Provincial and connector qualities of somatosensory brain network hubs in bipolar disorder.

Brain network hubs are highly connected brain regions serving as important relay stations for information integration. Recent studies have linked mental disorders to impaired hub function. Provincial hubs mainly integrate information within their own brain network, while connector hubs share information between different brain networks. This study used a novel time-varying analysis to investigate whether hubs aberrantly follow the trajectory of other brain networks than their own. The aim was to characterize brain hub functioning in clinically remitted bipolar patients. We analyzed resting-state functional magnetic resonance imaging data from 96 euthymic individuals with bipolar disorder and 61 healthy control individuals. We characterized different hub qualities within the somatomotor network. We found that the somatomotor network comprised mainly provincial hubs in healthy controls. Conversely, in bipolar disorder patients, hubs in the primary somatosensory cortex displayed weaker provincial and stronger connector hub function. Furthermore, hubs in bipolar disorder showed weaker allegiances with their own brain network and followed the trajectories of the limbic, salience, dorsal attention, and frontoparietal network. We suggest that these hub aberrancies contribute to previously shown functional connectivity alterations in bipolar disorder and may thus constitute the neural substrate to persistently impaired sensory integration despite clinical remission.

Taking the unreal seriously: enriching cognitive science with the notion of fictionality.

Fictionality and fictional experiences are ubiquitous in people's everyday lives in the forms of movies, novels, video games, pretense and role playing, and digital technology use. Despite this ubiquity, though, the field of cognitive science has traditionally been dominated by a focus on the real world. Based on the limited understanding from previous research on questions regarding fictional information and the cognitive processes for distinguishing reality from fiction, we argue for the need for a comprehensive and systematic account that reflects on related phenomena, such as narrative comprehension or imagination embedded into general theories of cognition. This is important as incorporating cognitive processing of fictional events into memory theory reshapes the conceptual map of human memory. In this paper, we highlight future challenges for the cognitive studies of fictionality on conceptual, neurological, and computational levels. Taking on these challenges requires an interdisciplinary approach between fields like developmental psychology, philosophy, and the study of narrative comprehension. Our aim is to build on such interdisciplinarity and provide conclusions on the ways in which new theoretical frameworks of fiction cognition can aid understanding human behaviors in a wide range of aspects of people's daily lives, media consumption habits, and digital encounters. Our account also has the potential to inform technological innovations related to training intelligent digital systems to distinguish fact and fiction in the source material.

On the scope of scientific hypotheses.

Hypotheses are frequently the starting point when undertaking the empirical portion of the scientific process. They state something that the scientific process will attempt to evaluate, corroborate, verify or falsify. Their purpose is to guide the types of data we collect, analyses we conduct, and inferences we would like to make. Over the last decade, metascience has advocated for hypotheses being in preregistrations or registered reports, but how to formulate these hypotheses has received less attention. Here, we argue that hypotheses can vary in specificity along at least three independent dimensions: the relationship, the variables, and the pipeline. Together, these dimensions form the scope of the hypothesis. We demonstrate how narrowing the scope of a hypothesis in any of these three ways reduces the hypothesis space and that this reduction is a type of novelty. Finally, we discuss how this formulation of hypotheses can guide researchers to formulate the appropriate scope for their hypotheses and should aim for neither too broad nor too narrow a scope. This framework can guide hypothesis-makers when formulating their hypotheses by helping clarify what is being tested, chaining results to previous known findings, and demarcating what is explicitly tested in the hypothesis.

NetPlotBrain: A Python package for visualizing networks and brains.

Visualizations of networks are complex since they are multidimensional and generally convey large amounts of information. The layout of the visualization can communicate either network properties or spatial properties of the network. Generating such figures to effectively convey information and be accurate can be difficult and time-consuming, and it can require expert knowledge. Here, we introduce NetPlotBrain (short for network plots onto brains), a Python package for Python 3.9+. The package offers several advantages. First, NetPlotBrain provides a high-level interface to easily highlight and customize results of interest. Second, it presents a solution to promote accurate plots through its integration with TemplateFlow. Third, it integrates with other Python software, allowing for easy integration to include networks from NetworkX or implementations of network-based statistics. In sum, NetPlotBrain is a versatile but easy to use package designed to produce high-quality network figures while integrating with open research software for neuroimaging and network theory.

