One of the most well-established tools for modeling the brain is the functional connectivity network, which is constructed from pairs of interacting brain regions. While powerful, the network model is limited by the restriction that only pairwise dependencies are considered and potentially higher-order structures are missed. Here, we explore how multivariate information theory reveals higher-order dependencies in the human brain. We begin with a mathematical analysis of the O-information, showing analytically and numerically how it is related to previously established information theoretic measures of complexity. We then apply the O-information to brain data, showing that synergistic subsystems are widespread in the human brain. Highly synergistic subsystems typically sit between canonical functional networks, and may serve an integrative role. We then use simulated annealing to find maximally synergistic subsystems, finding that such systems typically comprise ≈10 brain regions, recruited from multiple canonical brain systems. Though ubiquitous, highly synergistic subsystems are invisible when considering pairwise functional connectivity, suggesting that higher-order dependencies form a kind of shadow structure that has been unrecognized by established network-based analyses. We assert that higher-order interactions in the brain represent an under-explored space that, accessible with tools of multivariate information theory, may offer novel scientific insights.

The standard approach to modeling the human brain as a complex system is with a network, where the basic unit of interaction is a pairwise link between two brain regions. While powerful, this approach is limited by the inability to assess higher-order interactions involving three or more elements directly. In this work, we explore a method for capturing higher-order dependencies in multivariate data: the partial entropy decomposition (PED). Our approach decomposes the joint entropy of the whole system into a set of nonnegative atoms that describe the redundant, unique, and synergistic interactions that compose the system’s structure. PED gives insight into the mathematics of functional connectivity and its limitation. When applied to resting-state fMRI data, we find robust evidence of higher-order synergies that are largely invisible to standard functional connectivity analyses. Our approach can also be localized in time, allowing a frame-by-frame analysis of how the distributions of redundancies and synergies change over the course of a recording. We find that different ensembles of regions can transiently change from being redundancy-dominated to synergy-dominated and that the temporal pattern is structured in time. These results provide strong evidence that there exists a large space of unexplored structures in human brain data that have been largely missed by a focus on bivariate network connectivity models. This synergistic structure is dynamic in time and likely will illuminate interesting links between brain and behavior. Beyond brain-specific application, the PED provides a very general approach for understanding higher-order structures in a variety of complex systems.

One of the essential functions of biological neural networks is the processing of information. This includes everything from processing sensory information to perceive the environment, up to processing motor information to interact with the environment. Due to methodological limitations, it has been historically unclear how information processing changes during different cognitive or behavioral states and to what extent information is processed within or between the network of neurons in different brain areas. In this study, we leverage recent advances in the calculation of information dynamics to explore neural-level processing within and between the frontoparietal areas AIP, F5, and M1 during a delayed grasping task performed by three macaque monkeys. While information processing was high within all areas during all cognitive and behavioral states of the task, interareal processing varied widely: During visuomotor transformation, AIP and F5 formed a reciprocally connected processing unit, while no processing was present between areas during the memory period. Movement execution was processed globally across all areas with predominance of processing in the feedback direction. Furthermore, the fine-scale network structure reconfigured at the neuron level in response to different grasping conditions, despite no differences in the overall amount of information present. These results suggest that areas dynamically form higher-order processing units according to the cognitive or behavioral demand and that the information-processing network is hierarchically organized at the neuron level, with the coarse network structure determining the behavioral state and finer changes reflecting different conditions.

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

Is reduction always a good scientific strategy? The existence of the special sciences above physics suggests not. Previous research has shown that dimensionality reduction (macroscales) can increase the dependency between elements of a system (a phenomenon called ‘causal emergence’). Here, we provide an umbrella mathematical framework for emergence based on information conversion. We show evidence that coarse-graining can convert information from one ‘type’ to another. We demonstrate this using the well-understood mutual information measure applied to Boolean networks. Using partial information decomposition, the mutual information can be decomposed into redundant, unique and synergistic information atoms. Then by introducing a novel measure of the synergy bias of a given decomposition, we are able to show that the synergy component of a Boolean network’s mutual information can increase at macroscales. This can occur even when there is no difference in the total mutual information between a macroscale and its underlying microscale, proving information conversion. We relate this broad framework to previous work, compare it to other theories, and argue it complexifies any notion of universal reduction in the sciences, since such reduction would likely lead to a loss of synergistic information in scientific models. This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.