The human connectome is the set of physical pathways linking brain regions to one another. Empirical and in silico studies have demonstrated that the structure of this network helps shape patterns of functional coupling between brain regions. To better understand this link between structure and function, a growing number of studies have derived geometric, dynamic, and topological predictors from structural connectivity in order to make predictions about correlation structure. These studies, however, have typically focused on global (whole-brain) predictions using a restricted set of predictors. Here, we investigate a wide range of predictors and shift focus onto predictions of local (regional) patterns of functional coupling. We show that, globally, no individual predictor performs well and, that even the best predictors are largely driven by their ability to predict functional coupling between directly connected regions. We then use the same predictors to make predictions of local coupling and find marked improvement. Notably, the most predictable local FC is linked to sensorimotor regions, which are best predicted by measures based on topological similarity, mean first passage times of random walkers, and the brain’s embedding in Euclidean space. We then show that by combining the predictive power of more than one predictor using multi-linear models, we can further improve local predictions. Finally, we investigate how global and local structure-function coupling changes across the human lifespan. We find that, globally, the magnitude of coupling decreases with biological age, which is paralleled by an increase in the number of multi-step pathways. We also show that, locally, structure-function coupling is preserved in higher order cognitive systems, but preferentially decreases with age in sensorimotor systems. Our results illuminate the heterogeneous landscape of structure-function coupling across the cerebral cortex and help clarify its changes with age.

/pdf/local-structure-function-relationships-in-human-brain-1ujwpt2ba1.pdf

Local structure-function relationships in human brain networks across the human lifespan

Abstract Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition. 

/pdf/genetic-and-phylogenetic-uncoupling-of-structure-and-eah5q7wo.pdf

Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex

Abstract A growing number of studies have used stylized network models of communication to predict brain function from structure. Most have focused on a small set of models applied globally. Here, we compare a large number of models at both global and regional levels. We find that globally most predictors perform poorly. At the regional level, performance improves but heterogeneously, both in terms of variance explained and the optimal model. Next, we expose synergies among predictors by using pairs to jointly predict FC. Finally, we assess age-related differences in global and regional coupling across the human lifespan. We find global decreases in the magnitude of structure-function coupling with age. We find that these decreases are driven by reduced coupling in sensorimotor regions, while higher-order cognitive systems preserve local coupling with age. Our results describe patterns of structure-function coupling across the cortex and how this may change with age. 

https://www.nature.com/articles/s41467-022-29770-y.pdf

Local structure-function relationships in human brain networks across the lifespan

Where the genome meets the connectome: Understanding how genes shape human brain connectivity.

The relationship between structural and functional connectivity in the brain is a key question in systems neuroscience. Modern accounts assume a single global structure-function relationship that persists over time. Here we study structure-function coupling from a dynamic perspective, and show that it is regionally heterogeneous. We use a temporal unwrapping procedure to identify moment-to-moment co-fluctuations in neural activity, and reconstruct time-resolved structure-function coupling patterns. We find that patterns of dynamic structure-function coupling are region-specific. We observe stable coupling in unimodal and transmodal cortex, and dynamic coupling in intermediate regions, particularly in insular cortex (salience network) and frontal eye fields (dorsal attention network). Finally, we show that the variability of a region's structure-function coupling is related to the distribution of its connection lengths. Collectively, our findings provide a way to study structure-function relationships from a dynamic perspective. 

/pdf/time-resolved-structure-function-coupling-in-brain-networks-77avzh48.pdf

Time-resolved structure-function coupling in brain networks

White matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors. The relationship between the human structural and functional connectome is still not well established. Here the authors show the interindividual variability that exists in regional coupling of structural and functional connectivity across the brain, and that this is heritable.

/pdf/heritability-and-interindividual-variability-of-regional-1phak32evw.pdf

Heritability and interindividual variability of regional structure-function coupling.