Segregation over time in functional networks in prefrontal cortex for individuals suffering from pathological fatigue after traumatic brain injury.

Pathological fatigue is present when fatigue is perceived to continually interfere with everyday life. Pathological fatigue has been linked with a dysfunction in the cortico-striatal-thalamic circuits. Previous studies have investigated measures of functional connectivity, such as modularity to quantify levels of segregation. However, previous results have shown both increases and decreases in segregation for pathological fatigue. There are multiple factors why previous studies might have differing results, including: (i) Does the functional connectivity of patients with pathological fatigue display more segregation or integration compared to healthy controls? (ii) Do network properties differ depending on whether patients with pathological fatigue perform a task compared to periods of rest? (iii) Are the brain networks of patients with pathological fatigue and healthy controls differently affected by prolonged cognitive activity? We recruited individuals suffering from pathological fatigue after mild traumatic brain injury (n = 20) and age-matched healthy controls (n = 20) to perform cognitive tasks for 2.5 h. We used functional near-infrared spectroscopy (fNIRS) to assess hemodynamic changes in the frontal cortex. The participants had a resting state session before and after the cognitive test session. Cognitive testing included the Digit Symbol Coding test at the beginning and the end of the procedure to measure processing speed. We conducted an exploratory network analysis on these resting state and Digit Symbol Coding sessions with no a priori hypothesis relating to how patients and controls differ in their functional networks since previous research has found results in both directions. Our result showed a Group vs. Time interaction (p = 0.026, η p 2 = 0.137), with a post hoc test revealing that the TBI patients developed higher modularity toward the end of the cognitive test session. This work helps to identify how functional networks differ under pathological fatigue compared to healthy controls. Further, it shows how the functional networks dynamically change over time as the patient performs tasks over a time scale that affect their fatigue level.

Dataset decay and the problem of sequential analyses on open datasets.

Open data allows researchers to explore pre-existing datasets in new ways. However, if many researchers reuse the same dataset, multiple statistical testing may increase false positives. Here we demonstrate that sequential hypothesis testing on the same dataset by multiple researchers can inflate error rates. We go on to discuss a number of correction procedures that can reduce the number of false positives, and the challenges associated with these correction procedures.

Questions and controversies in the study of time-varying functional connectivity in resting fMRI.

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain's functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as "dynamic" or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience.

Time-varying nodal measures with temporal community structure: A cautionary note to avoid misinterpretation.

In network neuroscience, temporal network models have gained popularity. In these models, network properties have been related to cognition and behavior. Here, we demonstrate that calculating nodal properties that are dependent on temporal community structure (such as the participation coefficient [PC]) in time-varying contexts can potentially lead to misleading results. Specifically, with regards to the participation coefficient, increases in integration can be inferred when the opposite is occurring. Further, we present a temporal extension to the PC measure (temporal PC) that circumnavigates this problem by jointly considering all community partitions assigned to a node through time. The proposed method allows us to track a node's integration through time while adjusting for the possible changes in the community structure of the overall network.

Open exploration.

Arguments in support of open science tend to focus on confirmatory research practices. Here we argue that exploratory research should also be encouraged within the framework of open science. We lay out the benefits of 'open exploration' and propose two complementary ways to implement this with little infrastructural change.

Brain network segregation and integration during an epoch-related working memory fMRI experiment.

The characterization of brain subnetwork segregation and integration has previously focused on changes that are detectable at the level of entire sessions or epochs of imaging data. In this study, we applied time-varying functional connectivity analysis together with temporal network theory to calculate point-by-point estimates in subnetwork segregation and integration during an epoch-based (2-back, 0-back, baseline) working memory fMRI experiment as well as during resting-state. This approach allowed us to follow task-related changes in subnetwork segregation and integration at a high temporal resolution. At a global level, the cognitively more taxing 2-back epochs elicited an overall stronger response of integration between subnetworks compared to the 0-back epochs. Moreover, the visual, sensorimotor and fronto-parietal subnetworks displayed characteristic and distinct temporal profiles of segregation and integration during the 0- and 2-back epochs. During the interspersed epochs of baseline, several subnetworks, including the visual, fronto-parietal, cingulo-opercular and dorsal attention subnetworks showed pronounced increases in segregation. Using a drift diffusion model we show that the response time for the 2-back trials are correlated with integration for the fronto-parietal subnetwork and correlated with segregation for the visual subnetwork. Our results elucidate the fast-evolving events with regard to subnetwork integration and segregation that occur in an epoch-related task fMRI experiment. Our findings suggest that minute changes in subnetwork integration are of importance for task performance.

