Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence 1-6 . The brain's capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity 7-12 , here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; total N = 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortex's sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.
Deterministic chaos permits a precise notion of a "perfect measurement" as one that, when obtained repeatedly, captures all of the information created by the system's evolution with minimal redundancy. Finding an optimal measurement is challenging and has generally required intimate knowledge of the dynamics in the few cases where it has been done. We establish an equivalence between a perfect measurement and a variant of the information bottleneck. As a consequence, we can employ machine learning to optimize measurement processes that efficiently extract information from trajectory data. We obtain approximately optimal measurements for multiple chaotic maps and lay the necessary groundwork for efficient information extraction from general time series.
Humans are exposed to sequences of events in the environment, and the interevent transition probabilities in these sequences can be modeled as a graph or network. Many real-world networks are organized hierarchically and while much is known about how humans learn basic transition graph topology, whether and to what degree humans can learn hierarchical structures in such graphs remains unknown. We probe the mental estimates of transition probabilities via the surprisal effect phenomenon: humans react more slowly to less expected transitions. Using mean-field predictions and numerical simulations, we show that surprisal effects are stronger for finer-level than coarser-level hierarchical transitions, and that surprisal effects at coarser levels are difficult to detect for limited learning times or in small samples. Using a serial response experiment with human participants (n=100), we replicate our predictions by detecting a surprisal effect at the finer level of the hierarchy but not at the coarser level of the hierarchy. We then evaluate the presence of a trade-off in learning, whereby humans who learned the finer level of the hierarchy better also tended to learn the coarser level worse, and vice versa. This study elucidates the processes by which humans learn sequential events in hierarchical contexts. More broadly, our work charts a road map for future investigation of the neural underpinnings and behavioral manifestations of graph learning.
Learning , Humans , Male , Female , Models, Theoretical , Probability , Adult
What are the neural dynamics that drive creative thinking? Recent studies have provided much insight into the neural mechanisms of creative thought. Specifically, the interaction between the executive control, default mode, and salience brain networks has been shown to be an important marker of individual differences in creative ability. However, how these different brain systems might be recruited dynamically during the two key components of the creative process-generation and evaluation of ideas-remains far from understood. In the current study we applied state-of-the-art network neuroscience methodologies to examine the neural dynamics related to the generation and evaluation of creative and non-creative ideas using a novel within-subjects design. Participants completed two functional magnetic resonance imaging sessions, taking place a week apart. In the first imaging session, participants generated either creative (alternative uses) or non-creative (common characteristics) responses to common objects. In the second imaging session, participants evaluated their own creative and non-creative responses to the same objects. Network neuroscience methods were applied to examine and directly compare reconfiguration, integration, and recruitment of brain networks during these four conditions. We found that generating creative ideas led to significantly higher network reconfiguration than generating non-creative ideas, whereas evaluating creative and non-creative ideas led to similar levels of network integration. Furthermore, we found that these differences were attributable to different dynamic patterns of neural activity across the executive control, default mode, and salience networks. This study is the first to show within-subject differences in neural dynamics related to generating and evaluating creative and non-creative ideas.
BACKGROUND: Symptoms of borderline personality disorder (BPD) often manifest during adolescence, but the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here, we aimed to investigate how multivariate patterns of functional connectivity are associated with borderline personality traits in large samples of young adults and adolescents. METHODS: We used functional magnetic resonance imaging data from young adults and adolescents from the HCP-YA (Human Connectome Project Young Adult) (n = 870, ages 22-37 years, 457 female) and the HCP-D (Human Connectome Project Development) (n = 223, ages 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five-Factor Inventory. A ridge regression model with cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity. RESULTS: Multivariate functional connectivity patterns significantly predicted out-of-sample BPD scores in unseen data in young adults (HCP-YA ppermuted = .001) and older adolescents (HCP-D ppermuted = .001). Regional predictive capacity was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD scores aligned with those associated with development in youth. CONCLUSIONS: Individual differences in functional connectivity in developmentally sensitive regions are associated with borderline personality traits.
