Neuroscience meets behavior: A systematic literature review on magnetic resonance imaging of the brain combined with real-world digital phenotyping.

A primary goal of neuroscience is to understand the relationship between the brain and behavior. While magnetic resonance imaging (MRI) examines brain structure and function under controlled conditions, digital phenotyping via portable automatic devices (PAD) quantifies behavior in real-world settings. Combining these two technologies may bridge the gap between brain imaging, physiology, and real-time behavior, enhancing the generalizability of laboratory and clinical findings. However, the use of MRI and data from PADs outside the MRI scanner remains underexplored. Herein, we present a Preferred Reporting Items for Systematic Reviews and Meta-Analysis systematic literature review that identifies and analyzes the current state of research on the integration of brain MRI and PADs. PubMed and Scopus were automatically searched using keywords covering various MRI techniques and PADs. Abstracts were screened to only include articles that collected MRI brain data and PAD data outside the laboratory environment. Full-text screening was then conducted to ensure included articles combined quantitative data from MRI with data from PADs, yielding 94 selected papers for a total of N = 14,778 subjects. Results were reported as cross-frequency tables between brain imaging and behavior sampling methods and patterns were identified through network analysis. Furthermore, brain maps reported in the studies were synthesized according to the measurement modalities that were used. Results demonstrate the feasibility of integrating MRI and PADs across various study designs, patient and control populations, and age groups. The majority of published literature combines functional, T1-weighted, and diffusion weighted MRI with physical activity sensors, ecological momentary assessment via PADs, and sleep. The literature further highlights specific brain regions frequently correlated with distinct MRI-PAD combinations. These combinations enable in-depth studies on how physiology, brain function and behavior influence each other. Our review highlights the potential for constructing brain-behavior models that extend beyond the scanner and into real-world contexts.

FreeSurfer 7 quality control: Key problem areas and importance of manual corrections.

We have studied the effects of manual quality control of brain Magnetic Resonance Imaging (MRI) images processed with Freesurfer. T1 images of first episode psychosis patients (N = 60) and healthy controls (N = 41) were inspected for gray matter boundary errors. The errors were fixed, and the effects of error correction on brain volume, thickness, and surface area were measured. It is commonplace to apply quality control to Freesurfer MRI recordings to ensure that the edges of gray and white matter are detected properly, as incorrect edge detection leads to changes in variables such as volume, cortical thickness, and cortical surface area. We find that while Freesurfer v7.1.1. does regularly make mistakes in identifying the edges of cortical gray matter, correcting these errors yields limited changes in the commonly measured variables listed above. We further find that the software makes fewer gray matter boundary errors when processing female brains. The results suggest that manually correcting gray matter boundary errors may not be worthwhile due to its small effect on the measurements, with potential exceptions for studies that focus on the areas that are more commonly affected by errors: the areas around the cerebellar tentorium, paracentral lobule, and the optic nerves, specifically the horizontal segment of the middle cerebral artery.

Universal patterns in egocentric communication networks.

Tie strengths in social networks are heterogeneous, with strong and weak ties playing different roles at the network and individual levels. Egocentric networks, networks of relationships around an individual, exhibit few strong ties and more weaker ties, as evidenced by electronic communication records. Mobile phone data has also revealed persistent individual differences within this pattern. However, the generality and driving mechanisms of social tie strength heterogeneity remain unclear. Here, we study tie strengths in egocentric networks across multiple datasets of interactions between millions of people during months to years. We find universality in tie strength distributions and their individual-level variation across communication modes, even in channels not reflecting offline social relationships. Via a simple model of egocentric network evolution, we show that the observed universality arises from the competition between cumulative advantage and random choice, two tie reinforcement mechanisms whose balance determines the diversity of tie strengths. Our results provide insight into the driving mechanisms of tie strength heterogeneity in social networks and have implications for the understanding of social network structure and individual behavior.

Critical Drift in a Neuro-Inspired Adaptive Network.