Simulations to benchmark time-varying connectivity methods for fMRI.

There is a current interest in quantifying time-varying connectivity (TVC) based on neuroimaging data such as fMRI. Many methods have been proposed, and are being applied, revealing new insight into the brain's dynamics. However, given that the ground truth for TVC in the brain is unknown, many concerns remain regarding the accuracy of proposed estimates. Since there exist many TVC methods it is difficult to assess differences in time-varying connectivity between studies. In this paper, we present tvc_benchmarker, which is a Python package containing four simulations to test TVC methods. Here, we evaluate five different methods that together represent a wide spectrum of current approaches to estimating TVC (sliding window, tapered sliding window, multiplication of temporal derivatives, spatial distance and jackknife correlation). These simulations were designed to test each method's ability to track changes in covariance over time, which is a key property in TVC analysis. We found that all tested methods correlated positively with each other, but there were large differences in the strength of the correlations between methods. To facilitate comparisons with future TVC methods, we propose that the described simulations can act as benchmark tests for evaluation of methods. Using tvc_benchmarker researchers can easily add, compare and submit their own TVC methods to evaluate its performance.

A common framework for the problem of deriving estimates of dynamic functional brain connectivity.

The research field of dynamic functional connectivity explores the temporal properties of brain connectivity. To date, many methods have been proposed, which are based on quite different assumptions. In order to understand in which way the results from different techniques can be compared to each other, it is useful to be able to formulate them within a common theoretical framework. In this study, we describe such a framework that is suitable for many of the dynamic functional connectivity methods that have been proposed. Our overall intention was to derive a theoretical framework that was constructed such that a wide variety of dynamic functional connectivity techniques could be expressed and evaluated within the same framework. At the same time, care was given to the fact that key features of each technique could be easily illustrated within the framework and thus highlighting critical assumptions that are made. We aimed to create a common framework which should serve to assist comparisons between different analytical methods for dynamic functional brain connectivity and promote an understanding of their methodological advantages as well as potential drawbacks.

The readability of scientific texts is decreasing over time.

Clarity and accuracy of reporting are fundamental to the scientific process. Readability formulas can estimate how difficult a text is to read. Here, in a corpus consisting of 709,577 abstracts published between 1881 and 2015 from 123 scientific journals, we show that the readability of science is steadily decreasing. Our analyses show that this trend is indicative of a growing use of general scientific jargon. These results are concerning for scientists and for the wider public, as they impact both the reproducibility and accessibility of research findings.

Spatial confluence of psychological and anatomical network constructs in the human brain revealed by a mass meta-analysis of fMRI activation.

It is well-known that the brain's activity is organized into networks but it is unclear how many networks exist. Additionally, there is also a risk of ambiguity since different names for the same network are frequently reported in the literature. In this study, we employed a mass meta-analysis of fMRI data associated with network constructs originating from both psychology and neuroscience. Based on the results from the meta-analysis, we derived a spatial similarity map between all construct terms, showing that the brain's networks cluster hierarchically into several levels. The results presented are useful as a first step in developing a unified terminology for large-scale brain network and a platform for a queryable network atlas.

From static to temporal network theory: Applications to functional brain connectivity.

Network neuroscience has become an established paradigm to tackle questions related to the functional and structural connectome of the brain. Recently, interest has been growing in examining the temporal dynamics of the brain's network activity. Although different approaches to capturing fluctuations in brain connectivity have been proposed, there have been few attempts to quantify these fluctuations using temporal network theory. This theory is an extension of network theory that has been successfully applied to the modeling of dynamic processes in economics, social sciences, and engineering article but it has not been adopted to a great extent within network neuroscience. The objective of this article is twofold: (i) to present a detailed description of the central tenets of temporal network theory and describe its measures, and; (ii) to apply these measures to a resting-state fMRI dataset to illustrate their utility. Furthermore, we discuss the interpretation of temporal network theory in the context of the dynamic functional brain connectome. All the temporal network measures and plotting functions described in this article are freely available as the Python package Teneto.

Bursty properties revealed in large-scale brain networks with a point-based method for dynamic functional connectivity.