Functional MRI (fMRI) is a powerful technique that has allowed us to characterize visual cortex responses to stimuli, yet such experiments are by nature constructed based on a priori hypotheses, limited to the set of images presented to the individual while they are in the scanner, are subject to noise in the observed brain responses, and may vary widely across individuals. In this work, we propose a novel computational strategy, which we call NeuroGen, to overcome these limitations and develop a powerful tool for human vision neuroscience discovery. NeuroGen combines an fMRI-trained neural encoding model of human vision with a deep generative network to synthesize images predicted to achieve a target pattern of macro-scale brain activation. We demonstrate that the reduction of noise that the encoding model provides, coupled with the generative network's ability to produce images of high fidelity, results in a robust discovery architecture for visual neuroscience. By using only a small number of synthetic images created by NeuroGen, we demonstrate that we can detect and amplify differences in regional and individual human brain response patterns to visual stimuli. We then verify that these discoveries are reflected in the several thousand observed image responses measured with fMRI. We further demonstrate that NeuroGen can create synthetic images predicted to achieve regional response patterns not achievable by the best-matching natural images. The NeuroGen framework extends the utility of brain encoding models and opens up a new avenue for exploring, and possibly precisely controlling, the human visual system.

NeuroGen: activation optimized image synthesis for discovery neuroscience.

Estimated connectivity networks outperform observed connectivity networks when classifying people with multiple sclerosis into disability groups.

Large scale white matter brain connections quantified via the structural connectome (SC) act as the backbone for the flow of functional activation, which can be represented via the functional connectome (FC). Many studies have used statistical analysis or computational modeling techniques to relate SC and FC at a global, whole-brain level. However, relatively few studies have investigated the relationship between individual cortical and subcortical regions9 structural and functional connectivity profiles, here called SC-FC coupling, or how this SC-FC coupling may be heritable or related to age, sex and cognitive abilities. Here, we quantify regional SC-FC coupling in a large group of healthy young adults (22 to 37 years) using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project. We find that while regional SC-FC coupling strengths vary widely across cortical, subcortical and cerebellar regions, they were strongest in highly structurally connected visual and subcortical areas. Additionally, depending on the region, SC-FC coupling varied across sexes and with age and composite cognitive scores. Specifically, SC-FC coupling in the cerebellum tended to decrease with age while coupling in medial fronto-orbital areas tended to increase with age. Males had stronger coupling in many regions, particularly in the right orbito-frontal region and areas in the ventral attention and default mode networks, while females had higher coupling strength in right hippocampus. Furthermore, increased SC-FC coupling in the right insula and decreased coupling in bilateral middle cingulate and supplementary motor areas was associated with higher composite cognitive scores. Finally, we found SC-FC coupling to be highly heritable, particularly in higher order default mode, dorsal/ventral attention and fronto-parietal networks. Taken together, these results suggest regional structure-function coupling in young adults varies with age, is generally stronger in males, is associated with composite cognitive scores and is highly heritable.

https://www.biorxiv.org/content/biorxiv/early/2020/12/11/2020.12.09.417725.full.pdf

Regional structural-functional connectome coupling is heritable and associated with age, sex and cognition in adults

Quantifying population heterogeneity in brain stimuli-response mapping may allow insight into variability in bottom-up neural systems that can in turn be related to individual's behavior or pathological state. Encoding models that predict brain responses to stimuli are one way to capture this relationship. However, they generally need a large amount of fMRI data to achieve optimal accuracy. Here, we propose an ensemble approach to create encoding models for novel individuals with relatively little data by modeling each subject's predicted response vector as a linear combination of the other subjects' predicted response vectors. We show that these ensemble encoding models trained with hundreds of image-response pairs, achieve accuracy not different from models trained on 20,000 image-response pairs. Importantly, the ensemble encoding models preserve patterns of inter-individual differences in the image-response relationship. We also show the proposed approach is robust against domain shift by validating on data with a different scanner and experimental setup. Additionally, we show that the ensemble encoding models are able to discover the inter-individual differences in various face areas' responses to images of animal vs human faces using a recently developed NeuroGen framework. Our approach shows the potential to use existing densely-sampled data, i.e. large amounts of data collected from a single individual, to efficiently create accurate, personalized encoding models and, subsequently, personalized optimal synthetic images for new individuals scanned under different experimental conditions. 

/pdf/personalized-visual-encoding-model-construction-with-small-3axl9por.pdf

Zijin Gu

Papers

Heritability and interindividual variability of regional structure-function coupling.

NeuroGen: activation optimized image synthesis for discovery neuroscience.

Estimated connectivity networks outperform observed connectivity networks when classifying people with multiple sclerosis into disability groups.

Regional structural-functional connectome coupling is heritable and associated with age, sex and cognition in adults

Personalized visual encoding model construction with small data