It has been postulated that the brain operates in a self-organized critical state that brings multiple benefits, such as optimal sensitivity to input. Thus far, self-organized criticality has typically been depicted as a one-dimensional process, where one parameter is tuned to a critical value. However, the number of adjustable parameters in the brain is vast, and hence critical states can be expected to occupy a high-dimensional manifold inside a high-dimensional parameter space. Here, we show that adaptation rules inspired by homeostatic plasticity drive a neuro-inspired network to drift on a critical manifold, where the system is poised between inactivity and persistent activity. During the drift, global network parameters continue to change while the system remains at criticality.

Analysis of thymic generation of shared T-cell receptor α repertoire associated with recognition of tumor antigens shows no preference for neoantigens over wild-type antigens.

BACKGROUND: The number of mutations in cancer cells is an important predictor of a positive response to cancer immunotherapy. It has been suggested that the neoantigens produced by these mutations are more immunogenic than nonmutated tumor antigens, which are likely to be protected by immunological tolerance. However, the mechanisms of tolerance as regards tumor antigens are incompletely understood. METHODS: Here, we have analyzed the impact of thymic negative selection on shared T-cell receptor (TCR) repertoire associated with the recognition of either mutated or nonmutated tumor antigens by comparing previously known TCR-antigen-pairs to TCR repertoires of 21 immunologically healthy individuals. RESULTS: Our results show that TCRα chains associated with either type of tumor antigens are readily generated in the thymus, at a frequency similar to TCRα chains associated with nonself. In the peripheral repertoire, the relative clone size of nonself-associated chains is higher than that of the tumor antigens, but importantly, there is no difference between TCRα chains associated with mutated or nonmutated tumor antigens. CONCLUSION: This suggests that the tolerance mechanisms protecting nonmutated tumor antigens are non-deletional and therefore potentially reversible. As unmutated antigens are, unlike mutations, shared by a large number of patients, they may offer advantages in designing immunological approaches to cancer treatment.

Herd immunity and epidemic size in networks with vaccination homophily.

We study how the herd immunity threshold and the expected epidemic size depend on homophily with respect to vaccine adoption. We find that the presence of homophily considerably increases the critical vaccine coverage needed for herd immunity and that strong homophily can push the threshold entirely out of reach. The epidemic size monotonically increases as a function of homophily strength for a perfect vaccine, while it is maximized at a nontrivial level of homophily when the vaccine efficacy is limited. Our results highlight the importance of vaccination homophily in epidemic modeling.

Quantifying daily rhythms with non-negative matrix factorization applied to mobile phone data.

Human activities follow daily, weekly, and seasonal rhythms. The emergence of these rhythms is related to physiology and natural cycles as well as social constructs. The human body and its biological functions undergo near 24-h rhythms (circadian rhythms). While their frequencies are similar across people, their phases differ. In the chronobiology literature, people are categorized into morning-type, evening-type, and intermediate-type groups called chronotypes based on their tendency to sleep at different times of day. Typically, this typology builds on carefully designed questionnaires or manually crafted features of time series data on people's activity. Here, we introduce a method where time-stamped data from smartphones are decomposed into components using non-negative matrix factorization. The method does not require any predetermined assumptions about the typical times of sleep or activity: the results are fully context-dependent and determined by the most prominent features of the activity data. We demonstrate our method by applying it to a dataset of mobile phone screen usage logs of 400 university students, collected over a year. We find four emergent temporal components: morning activity, night activity, evening activity and activity at noon. Individual behavior can be reduced to weights on these four components. We do not observe any clear categories of people based on the weights, but individuals are rather placed on a continuous spectrum according to the timings of their phone activities. High weights for the morning and night components strongly correlate with sleep and wake-up times. Our work points towards a data-driven way of characterizing people based on their full daily and weekly rhythms of activity and behavior, instead of only focusing on the timing of their sleeping periods.

Peripheral differentiation patterns of human T cells.

