Different whole-brain computational models have been recently developed to investigate hypotheses related to brain mechanisms. Among these, the Dynamic Mean Field (DMF) model is particularly attractive, combining a biophysically realistic model that is scaled up via a mean-field approach and multimodal imaging data. However, an important barrier to the widespread usage of the DMF model is that current implementations are computationally expensive, supporting only simulations on brain parcellations that consider less than 100 brain regions. Here, we introduce an efficient and accessible implementation of the DMF model: the FastDMF. By leveraging analytical and numerical advances—including a novel estimation of the feedback inhibition control parameter and a Bayesian optimization algorithm—the FastDMF circumvents various computational bottlenecks of previous implementations, improving interpretability, performance, and memory use. Furthermore, these advances allow the FastDMF to increase the number of simulated regions by one order of magnitude, as confirmed by the good fit to fMRI data parcellated at 90 and 1,000 regions. These advances open the way to the widespread use of biophysically grounded whole-brain models for investigating the interplay between anatomy, function, and brain dynamics and to identify mechanistic explanations of recent results obtained from fine-grained neuroimaging recordings.

The human brain is a complex system with high metabolic demands and extensive connectivity that requires control to balance energy consumption and functional efficiency over time. How this control is manifested on a whole-brain scale is largely unexplored, particularly what the associated costs are. Using the network control theory, here, we introduce a novel concept, time-averaged control energy (TCE), to quantify the cost of controlling human brain dynamics at rest, as measured from functional and diffusion MRI. Importantly, TCE spatially correlates with oxygen metabolism measures from the positron emission tomography, providing insight into the bioenergetic footing of resting-state control. Examining the temporal dimension of control costs, we find that brain state transitions along a hierarchical axis from sensory to association areas are more efficient in terms of control costs and more frequent within hierarchical groups than between. This inverse correlation between temporal control costs and state visits suggests a mechanism for maintaining functional diversity while minimizing energy expenditure. By unpacking the temporal dimension of control costs, we contribute to the neuroscientific understanding of how the brain governs its functionality while managing energy expenses. Author Summary Understanding how the brain balances functional efficiency with energy conservation is a central question in neuroscience. The network control theory (NCT) views this question from a network perspective where the brain manages signal propagations along its structural connections to transition across desired activity states. Our study thus presents a novel framework based on the NCT to analyze the costs associated with transitioning across resting states, revealing that regions with high control costs on average are also metabolically demanding in terms of oxygen use. Our findings further show that transitions between sensory and association states are infrequent due to high control costs, while transitions within these states are more common. This suggests that the brain employs a mechanism to preserve functional diversity while minimizing energy costs.

Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we investigated the changes in the brain’s functional hierarchy associated with two different psychedelics (LSD and psilocybin). Using a novel turbulence framework, we were able to determine the vorticity, that is, the local level of synchronization, that allowed us to extend the standard global time-based measure of metastability to become a local-based measure of both space and time. This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network. Overall, our findings directly support a prior hypothesis that psychedelics modulate (i.e., “compress”) the functional hierarchy and provide a quantification of these changes for two different psychedelics. Implications for therapeutic applications of psychedelics are discussed. Author Summary Significant progress has been made in understanding the effects of psychedelics on brain function. One of the main hypotheses is that psychedelics work by changing the functional hierarchy of brain dynamics in a dose-dependent manner, modulating the encoding of the precision of priors, beliefs, or assumptions in the brain. We used a novel turbulence framework to investigate the changes in the brain’s functional hierarchy associated with two different psychedelics (LSD and psilocybin). This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network.

Network neuroscience employs graph theory to investigate the human brain as a complex network, and derive generalizable insights about the brain’s network properties. However, graph-theoretical results obtained from network construction pipelines that produce idiosyncratic networks may not generalize when alternative pipelines are employed. This issue is especially pressing because a wide variety of network construction pipelines have been employed in the human network neuroscience literature, making comparisons between studies problematic. Here, we investigate how to produce networks that are maximally representative of the broader set of brain networks obtained from the same neuroimaging data. We do so by minimizing an information-theoretic measure of divergence between network topologies, known as the portrait divergence. Based on functional and diffusion MRI data from the Human Connectome Project, we consider anatomical, functional, and multimodal parcellations at three different scales, and 48 distinct ways of defining network edges. We show that the highest representativeness can be obtained by using parcellations in the order of 200 regions and filtering functional networks based on efficiency-cost optimization—though suitable alternatives are also highlighted. Overall, we identify specific node definition and thresholding procedures that neuroscientists can follow in order to derive representative networks from their human neuroimaging data.