Annie G. Bryant

Hi! I’m Annie, a third-year PhD Candidate working with Dr Ben Fulcher in the Dynamics and Neural Systems Lab at The University of Sydney.

For my thesis research, I’m interested in the nuanced changes to neural dynamics that characterize a given disorder, with a particular focus on Alzheimer’s disease. I integrate multimodal neuroimaging data with highly comparative time-series analysis to better understand how Alzheimer’s disease pathology disrupts functional neural architecture, from individual cells to distributed networks of brain regions.

Before moving to Sydney, I lived in Boston while studying at Northeastern University and researching the relationship between tau pathology and vascular function under the supervision of Dr. Rachel Bennett at the MassGeneral Institute for Neurodegenerative Disease.

To read more about my current and past research projects, check out my Projects page.

Outside of the lab, you can find me biking, hiking, hammocking, embroidering, roller skating, or FaceTiming with Mojo, my cat back home.

news

Jan 15, 2024	My first two years as a PhD candidate have culminated in my first preprint with the group, now up on biorXiv!
Sep 29, 2023	Lab group repped at the Complex Systems Emerging Aspirations 2023 Symposium
Jul 21, 2023	H4ck3d away at the 2023 OHBM BrainHack in Montreal
Jun 15, 2023	Presented at the second Fudan-Cambridge-Sydney Young Scholars Symposium
May 31, 2023	Attended the Australian Dementia Research Forum (ADRF) 2023 as a poster presenter

selected publications

2024

bioRxiv

Extracting interpretable signatures of whole-brain dynamics through systematic comparison

Annie G. Bryant, Kevin Aquino, Linden Parkes, Alex Fornito, and Ben D. Fulcher

bioRxiv, 2024

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Despite a rich and interdisciplinary literature on time-series analysis, the brain’s complex distributed dynamics are typically quantified using only a limited set of manually selected representations and statistics. This leaves open the possibility that alternative dynamical properties may outperform those reported for a given application. Here we address this limitation by introducing a systematic procedure to compare diverse, interpretable features of functional magnetic resonance imaging (fMRI) data, drawn from comprehensive algorithmic libraries to capture both dynamical properties of individual brain regions (intra-regional activity) and patterns of statistical dependence between regions (inter-regional functional coupling). We apply our data-driven approach to investigate alterations to dynamical structures in resting-state fMRI in participants with schizophrenia (SCZ), bipolar 1 disorder (BP), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). Our findings broadly support the use of linear time-series analysis techniques for fMRI-based case–control analysis, while also identifying novel informative dynamical structures that have previously received less attention. While some simple statistical representations of fMRI dynamics perform surprisingly well (e.g., properties within a single brain region), we found performance improvements through combining intra-regional properties with inter-regional coupling—consistent with distributed, multifaceted changes to fMRI dynamics in neuropsychiatric disorders. The data-driven approach here enables the systematic identification and interpretation of disorder-specific dynamical signatures, with applicability beyond neuroimaging to diverse scientific problems involving complex time-varying systems.

2023

Nat Comp Sci

Unifying pairwise interactions in complex dynamics

Oliver M Cliff, Annie G Bryant, Joseph T Lizier, Naotsugu Tsuchiya, and Ben D Fulcher

Nature Computational Science, 2023

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Scientists have developed hundreds of techniques to measure the interactions between pairs of processes in complex systems, but these computational methods—from contemporaneous correlation coefficients to causal inference methods—define and formulate interactions differently, using distinct quantitative theories that remain largely disconnected. Here we introduce a large assembled library of 237 statistics of pairwise interactions, and assess their behavior on 1,053 multivariate time series from a wide range of real-world and model-generated systems. Our analysis highlights commonalities between disparate mathematical formulations of interactions, providing a unified picture of a rich interdisciplinary literature. Using three real-world case studies, we then show that simultaneously leveraging diverse methods can uncover those most suitable for addressing a given problem, facilitating interpretable understanding of the quantitative formulation of pairwise dependencies that drive successful performance. Our results and accompanying software enable comprehensive analysis of time-series interactions by drawing on decades of diverse methodological contributions.
J Neurosci

Endothelial cells are heterogeneous in different brain regions and are dramatically altered in Alzheimer’s disease

Annie Bryant, Zhaozhi Li, Rojashree Jayakumar, Alberto Serrano-Pozo, Benjamin Woost, Miwei Hu, Maya E Woodbury, Astrid Wachter, Gen Lin, Taekyung Kwon, Robert V Talanian, Knut Biber, Eric H Karran, Bradley T Hyman, Sudeshna Das, and Rachel Bennett

Journal of Neuroscience, 2023

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Vascular endothelial cells play an important role in maintaining brain health, but their contribution to Alzheimer’s disease (AD) is obscured by limited understanding of the cellular heterogeneity in normal aged brain and in disease. To address this, we performed single nucleus RNAseq on tissue from 32 human AD and non-AD donors (19 female, 13 male) each with five cortical regions: entorhinal cortex, inferior temporal gyrus, prefrontal cortex, visual association cortex and primary visual cortex. Analysis of 51,586 endothelial cells revealed unique gene expression patterns across the five regions in non-AD donors. Alzheimer’s brain endothelial cells were characterized by upregulated protein folding genes and distinct transcriptomic differences in response to amyloid beta plaques and cerebral amyloid angiopathy (CAA). This dataset demonstrates previously unrecognized regional heterogeneity in the endothelial cell transcriptome in both aged non-AD and AD brain.