One of the fundamental steps toward understanding a complex system is identifying variation at the scale of the system's components that is most relevant to behavior on a macroscopic scale. Mutual information provides a natural means of linking variation across scales of a system due to its independence of functional relationship between observables. However, characterizing the manner in which information is distributed across a set of observables is computationally challenging and generally infeasible beyond a handful of measurements. Here, we propose a practical and general methodology that uses machine learning to decompose the information contained in a set of measurements by jointly optimizing a lossy compression of each measurement. Guided by the distributed information bottleneck as a learning objective, the information decomposition identifies the variation in the measurements of the system state most relevant to specified macroscale behavior. We focus our analysis on two paradigmatic complex systems: a Boolean circuit and an amorphous material undergoing plastic deformation. In both examples, the large amount of entropy of the system state is decomposed, bit by bit, in terms of what is most related to macroscale behavior. The identification of meaningful variation in data, with the full generality brought by information theory, is made practical for studying the connection between micro- and macroscale structure in complex systems.
Family conflict is an established predictor of psychopathology in youth. Traditional approaches focus on between-family differences in conflict. Daily fluctuations in conflict within families might also impact psychopathology, but more research is needed to understand how and why. Using 21 days of daily diary data and 6-times a day experience-sampling data (N = 77 participants; mean age = 21.18, SD = 1.75; 63 women, 14 men), we captured day-to-day and within-day fluctuations in family conflict, anger, anxiety, and sadness. Using multilevel models, we find that days of higher-than-usual anger are also days of higher-than-usual family conflict. Examining associations between family conflict and emotions within days, we find that moments of higher-than-usual anger predict higher-than-usual family conflict later in the day. We observe substantial between-family differences in these patterns with implications for psychopathology; youth showing the substantial interplay between family conflict and emotions across time had a more perseverative family conflict and greater trait anxiety. Overall, findings indicate the importance of increases in youth anger for experiences of family conflict during young adulthood and demonstrate how intensive repeated measures coupled with network analytic approaches can capture long-theorized notions of reciprocal processes in daily family life.
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology. Animal models carrying LRRK2 mutations do not develop robust PD-related phenotypes spontaneously, hampering the assessment of the efficacy of LRRK2 inhibitors against disease processes. We hypothesized that mutations in LRRK2 may not be directly related to a single disease pathway, but instead may elevate the susceptibility to multiple disease processes, depending on the disease trigger. To test this hypothesis, we have previously evaluated progression of α-synuclein and tau pathologies following injection of proteopathic seeds. We demonstrated that transgenic mice overexpressing mutant LRRK2 show alterations in the brain-wide progression of pathology, especially at older ages. METHODS: Here, we assess tau pathology progression in relation to long-term LRRK2 kinase inhibition. Wild-type or LRRK2G2019S knock-in mice were injected with tau fibrils and treated with control diet or diet containing LRRK2 kinase inhibitor MLi-2 targeting the IC50 or IC90 of LRRK2 for 3-6 months. Mice were evaluated for tau pathology by brain-wide quantitative pathology in 844 brain regions and subsequent linear diffusion modeling of progression. RESULTS: Consistent with our previous work, we found systemic alterations in the progression of tau pathology in LRRK2G2019S mice, which were most pronounced at 6 months. Importantly, LRRK2 kinase inhibition reversed these effects in LRRK2G2019S mice, but had minimal effect in wild-type mice, suggesting that LRRK2 kinase inhibition is likely to reverse specific disease processes in G2019S mutation carriers. Additional work may be necessary to determine the potential effect in non-carriers. CONCLUSIONS: This work supports a protective role of LRRK2 kinase inhibition in G2019S carriers and provides a rational workflow for systematic evaluation of brain-wide phenotypes in therapeutic development.
Brain , Dopaminergic Neurons , Animals , Humans , Mice , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Lewy Bodies , Mice, Transgenic , Mutation/genetics
In interacting dynamical systems, specific local interaction rules for system components give rise to diverse and complex global dynamics. Long dynamical cycles are a key feature of many natural interacting systems, especially in biology. Examples of dynamical cycles range from circadian rhythms regulating sleep to cell cycles regulating reproductive behavior. Despite the crucial role of cycles in nature, the properties of network structure that give rise to cycles still need to be better understood. Here, we use a Boolean interaction network model to study the relationships between network structure and cyclic dynamics. We identify particular structural motifs that support cycles, and other motifs that suppress them. More generally, we show that the presence of dynamical reflection symmetry in the interaction network enhances cyclic behavior. In simulating an artificial evolutionary process, we find that motifs that break reflection symmetry are discarded. We further show that dynamical reflection symmetries are over-represented in Boolean models of natural biological systems. Altogether, our results demonstrate a link between symmetry and functionality for interacting dynamical systems, and they provide evidence for symmetry's causal role in evolving dynamical functionality.
