Several recent studies have optimized deep neural networks to learn high-dimensional relationships linking structural and functional connectivity across the human connectome. However, the extent to which these models recapitulate individual-specific characteristics of resting-state functional brain networks remains unclear. A core concern relates to whether current individual predictions outperform simple benchmarks such as group averages and null conditions. Here, we consider two measures to statistically evaluate whether functional connectivity predictions capture individual effects. We revisit our previously published functional connectivity predictions for 1,000 healthy adults and provide multiple lines of evidence supporting that our predictions successfully capture subtle individual-specific variation in connectivity. While predicted individual effects are statistically significant and outperform several benchmarks, we find that effect sizes are small (i.e., 8%–11% improvement relative to group-average benchmarks). As such, initial expectations about individual prediction performance expressed by us and others may require moderation. We conclude that individual predictions can significantly outperform appropriate benchmark conditions and we provide several recommendations for future studies in this area. Future studies should statistically assess the individual prediction performance of their models using one of the measures and benchmarks provided here. Author Summary Functional and structural brain networks share considerable overlap in network architecture. However, it remains debated whether deep neural networks can be trained to predict an individual's functional brain network from their structural connectome. We demonstrate that individual variability in functional brain connectivity can be successfully predicted from an individual's connectome, although prediction performance is modest when benchmarked against appropriate null models. We provide recommendations for future studies aiming to evaluate such predictions, specifically considering the impact of Riemann geometry, adjustments for cross-validation induced dependence and standardization. Accurate prediction models will enable extrapolation of functional networks for individuals without empirically acquired functional MRI data or noisy data. They may also facilitate digital simulations of the potential functional consequences arising from pathological changes in the connectome.

Author Summary Brain networks identified by functional connectivity (FC) have preserved architectures from rest to task and across task demands. Higher similarity, implying more efficient network reconfiguration, was associated with better cognition and task performance in young adults. To examine how it may be influenced by aging, we compared whole-brain and network-level FC similarities between resting-state and spatial working memory fMRI in young and older adults. At whole-brain level and higher order cognitive networks, older adults evidenced less efficient network reconfiguration from rest to task than young adults. Importantly, more efficient reconfiguration was associated with better accuracy. This relationship relied more on internetwork connections in older adults. Despite reduced neural resources compared to young, maintaining efficient network updating still contributes to better cognition at older age. Abstract Functional brain networks have preserved architectures in rest and task; nevertheless, previous work consistently demonstrated task-related brain functional reorganization. Efficient rest-to-task functional network reconfiguration is associated with better cognition in young adults. However, aging and cognitive load effects, as well as contributions of intra- and internetwork reconfiguration, remain unclear. We assessed age-related and load-dependent effects on global and network-specific functional reconfiguration between rest and a spatial working memory (SWM) task in young and older adults, then investigated associations between functional reconfiguration and SWM across loads and age groups. Overall, global and network-level functional reconfiguration between rest and task increased with age and load. Importantly, more efficient functional reconfiguration associated with better performance across age groups. However, older adults relied more on internetwork reconfiguration of higher cognitive and task-relevant networks. These reflect the consistent importance of efficient network updating despite recruitment of additional functional networks to offset reduction in neural resources and a change in brain functional topology in older adults. Our findings generalize the association between efficient functional reconfiguration and cognition to aging and demonstrate distinct brain functional reconfiguration patterns associated with SWM in aging, highlighting the importance of combining rest and task measures to study aging cognition.

