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Xi-Nian Zuo

Publications and source records attributed to Xi-Nian Zuo.

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A Paradigm Shift in Human Neuroscience Research: Progress, Prospects, and a Proof of Concept for Population Neuroscience

Recent advances and reflections on reproducible human neuroscience, especially brain-wide association studies (BWAS) leveraging large datasets, have led to divergent and sometimes opposing views on research practices and priorities. The debates span multiple dimensions. Shifts along these axes have fractured consensus and further fragmented an already heterogeneous field of cognitive neuroscience. Here, we sketch a holistic and integrative response grounded in population neuroscience, organized around a closed-loop "design-analysis-interpretation" research cycle that aims to build consensus while bridging these divides. Our central claim is that population neuroscience offers a unique population-level vantage point for identifying general principles, characterizing inter-individual variabilities, and benchmarking intra-individual changes, thereby providing a supportive framework for small-scale, mechanism-focused studies at the individual level and allowing them to co-evolve with population-level studies. Population neuroscience is not simply about providing larger N for BWAS; its deeper goal is to accumulate a family of cross-scale priors and shared infrastructures that can support design, analysis, and interpretation of human neuroscience for decades to come. In this sense, we outline a "third-generation" view of population neuroscience that reorients the field from amassing isolated associations toward building integrative reference frameworks for future mechanistic and translational work.

q-bio.NC

Fluctuations between high- and low-modularity topology in time-resolved functional connectivity

Modularity is an important topological attribute for functional brain networks. Recent studies have reported that modularity of functional networks varies not only across individuals being related to demographics and cognitive performance, but also within individuals co-occurring with fluctuations in network properties of functional connectivity, estimated over short time intervals. However, characteristics of these time-resolved functional networks during periods of high and low modularity have remained largely unexplored. In this study we investigate spatiotemporal properties of time-resolved networks in the high and low modularity periods during rest, with a particular focus on their spatial connectivity patterns, temporal homogeneity and test-retest reliability. We show that spatial connectivity patterns of time-resolved networks in the high and low modularity periods are represented by increased and decreased dissociation of the default mode network module from task-positive network modules, respectively. We also find that the instances of time-resolved functional connectivity sampled from within the high (low) modularity period are relatively homogeneous (heterogeneous) over time, indicating that during the low modularity period the default mode network interacts with other networks in a variable manner. We confirmed that the occurrence of the high and low modularity periods varies across individuals with moderate inter-session test-retest reliability and that it is correlated with previously-reported individual differences in the modularity of functional connectivity estimated over longer timescales. Our findings illustrate how time-resolved functional networks are spatiotemporally organized during periods of high and low modularity, allowing one to trace individual differences in long-timescale modularity to the variable occurrence of network configurations at shorter timescales.

q-bio.NC

Dynamic fluctuations coincide with periods of high and low modularity in resting-state functional brain networks

We investigate the relationship of resting-state fMRI functional connectivity estimated over long periods of time with time-varying functional connectivity estimated over shorter time intervals. We show that using Pearson's correlation to estimate functional connectivity implies that the range of fluctuations of functional connections over short time scales is subject to statistical constraints imposed by their connectivity strength over longer scales. We present a method for estimating time-varying functional connectivity that is designed to mitigate this issue and allows us to identify episodes where functional connections are unexpectedly strong or weak. We apply this method to data recorded from $N=80$ participants, and show that the number of unexpectedly strong/weak connections fluctuates over time, and that these variations coincide with intermittent periods of high and low modularity in time-varying functional connectivity. We also find that during periods of relative quiescence regions associated with default mode network tend to join communities with attentional, control, and primary sensory systems. In contrast, during periods where many connections are unexpectedly strong/weak, default mode regions dissociate and form distinct modules. Finally, we go on to show that, while all functional connections can at times manifest stronger (more positively correlated) or weaker (more negatively correlated) than expected, a small number of connections, mostly within the visual and somatomotor networks, do so a disproportional number of times. Our statistical approach allows the detection of functional connections that fluctuate more or less than expected based on their long-time averages and may be of use in future studies characterizing the spatio-temporal patterns of time-varying functional connectivity

q-bio.NC

Functional brain modules reconfigure at multiple scales across the human lifespan

The human brain is a complex network of interconnected brain regions organized into functional modules with distinct roles in cognition and behavior. An important question concerns the persistence and stability of these modules over the human lifespan. Here we use graph-theoretic analysis to algorithmically uncover the brain's intrinsic modular organization across multiple spatial scales ranging from small communities comprised of only a few brain regions to large communities made up of many regions. We find that at coarse scales modules become progressively more segregated, while at finer scales segregation decreases. Module composition also exhibits scale-specific and age-dependent changes. At coarse scales, the module assignments of regions normally associated with control, default mode, attention, and visual networks are highly flexible. At fine scales the most flexible regions are associated with the default mode network. Finally, we show that, with age, some regions in the default mode network, specifically retrosplenial cortex, maintain a greater proportion of functional connections to their own module, while regions associated with somatomotor and saliency/ventral attention networks distribute their links more evenly across modules.

q-bio.NC

Generative models of the human connectome

The human connectome represents a network map of the brain's wiring diagram and the pattern into which its connections are organized is thought to play an important role in cognitive function. The generative rules that shape the topology of the human connectome remain incompletely understood. Earlier work in model organisms has suggested that wiring rules based on geometric relationships (distance) can account for many but likely not all topological features. Here we systematically explore a family of generative models of the human connectome that yield synthetic networks designed according to different wiring rules combining geometric and a broad range of topological factors. We find that a combination of geometric constraints with a homophilic attachment mechanism can create synthetic networks that closely match many topological characteristics of individual human connectomes, including features that were not included in the optimization of the generative model itself. We use these models to investigate a lifespan dataset and show that, with age, the model parameters undergo progressive changes, suggesting a rebalancing of the generative factors underlying the connectome across the lifespan.

q-bio.NC