Head motion correction is particularly challenging in diffusion-weighted MRI (dMRI) scans due to the dramatic changes in image contrast at different gradient strengths and directions. Head motion correction is typically performed using a Gaussian Process model implemented in FSL's Eddy. Recently, the 3dSHORE-based SHORELine method was introduced that does not require shell-based acquisitions, but it has not been previously benchmarked. Here we perform a comprehensive evaluation of both methods on realistic simulations of a software fiber phantom that provides known ground-truth head motion. We demonstrate that both methods perform remarkably well, but that performance can be impacted by sampling scheme and the extent of head motion and the denoising strategy applied before head motion correction. Furthermore, we find Eddy benefits from denoising the data first with MP-PCA. In sum, we provide the most extensive known benchmarking of dMRI head motion correction, together with extensive simulation data and a reproducible workflow. PRACTITIONER POINTS: Both Eddy and SHORELine head motion correction methods performed quite well on a large variety of simulated data. Denoising with MP-PCA can improve head motion correction performance when Eddy is used. SHORELine effectively corrects motion in non-shelled diffusion spectrum imaging data.
Artifacts , Magnetic Resonance Imaging , Humans , Diffusion Magnetic Resonance Imaging/methods , Motion , Computer Simulation , Brain/diagnostic imaging , Algorithms , Image Processing, Computer-Assisted/methods
A fundamental goal of research in neuroscience is to uncover the causal structure of the brain. This focus on causation makes sense, because causal information can provide explanations of brain function and identify reliable targets with which to understand cognitive function and prevent or change neurological conditions and psychiatric disorders. In this research, one of the most frequently used causal concepts is 'mechanism' - this is seen in the literature and language of the field, in grant and funding inquiries that specify what research is supported, and in journal guidelines on which contributions are considered for publication. In these contexts, mechanisms are commonly tied to expressions of the main aims of the field and cited as the 'fundamental', 'foundational' and/or 'basic' unit for understanding the brain. Despite its common usage and perceived importance, mechanism is used in different ways that are rarely distinguished. Given that this concept is defined in different ways throughout the field - and that there is often no clarification of which definition is intended - there remains a marked ambiguity about the fundamental goals, orientation and principles of the field. Here we provide an overview of causation and mechanism from the perspectives of neuroscience and philosophy of science, in order to address these challenges.
Mental Disorders , Neurosciences , Humans , Cognition , Brain , Philosophy
Neurodevelopment is not merely a process of brain maturation, but an adaptation to constraints unique to each individual and to the environments we co-create. However, our theoretical and methodological toolkits often ignore this reality. There is growing awareness that a shift is needed that allows us to study divergence of brain and behaviour across conventional categorical boundaries. However, we argue that in future our study of divergence must also incorporate the developmental dynamics that capture the emergence of those neurodevelopmental differences. This crucial step will require adjustments in study design and methodology. If our ultimate aim is to incorporate the developmental dynamics that capture how, and ultimately when, divergence takes place then we will need an analytic toolkit equal to these ambitions. We argue that the over reliance on group averages has been a conceptual dead-end with regard to the neurodevelopmental differences. This is in part because any individual differences and developmental dynamics are inevitably lost within the group average. Instead, analytic approaches which are themselves new, or simply newly applied within this context, may allow us to shift our theoretical and methodological frameworks from groups to individuals. Likewise, methods capable of modelling complex dynamic systems may allow us to understand the emergent dynamics only possible at the level of an interacting neural system.
Brain , Research Design , Humans
[This corrects the article DOI: 10.1371/journal.pone.0294805.].
In the brain, functional connections form a network whose topological organization can be described by graph-theoretic network diagnostics. These include characterizations of the community structure, such as modularity and participation coefficient, which have been shown to change over the course of childhood and adolescence. To investigate if such changes in the functional network are associated with changes in cognitive performance during development, network studies often rely on an arbitrary choice of pre-processing parameters, in particular the proportional threshold of network edges. Because the choice of parameter can impact the value of the network diagnostic, and therefore downstream conclusions, we propose to circumvent that choice by conceptualizing the network diagnostic as a function of the parameter. As opposed to a single value, a network diagnostic curve describes the connectome topology at multiple scales-from the sparsest group of the strongest edges to the entire edge set. To relate these curves to executive function and other covariates, we use scalar-on-function regression, which is more flexible than previous functional data-based models used in network neuroscience. We then consider how systematic differences between networks can manifest in misalignment of diagnostic curves, and consequently propose a supervised curve alignment method that incorporates auxiliary information from other variables. Our algorithm performs both functional regression and alignment via an iterative, penalized, and nonlinear likelihood optimization. The illustrated method has the potential to improve the interpretability and generalizability of neuroscience studies where the goal is to study heterogeneity among a mixture of function- and scalar-valued measures.