Long-term T-cell memory is dependent on the maintenance of memory T cells in the lymphoid tissues, and at the surface interfaces that provide entry routes for pathogens. However, much of the current information on human T-cell memory is based on analyzing circulating T cells. Here, we have studied the distribution and age-related changes of memory T-cell subsets in samples from blood, mesenteric LNs, spleen, and ileum, obtained from donors ranging in age from 5 days to 67 years of age. Our data show that the main reservoir of polyclonal naive cells is found in the LNs, and the resting memory subsets capable of self-renewal are also prominent there. In contrast, nondividing but functionally active memory subsets dominate the spleen, and especially the ileum. In general, the replacement of naive cells with memory subsets continues throughout our period of observation, with no apparent plateau. In conclusion, the analysis of lymphoid and nonlymphoid tissues reveals a dynamic pattern of changes distinct to each tissue, and with substantial differences between CD4+ and CD8+ compartments.

Mobility Signatures: A Tool for Characterizing Cities Using Intercity Mobility Flows.

Understanding the patterns of human mobility between cities has various applications from transport engineering to spatial modeling of the spreading of contagious diseases. We adopt a city-centric, data-driven perspective to quantify such patterns and introduce the mobility signature as a tool for understanding how a city (or a region) is embedded in the wider mobility network. We demonstrate the potential of the mobility signature approach through two applications that build on mobile-phone-based data from Finland. First, we use mobility signatures to show that the well-known radiation model is more accurate for mobility flows associated with larger Finnish cities, while the traditional gravity model appears a better fit for less populated areas. Second, we illustrate how the SARS-CoV-2 pandemic disrupted the mobility patterns in Finland in the spring of 2020. These two cases demonstrate the ability of the mobility signatures to quickly capture features of mobility flows that are harder to extract using more traditional methods.

Generation of self-reactive, shared T-cell receptor α chains in the human thymus.

The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing of TCRα to TCRß chains with the estimated total TCR diversity of >108. Despite this high diversity, similar or identical TCR chains are found to recur in immune responses. Here, we analyzed the thymic generation of TCR sequences previously associated with recognition of self- and nonself-antigens, represented by sequences associated with autoimmune diabetes and HIV, respectively. Unexpectedly, in the CD4+ compartment TCRα chains associated with the recognition of self-antigens were generated in significantly higher numbers than TCRα chains associated with the recognition of nonself-antigens. The analysis of the circulating repertoire further showed that these chains are not lost in negative selection nor predominantly converted to the regulatory T-cell lineage. The high abundance of self-reactive TCRα chains in multiple individuals suggests that the human thymus has a predilection to generate self-reactive TCRα chains independently of the HLA-type and that the individual risk of autoimmunity may be modulated by the TCRß repertoire associated with these chains.

Characterization of human T cell receptor repertoire data in eight thymus samples and four related blood samples.

T cell receptor (TCR) is a heterodimer consisting of TCRα and TCRß chains that are generated by somatic recombination of multiple gene segments. Nascent TCR repertoire undergoes thymic selections where non-functional and potentially autoreactive receptors are removed. During the last years, the development of high-throughput sequencing technology has allowed a large scale assessment of TCR repertoire and multiple analysis tools are now also available. In our recent manuscript, Human thymic T cell repertoire is imprinted with strong convergence to shared sequences[1], we show highly overlapping thymic TCR repertoires in unrelated individuals. In the current Data in Brief article, we provide a more detailed characterization of the basic features of these thymic and related peripheral blood TCR repertoires. The thymus samples were collected from eight infants undergoing corrective cardiac surgery, two of whom were monozygous twins [2]. In parallel with the surgery, a small aliquot of peripheral blood was drawn from four of the donors. Genomic DNA was extracted from mechanically released thymocytes and circulating leukocytes. The sequencing of TCRα and TCRß repertoires was performed at ImmunoSEQ platform (Adaptive Biotechnologies). The obtained repertoire data were analysed applying relevant features from immunoSEQ® 3.0 Analyzer (Adaptive Biotechnologies) and a freely available VDJTools software package for programming language R [3]. The current data analysis displays the basic features of the sequenced repertoires including observed TCR diversity, various descriptive TCR diversity measures, and V and J gene usage. In addition, multiple methods to calculate repertoire overlap between two individuals are applied. The raw sequence data provide a large database of reference TCRs in healthy individuals at an early developmental stage. The data can be exploited to improve existing computational models on TCR repertoire behaviour as well as in the generation of new models.