2021

Curr Alz Res

Heterogeneity of tau deposition and microvascular involvement in MCI and AD

Annie G Bryant, Mary K Manhard, David H Salat, Bruce R Rosen, Bradley T Hyman, Keith A Johnson, Susie Huang, Rachel E Bennett, and Yi-Fen Yen

Current Alzheimer Research, 2021

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Background: Reduced cerebrovascular function and accumulation of tau pathology are key components of cognitive decline in Alzheimer’s disease (AD). Recent multimodal neuroimaging studies show a correlation between cortical tau accumulation and reduced cerebral perfusion. However, animal models predict that tau exerts capillary-level changes that may not be fully captured by standard imaging protocols. Objective: Using newly-developed magnetic resonance imaging (MRI) technology to measure capillary- specific perfusion parameters, we examined a series of mild cognitive impairment (MCI) and AD patients with tau positron emission tomography (PET) to observe whole-brain capillary perfusion alterations and their association with tau deposition. Methods: Seven subjects with MCI or AD received Flortaucipir PET to measure tau deposition and spin-echo dynamic susceptibility contrast (SE-DSC) MRI to measure microvascular perfusion (<10μm radius vessels). Gradient-echo (GE) DSC and pseudocontinuous arterial spin labeling (PCASL) MRI were also acquired to assess macrovascular perfusion. Tau PET, microvascular perfusion, and cortical thickness maps were visually inspected in volumetric slices and on cortical surface projections. Results: High tau PET signal was generally observed in the lateral temporal and parietal cortices, with uptake in the occipital cortex in one subject. Global blood flow measured by PCASL was reduced with increasing tau burden, which was consistent with previous studies. Tau accumulation was spatially associated with variable patterns of microvascular cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in the cortex and with increased capillary transit heterogeneity (CTH) in adjacent periventricular white matter, independent of amyloid-β status. Conclusion: Although macrovascular perfusion generally correlated with tau deposition at the whole-cortex level, regional changes in microvascular perfusion were not uniformly associated with either tau pathology or cortical atrophy. This work highlights the heterogeneity of AD-related brain changes and the challenges of implementing therapeutic interventions to improve cerebrovascular function.

2020

Front Neurol

Cerebrovascular senescence is associated with tau pathology in Alzheimer’s disease

Annie G Bryant, Miwei Hu, Becky C Carlyle, Steven E Arnold, Matthew P Frosch, Sudeshna Das, Bradley T Hyman, and Rachel E Bennett

Frontiers in Neurology, 2020

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Alzheimer’s Disease (AD) is associated with neuropathological changes, including aggregation of tau neurofibrillary tangles (NFTs) and amyloid-beta plaques. Mounting evidence indicates that vascular dysfunction also plays a key role in the pathogenesis and progression of AD, in part through endothelial dysfunction. Based on findings in animal models that tau pathology induces vascular abnormalities and cellular senescence, we hypothesized that tau pathology in the human AD brain leads to vascular senescence. To explore this hypothesis, we isolated intact microvessels from the dorsolateral prefrontal cortex (PFC, BA9) from 16 subjects with advanced Braak stages (Braak V/VI, B3) and 12 control subjects (Braak 0/I/II, B1), and quantified expression of 42 genes associated with senescence, cell adhesion, and various endothelial cell functions. Genes associated with endothelial senescence and leukocyte adhesion, including SERPINE1 (PAI-1), CXCL8 (IL8), CXCL1, CXCL2, ICAM-2, and TIE1, were significantly upregulated in B3 microvessels after adjusting for sex and cerebrovascular pathology. In particular, the senescence-associated secretory phenotype genes SERPINE1 and CXCL8 were upregulated by more than 2-fold in B3 microvessels after adjusting for sex, cerebrovascular pathology, and age at death. Protein quantification data from longitudinal plasma samples for a subset of 13 (n = 9 B3, n = 4 B1) subjects showed no significant differences in plasma senescence or adhesion-associated protein levels, suggesting that these changes were not associated with systemic vascular alterations. Future investigations of senescence biomarkers in both the peripheral and cortical vasculature could further elucidate links between tau pathology and vascular changes in human AD.