It is typically assumed that large networks of neurons exhibit a large repertoire of nonlinear behaviours. Here we challenge this assumption by leveraging mathematical models derived from measurements of local field potentials via intracranial electroencephalography and of whole-brain blood-oxygen-level-dependent brain activity via functional magnetic resonance imaging. We used state-of-the-art linear and nonlinear families of models to describe spontaneous resting-state activity of 700 participants in the Human Connectome Project and 122 participants in the Restoring Active Memory project. We found that linear autoregressive models provide the best fit across both data types and three performance metrics: predictive power, computational complexity and the extent of the residual dynamics unexplained by the model. To explain this observation, we show that microscopic nonlinear dynamics can be counteracted or masked by four factors associated with macroscopic dynamics: averaging over space and over time, which are inherent to aggregated macroscopic brain activity, and observation noise and limited data samples, which stem from technological limitations. We therefore argue that easier-to-interpret linear models can faithfully describe macroscopic brain dynamics during resting-state conditions.
Brain , Connectome , Humans , Linear Models , Brain/physiology , Connectome/methods , Magnetic Resonance Imaging/methods , Models, Theoretical
The fairness of decisions made at various stages of the publication process is an important topic in meta-research. Here, based on an analysis of data on the gender of authors, editors and reviewers for 23,876 initial submissions and 7,192 full submissions to the journal eLife, we report on five stages of the publication process. We find that the board of reviewing editors (BRE) is men-dominant (69%) and that authors disproportionately suggest male editors when making an initial submission. We do not find evidence for gender bias when Senior Editors consult Reviewing Editors about initial submissions, but women Reviewing Editors are less engaged in discussions about these submissions than expected by their proportion. We find evidence of gender homophily when Senior Editors assign full submissions to Reviewing Editors (i.e., men are more likely to assign full submissions to other men (77% compared to the base assignment rate to men RE of 70%), and likewise for women (41% compared to women RE base assignment rate of 30%))). This tendency was stronger in more gender-balanced scientific disciplines. However, we do not find evidence for gender bias when authors appeal decisions made by editors to reject submissions. Together, our findings confirm that gender disparities exist along the editorial process and suggest that merely increasing the proportion of women might not be sufficient to eliminate this bias. Measures accounting for women's circumstances and needs (e.g., delaying discussions until all RE are engaged) and raising editorial awareness to women's needs may be essential to increasing gender equity and enhancing academic publication.
Research Report , Sexism , Humans , Male , Female
Evidence on the harms and benefits of social media use is mixed, in part because the effects of social media on well-being depend on a variety of individual difference moderators. Here, we explored potential neural moderators of the link between time spent on social media and subsequent negative affect. We specifically focused on the strength of correlation among brain regions within the frontoparietal system, previously associated with the top-down cognitive control of attention and emotion. Participants (N = 54) underwent a resting state functional magnetic resonance imaging scan. Participants then completed 28 days of ecological momentary assessment and answered questions about social media use and negative affect, twice a day. Participants who spent more than their typical amount of time on social media since the previous time point reported feeling more negative at the present moment. This within-person temporal association between social media use and negative affect was mainly driven by individuals with lower resting state functional connectivity within the frontoparietal system. By contrast, time spent on social media did not predict subsequent affect for individuals with higher frontoparietal functional connectivity. Our results highlight the moderating role of individual functional neural connectivity in the relationship between social media and affect.
Social Media , Humans , Brain Mapping , Brain/diagnostic imaging , Emotions , Magnetic Resonance Imaging/methods , Affect , Neural Pathways
Sex and gender are associated with human behavior throughout the lifespan and across health and disease, but whether they are associated with similar or distinct neural phenotypes is unknown. Here, we demonstrate that, in children, sex and gender are uniquely reflected in the intrinsic functional connectivity of the brain. Unimodal networks are more strongly associated with sex while heteromodal networks are more strongly associated with gender. These results suggest sex and gender are irreducible to one another not only in society but also in biology.