Human thymic T cell repertoire is imprinted with strong convergence to shared sequences.

A highly diverse repertoire of T cell antigen receptors (TCR) is created in the thymus by recombination of gene segments and the insertion or deletion of nucleotides at the junctions. Using next-generation TCR sequencing we define here the features of recombination and selection in the human TCRα and TCRß locus, and show that a strikingly high proportion of the repertoire is shared by unrelated individuals. The thymic TCRα nucleotide repertoire was more diverse than TCRß, with 4.1 × 106 vs. 0.81 × 106 unique clonotypes, and contained nonproductive clonotypes at a higher frequency (69.2% vs. 21.2%). The convergence of distinct nucleotide clonotypes to the same amino acid sequences was higher in TCRα than in TCRß repertoire (1.45 vs. 1.06 nucleotide sequences per amino acid sequence in thymus). The gene segment usage was biased, and generally all individuals favored the same genes in both TCRα and TCRß loci. Despite the high diversity, a large fraction of the repertoire was found in more than one donor. The shared fraction was bigger in TCRα than TCRß repertoire, and more common in in-frame sequences than in nonproductive sequences. Thus, both biases in rearrangement and thymic selection are likely to contribute to the generation of shared repertoire in humans.

Effects of spatial smoothing on group-level differences in functional brain networks.

Brain connectivity with functional magnetic resonance imaging (fMRI) is a popular approach for detecting differences between healthy and clinical populations. Before creating a functional brain network, the fMRI time series must undergo several preprocessing steps to control for artifacts and to improve data quality. However, preprocessing may affect the results in an undesirable way. Spatial smoothing, for example, is known to alter functional network structure. Yet, its effects on group-level network differences remain unknown. Here, we investigate the effects of spatial smoothing on the difference between patients and controls for two clinical conditions: autism spectrum disorder and bipolar disorder, considering fMRI data smoothed with Gaussian kernels (0-32 mm). We find that smoothing affects network differences between groups. For weighted networks, incrementing the smoothing kernel makes networks more different. For thresholded networks, larger smoothing kernels lead to more similar networks, although this depends on the network density. Smoothing also alters the effect sizes of the individual link differences. This is independent of the region of interest (ROI) size, but varies with link length. The effects of spatial smoothing are diverse, nontrivial, and difficult to predict. This has important consequences: The choice of smoothing kernel affects the observed network differences.

Identifying the inheritable component of human thymic T cell repertoire generation in monozygous twins.

We have analyzed T cell receptor repertoires in a unique set of thymus samples from a pair of monozygotic twins. While genetics affect the V(D)J rearrangement and generation of junctional sequences, the thymic selections seem largely stochastic and import no detectable inheritable effect at clonal level.

Regions of Interest as nodes of dynamic functional brain networks.

The properties of functional brain networks strongly depend on how their nodes are chosen. Commonly, nodes are defined by Regions of Interest (ROIs), predetermined groupings of fMRI measurement voxels. Earlier, we demonstrated that the functional homogeneity of ROIs, captured by their spatial consistency, varies widely across ROIs in commonly used brain atlases. Here, we ask how ROIs behave as nodes of dynamic brain networks. To this end, we use two measures: spatiotemporal consistency measures changes in spatial consistency across time and network turnover quantifies the changes in the local network structure around an ROI. We find that spatial consistency varies non-uniformly in space and time, which is reflected in the variation of spatiotemporal consistency across ROIs. Furthermore, we see time-dependent changes in the network neighborhoods of the ROIs, reflected in high network turnover. Network turnover is nonuniformly distributed across ROIs: ROIs with high spatiotemporal consistency have low network turnover. Finally, we reveal that there is rich voxel-level correlation structure inside ROIs. Because the internal structure and the connectivity of ROIs vary in time, the common approach of using static node definitions may be surprisingly inaccurate. Therefore, network neuroscience would greatly benefit from node definition strategies tailored for dynamical networks.

