Brier LM, Perlmutter JS, Norris SA. 2018 ESM-CT: a precise method for localization of DBS electrodes in CT images. J Neurosci Methods, 308():366-376.

Brier LM, Landsness EC, Mensen A, Wright PW, Baxter G, Snyder AZ, Bauer AQ, Lee JM, Culver JP. (2018) The Relationship between the Slow Oscillation and Underlying Resting State Cortical Activity during Anesthesia and NREM Sleep. Optics and the Brain, Hollywood, FL, Abstract.

Brier LM, Landsness EC, Mensen A, Wright PW, Baxter G, Bauer AQ, Lee JM, Culver JP. (2017) Mesoscopic Cortical Calcium Slow Waves During Wakefulness, Sleep, and Anesthesia. Society for Neuroscience, Washington, DC, Abstract.

Brier LM, Landsness EC, Wright P, Bauer AQ, Baxter G, Lee J, Culver JP. (2017) Mesoscopic cortical calcium dynamics during wakefulness, natural sleep, and anesthesia. Optical Society of America: Optics and the Brain, San Diego, CA, Abstract.

Wright PW, Brier LM, Bauer AQ, Baxter GA, Kraft AW, Reisman MD, Bice AR, Snyder A, Lee JM, Culver JP. 2017 Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice. PLoS ONE, 12(10):e0185759.