Author Summary Here we used a thermodynamics-inspired, deep learning based Temporal Evolution NETwork (TENET) framework to assess the asymmetry in the flow of events, ‘arrow of time’, in human brain signals. This was applied to large-scale HCP neuroimaging data which showed significant changes between the hierarchy of orchestration for the resting state and seven different cognitive tasks. Similarly, the hierarchy of the resting state is significantly different in health compared to neuropsychiatric disorders. This framework provided new insights into the orchestrating of brain dynamics in different brain states. Abstract A promising idea in human cognitive neuroscience is that the default mode network (DMN) is responsible for coordinating the recruitment and scheduling of networks for computing and solving task-specific cognitive problems. This is supported by evidence showing that the physical and functional distance of DMN regions is maximally removed from sensorimotor regions containing environment-driven neural activity directly linked to perception and action, which would allow the DMN to orchestrate complex cognition from the top of the hierarchy. However, discovering the functional hierarchy of brain dynamics requires finding the best way to measure interactions between brain regions. In contrast to previous methods measuring the hierarchical flow of information using, for example, transfer entropy, here we used a thermodynamics-inspired, deep learning based Temporal Evolution NETwork (TENET) framework to assess the asymmetry in the flow of events, ‘arrow of time’, in human brain signals. This provides an alternative way of quantifying hierarchy, given that the arrow of time measures the directionality of information flow that leads to a breaking of the balance of the underlying hierarchy. In turn, the arrow of time is a measure of nonreversibility and thus nonequilibrium in brain dynamics. When applied to large-scale Human Connectome Project (HCP) neuroimaging data from close to a thousand participants, the TENET framework suggests that the DMN plays a significant role in orchestrating the hierarchy, that is, levels of nonreversibility, which changes between the resting state and when performing seven different cognitive tasks. Furthermore, this quantification of the hierarchy of the resting state is significantly different in health compared to neuropsychiatric disorders. Overall, the present thermodynamics-based machine-learning framework provides vital new insights into the fundamental tenets of brain dynamics for orchestrating the interactions between cognition and brain in complex environments.

Progress in scientific disciplines is accompanied by standardization of terminology. Network neuroscience, at the level of macroscale organization of the brain, is beginning to confront the challenges associated with developing a taxonomy of its fundamental explanatory constructs. The Workgroup for HArmonized Taxonomy of NETworks (WHATNET) was formed in 2020 as an Organization for Human Brain Mapping (OHBM)–endorsed best practices committee to provide recommendations on points of consensus, identify open questions, and highlight areas of ongoing debate in the service of moving the field toward standardized reporting of network neuroscience results. The committee conducted a survey to catalog current practices in large-scale brain network nomenclature. A few well-known network names (e.g., default mode network) dominated responses to the survey, and a number of illuminating points of disagreement emerged. We summarize survey results and provide initial considerations and recommendations from the workgroup. This perspective piece includes a selective review of challenges to this enterprise, including (1) network scale, resolution, and hierarchies; (2) interindividual variability of networks; (3) dynamics and nonstationarity of networks; (4) consideration of network affiliations of subcortical structures; and (5) consideration of multimodal information. We close with minimal reporting guidelines for the cognitive and network neuroscience communities to adopt.

Large variability exists across brain regions in health and disease, considering their cellular and molecular composition, connectivity, and function. Large-scale whole-brain models comprising coupled brain regions provide insights into the underlying dynamics that shape complex patterns of spontaneous brain activity. In particular, biophysically grounded mean-field whole-brain models in the asynchronous regime were used to demonstrate the dynamical consequences of including regional variability. Nevertheless, the role of heterogeneities when brain dynamics are supported by synchronous oscillating state, which is a ubiquitous phenomenon in brain, remains poorly understood. Here, we implemented two models capable of presenting oscillatory behavior with different levels of abstraction: a phenomenological Stuart–Landau model and an exact mean-field model. The fit of these models informed by structural- to functional-weighted MRI signal (T1w/T2w) allowed us to explore the implication of the inclusion of heterogeneities for modeling resting-state fMRI recordings from healthy participants. We found that disease-specific regional functional heterogeneity imposed dynamical consequences within the oscillatory regime in fMRI recordings from neurodegeneration with specific impacts on brain atrophy/structure (Alzheimer’s patients). Overall, we found that models with oscillations perform better when structural and functional regional heterogeneities are considered, showing that phenomenological and biophysical models behave similarly at the brink of the Hopf bifurcation. Author Summary Significant progress has been made in understanding the effects of regional heterogeneity on whole-brain dynamics. With imaging technologies, the number of high-resolution reference maps of brain structure and function has been increased, and whole-brain computational models have provided a suitable avenue to investigate the mechanisms supporting the relations between these maps and whole-brain dynamics. Here, we investigate the role of the heterogeneities when synchronous behavior is present in brain dynamics, which we could represent by models capable of oscillating in the presence of a Hopf bifurcation. We found that models with oscillations more faithfully reproduce empirical properties when structural and functional regional heterogeneities are considered, showing that both phenomenological and biophysical models behave similarly at the brink of the Hopf bifurcation.