Mapping temporal-network percolation to weighted, static event graphs.

The dynamics of diffusion-like processes on temporal networks are influenced by correlations in the times of contacts. This influence is particularly strong for processes where the spreading agent has a limited lifetime at nodes: disease spreading (recovery time), diffusion of rumors (lifetime of information), and passenger routing (maximum acceptable time between transfers). We introduce weighted event graphs as a powerful and fast framework for studying connectivity determined by time-respecting paths where the allowed waiting times between contacts have an upper limit. We study percolation on the weighted event graphs and in the underlying temporal networks, with simulated and real-world networks. We show that this type of temporal-network percolation is analogous to directed percolation, and that it can be characterized by multiple order parameters.

A collection of public transport network data sets for 25 cities.

Various public transport (PT) agencies publish their route and timetable information with the General Transit Feed Specification (GTFS) as the standard open format. Timetable data are commonly used for PT passenger routing. They can also be used for studying the structure and organization of PT networks, as well as the accessibility and the level of service these networks provide. However, using raw GTFS data is challenging as researchers need to understand the details of the GTFS data format, make sure that the data contain all relevant modes of public transport, and have no errors. To lower the barrier for using GTFS data in research, we publish a curated collection of 25 cities' public transport networks in multiple easy-to-use formats including network edge lists, temporal network event lists, SQLite databases, GeoJSON files, and the GTFS data format. This collection promotes the study of how PT is organized across the globe, and also provides a testbed for developing tools for PT network analysis and PT routing algorithms.

Multichannel social signatures and persistent features of ego networks.

The structure of egocentric networks reflects the way people balance their need for strong, emotionally intense relationships and a diversity of weaker ties. Egocentric network structure can be quantified with 'social signatures', which describe how people distribute their communication effort across the members (alters) of their personal networks. Social signatures based on call data have indicated that people mostly communicate with a few close alters; they also have persistent, distinct signatures. To examine if these results hold for other channels of communication, here we compare social signatures built from call and text message data, and develop a way of constructing mixed social signatures using both channels. We observe that all types of signatures display persistent individual differences that remain stable despite the turnover in individual alters. We also show that call, text, and mixed signatures resemble one another both at the population level and at the level of individuals. The consistency of social signatures across individuals for different channels of communication is surprising because the choice of channel appears to be alter-specific with no clear overall pattern, and ego networks constructed from calls and texts overlap only partially in terms of alters. These results demonstrate individuals vary in how they allocate their communication effort across their personal networks and this variation is persistent over time and across different channels of communication.

Effects of spatial smoothing on functional brain networks.

Graph-theoretical methods have rapidly become a standard tool in studies of the structure and function of the human brain. Whereas the structural connectome can be fairly straightforwardly mapped onto a complex network, there are more degrees of freedom in constructing networks that represent functional connections between brain areas. For functional magnetic resonance imaging (fMRI) data, such networks are typically built by aggregating the blood-oxygen-level dependent signal time series of voxels into larger entities (such as Regions of Interest in some brain atlas) and determining their connection strengths from some measure of time-series correlations. Although it is evident that the outcome must be affected by how the voxel-level time series are treated at the preprocessing stage, there is a lack of systematic studies of the effects of preprocessing on network structure. Here, we focus on the effects of spatial smoothing, a standard preprocessing method for fMRI. We apply various levels of spatial smoothing to resting-state fMRI data and measure the changes induced in functional networks. We show that the level of spatial smoothing clearly affects the degrees and other centrality measures of functional network nodes; these changes are non-uniform, systematic, and depend on the geometry of the brain. The composition of the largest connected network component is also affected in a way that artificially increases the similarity of the networks of different subjects. Our conclusion is that wherever possible, spatial smoothing should be avoided when preprocessing fMRI data for network analysis.