Recent neuroimaging studies demonstrated that task-evoked functional connectivity (FC) may better predict individual traits than resting-state FC. However, the prediction properties of task-evoked effective connectivity (EC) remain unexplored. We investigated this by predicting individual reaction time (RT) performance in the stimulus-response compatibility task and age, using intrinsic EC (I-EC; calculated at baseline) and task-modulated EC (M-EC; induced by experimental conditions) with dynamic causal modeling (DCM) across various data processing conditions, including different general linear model (GLM) designs, Bayesian model reduction, and different cross-validation schemes and prediction models. We report evident differences in predicting RT and age between I-EC and M-EC, as well as between event-related and block-based GLM and DCM designs. M-EC outperformed both I-EC and task-evoked FC in RT prediction, while all types of connectivity performed similarly for age. Event-related GLM and DCM designs performed better than block-based designs. Our findings suggest that task-evoked I-EC and M-EC may capture different phenotypic attributes, with performance influenced by data processing and modeling choices, particularly the GLM-DCM design. This evaluation of methods for behavior prediction from brain EC may contribute to a meta-scientific understanding of how data processing and modeling frameworks influence neuroimaging-based predictions, offering insights for improving their robustness and efficacy. Author Summary We investigated how brain task-evoked effective connectivity (EC) can predict individual differences in behavior and age. We examined two types of EC: intrinsic EC (calculated at baseline) and task-modulated EC (induced by experimental conditions) calculated by dynamic causal modeling across various data processing conditions. We found that the task-modulated EC outperformed intrinsic EC in predicting reaction time measured during a stimulus-response task, while both EC types performed similarly in age prediction. Our findings may suggest that different EC types could capture distinct phenotypic traits, with performance influenced by data processing and modeling choices. This evaluation may further promote the application of model-based approaches to behavior prediction from brain connectivity and enhance our understanding of the impact of data processing on the prediction results.

The neurodegenerative progression of Parkinson’s disease affects brain structure and function and, concomitantly, alters the topological properties of brain networks. The network alteration accompanied by motor impairment and the duration of the disease has not yet been clearly demonstrated in the disease progression. In this study, we aim to resolve this problem with a modeling approach using the reduced Jansen-Rit model applied to large-scale brain networks derived from cross-sectional MRI data. Optimizing whole-brain simulation models allows us to discover brain networks showing unexplored relationships with clinical variables. We observe that the simulated brain networks exhibit significant differences between healthy controls ( n = 51) and patients with Parkinson’s disease ( n = 60) and strongly correlate with disease severity and disease duration of the patients. Moreover, the modeling results outperform the empirical brain networks in these clinical measures. Consequently, this study demonstrates that utilizing the simulated brain networks provides an enhanced view of network alterations in the progression of motor impairment and identifies potential biomarkers for clinical indices. Author Summary Understanding the progression of neurodegenerative diseases is of extreme importance in medicine. We utilize biophysical whole-brain models to describe how the brain networks change in Parkinson’s disease (PD). We demonstrate clear correlations between the severity of motor impairment and the properties of the simulated brain networks, which are not prominent in empirical brain networks. Furthermore, we show that healthy participants exhibit a pronounced adaptation of network efficiencies in response to varying parameters of the model, while such an adaptation process is suppressed in PD patients with higher disease severity and duration. Our findings suggest a potential model-based biomarker for classification and clinical evaluation of progressive PD using cross-sectional clinical MRI data.

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.

Recent developments of whole-brain models have demonstrated their potential when investigating resting-state brain activity. However, it has not been systematically investigated how alternating derivations of the empirical structural and functional connectivity, serving as the model input, from MRI data influence modeling results. Here, we study the influence from one major element: the brain parcellation scheme that reduces the dimensionality of brain networks by grouping thousands of voxels into a few hundred brain regions. We show graph-theoretical statistics derived from the empirical data and modeling results exhibiting a high heterogeneity across parcellations. Furthermore, the network properties of empirical brain connectomes explain the lion’s share of the variance in the modeling results with respect to the parcellation variation. Such a clear-cut relationship is not observed at the subject-resolved level per parcellation. Finally, the graph-theoretical statistics of the simulated connectome correlate with those of the empirical functional connectivity across parcellations. However, this relation is not one-to-one, and its precision can vary between models. Our results imply that network properties of both empirical connectomes can explain the goodness-of-fit of whole-brain models to empirical data at a global group level but not at a single-subject level, which provides further insights into the personalization of whole-brain models. Author Summary The structural and functional connectivities of the brain, which reflect the anatomical connections of axonal bundles and the amount of coactivation between brain regions, respectively, only weakly correlate with each other. In order to enhance and investigate this relationship, large-scale whole-brain dynamical models were involved in this branch of research. However, how the definitions of the brain regions parcellated according to a so-called brain atlas influence these models has so far not been systematically assessed. In this article, we show that this influence can be large, and link group-averaged, atlas-induced deviations to network properties extracted from both types of connectivity. Additionally, we demonstrate that the same association does not apply to subject-specific variations. These results may contribute to the further personalization of the whole-brain models.

Cognitive processes do not occur by pure insertion and instead depend on the full complement of co-occurring mental processes, including perceptual and motor functions. As such, there is limited ecological validity to human neuroimaging experiments that use highly controlled tasks to isolate mental processes of interest. However, a growing literature shows how dynamic, interactive tasks have allowed researchers to study cognition as it more naturally occurs. Collective analysis across such neuroimaging experiments may answer broader questions regarding how naturalistic cognition is biologically distributed throughout the brain. We applied an unbiased, data-driven, meta-analytic approach that uses k -means clustering to identify core brain networks engaged across the naturalistic functional neuroimaging literature. Functional decoding allowed us to, then, delineate how information is distributed between these networks throughout the execution of dynamical cognition in realistic settings. This analysis revealed six recurrent patterns of brain activation, representing sensory, domain-specific, and attentional neural networks that support the cognitive demands of naturalistic paradigms. Although gaps in the literature remain, these results suggest that naturalistic fMRI paradigms recruit a common set of networks that allow both separate processing of different streams of information and integration of relevant information to enable flexible cognition and complex behavior. Author Summary Naturalistic fMRI paradigms offer increased ecological validity over traditional paradigms, addressing the gap left by studying highly interactive cognitive processes as isolated neural phenomena. This study identifies the connectional architecture supporting dynamic cognition in naturalistic fMRI paradigms, the first meta-analysis of a wide range of more realistic neuroimaging experiments. Here we identify and characterize six core patterns of neural activity that support functional segregation and integration in large-scale brain networks. This study provides a unique investigation of the cooperating neural systems that enable complex behavior.