The brain is organized into large scale spatial networks that can be detected during periods of rest using fMRI. The brain is also a dynamic organ with activity that changes over time. We developed a method and investigated properties where the connections as a function of time are derived and quantified. The point based method (PBM) presented here derives covariance matrices after clustering individual time points based upon their global spatial pattern. This method achieved increased temporal sensitivity, together with temporal network theory, allowed us to study functional integration between resting-state networks. Our results show that functional integrations between two resting-state networks predominately occurs in bursts of activity. This is followed by varying intermittent periods of less connectivity. The described point-based method of dynamic resting-state functional connectivity allows for a detailed and expanded view on the temporal dynamics of resting-state connectivity that provides novel insights into how neuronal information processing is integrated in the human brain at the level of large-scale networks.

Functional resting-state fMRI connectivity correlates with serum levels of the S100B protein in the acute phase of traumatic brain injury.

The S100B protein is an intra-cellular calcium-binding protein that mainly resides in astrocytes in the central nervous system. The serum level of S100B is used as biomarker for the severity of brain damage in traumatic brain injury (TBI) patients. In this study we investigated the relationship between intrinsic resting-state brain connectivity, measured 1-22 days (mean 8 days) after trauma, and serum levels of S100B in a patient cohort with mild-to-severe TBI in need of neuro-intensive care in the acute phase. In line with previous investigations, our results show that the peak level of S100B acquired during the acute phase of TBI was negatively correlated with behavioral measures (Glasgow Outcome Score, GOS) of functional outcome assessed 6 to 12 months post injury. Using a multi-variate pattern analysis-informed seed-based correlation analysis, we show that the strength of resting-state brain connectivity in multiple resting-state networks was negatively correlated with the peak of serum levels of S100B. A negative correspondence between S100B peak levels recorded 12-36 h after trauma and intrinsic connectivity was found for brain regions located in the default mode, fronto-parietal, visual and motor resting-state networks. Our results suggest that resting-state brain connectivity measures acquired during the acute phase of TBI is concordant with results obtained from molecular biomarkers and that it may hold a capacity to predict long-term cognitive outcome in TBI patients.

On Stabilizing the Variance of Dynamic Functional Brain Connectivity Time Series.

Assessment of dynamic functional brain connectivity based on functional magnetic resonance imaging (fMRI) data is an increasingly popular strategy to investigate temporal dynamics of the brain's large-scale network architecture. Current practice when deriving connectivity estimates over time is to use the Fisher transformation, which aims to stabilize the variance of correlation values that fluctuate around varying true correlation values. It is, however, unclear how well the stabilization of signal variance performed by the Fisher transformation works for each connectivity time series, when the true correlation is assumed to be fluctuating. This is of importance because many subsequent analyses either assume or perform better when the time series have stable variance or adheres to an approximate Gaussian distribution. In this article, using simulations and analysis of resting-state fMRI data, we analyze the effect of applying different variance stabilization strategies on connectivity time series. We focus our investigation on the Fisher transformation, the Box-Cox (BC) transformation and an approach that combines both transformations. Our results show that, if the intention of stabilizing the variance is to use metrics on the time series, where stable variance or a Gaussian distribution is desired (e.g., clustering), the Fisher transformation is not optimal and may even skew connectivity time series away from being Gaussian. Furthermore, we show that the suboptimal performance of the Fisher transformation can be substantially improved by including an additional BC transformation after the dynamic functional connectivity time series has been Fisher transformed.

The frequency dimension of fMRI dynamic connectivity: Network connectivity, functional hubs and integration in the resting brain.

The large-scale functional MRI connectome of the human brain is composed of multiple resting-state networks (RSNs). However, the network dynamics, such as integration and segregation between and within RSNs is largely unknown. To address this question we created high-resolution "frequency graphlets", connectivity matrices derived across the low-frequency spectrum of the BOLD fMRI resting-state signal (0.01-0.1 Hz) in a cohort of 100 subjects. We then apply and compare graph theoretical measures across the frequency graphlets. Our results show that the within- and between-network connectivity and presence of functional hubs shift as a function of frequency. Furthermore, we show that the small world network property peaks at different frequencies with corresponding spatial connectivity profiles. We conclude that the frequency dependence of the network connectivity and the spatial configuration of functional hubs suggest that the dynamics of large-scale network integration and segregation operate at different time scales.