Lisa Byrge

Changes in structural and functional connectivity among resting-state networks across the human lifespan

At rest, the brains sensorimotor and higher cognitive systems engage in organized patterns of correlated activity forming resting-state networks. An important empirical question is how functional connectivity and structural connectivity within and between resting-state networks change with age. In this study we use network modeling techniques to identify significant changes in network organization across the human lifespan. The results of this study demonstrate that whole-brain functional and structural connectivity both exhibit reorganization with age. On average, functional connections within resting-state networks weaken in magnitude while connections between resting-state networks tend to increase. These changes can be localized to a small subset of functional connections that exhibit systematic changes across the lifespan. Collectively, changes in functional connectivity are also manifest at a system-wide level, as components of the control, default mode, saliency/ventral attention, dorsal attention, and visual networks become less functionally cohesive, as evidenced by decreased component modularity. Paralleling this functional reorganization is a decrease in the density and weight of anatomical white-matter connections. Hub regions are particularly affected by these changes, and the capacity of those regions to communicate with other regions exhibits a lifelong pattern of decline. Finally, the relationship between functional connectivity and structural connectivity also appears to change with age; functional connectivity along multi-step structural paths tends to be stronger in older subjects than in younger subjects. Overall, our analysis points to age-related changes in inter-regional communication unfolding within and between resting-state networks.

Developmental process emerges from extended brain–body–behavior networks

Studies of brain connectivity have focused on two modes of networks: structural networks describing neuroanatomy and the intrinsic and evoked dependencies of functional networks at rest and during tasks. Each mode constrains and shapes the other across multiple timescales and each also shows age-related changes. Here we argue that understanding how brains change across development requires understanding the interplay between behavior and brain networks: changing bodies and activities modify the statistics of inputs to the brain; these changing inputs mold brain networks; and these networks, in turn, promote further change in behavior and input.

Idiosyncratic Brain Activation Patterns Are Associated with Poor Social Comprehension in Autism

Autism spectrum disorder (ASD) features profound social deficits but neuroimaging studies have failed to find any consistent neural signature. Here we connect these two facts by showing that idiosyncratic patterns of brain activation are associated with social comprehension deficits. Human participants with ASD (N = 17) and controls (N = 20) freely watched a television situation comedy (sitcom) depicting seminaturalistic social interactions (“The Office”, NBC Universal) in the scanner. Intersubject correlations in the pattern of evoked brain activation were reduced in the ASD group—but this effect was driven entirely by five ASD subjects whose idiosyncratic responses were also internally unreliable. The idiosyncrasy of these five ASD subjects was not explained by detailed neuropsychological profile, eye movements, or data quality; however, they were specifically impaired in understanding the social motivations of characters in the sitcom. Brain activation patterns in the remaining ASD subjects were indistinguishable from those of control subjects using multiple multivariate approaches. Our findings link neurofunctional abnormalities evoked by seminaturalistic stimuli with a specific impairment in social comprehension, and highlight the need to conceive of ASD as a heterogeneous classification.

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.

Identifying and characterizing systematic temporally-lagged BOLD artifacts

&NA; Residual noise in the BOLD signal remains problematic for fMRI – particularly for techniques such as functional connectivity, where findings can be spuriously influenced by noise sources that can covary with individual differences. Many such potential noise sources – for instance, motion and respiration – can have a temporally lagged effect on the BOLD signal. Thus, here we present a tool for assessing residual lagged structure in the BOLD signal that is associated with nuisance signals, using a construction similar to a peri‐event time histogram. Using this method, we find that framewise displacements – both large and very small – were followed by structured, prolonged, and global changes in the BOLD signal that depend on the magnitude of the preceding displacement and extend for tens of seconds. This residual lagged BOLD structure was consistent across datasets, and independently predicted considerable variance in the global cortical signal (as much as 30–40% in some subjects). Mean functional connectivity estimates varied similarly as a function of displacements occurring many seconds in the past, even after strict censoring. Similar patterns of residual lagged BOLD structure were apparent following respiratory fluctuations (which covaried with framewise displacements), implicating respiration as one likely mechanism underlying the displacement‐linked structure observed. Global signal regression largely attenuates this artifactual structure. These findings suggest the need for caution in interpreting results of individual difference studies where noise sources might covary with the individual differences of interest, and highlight the need for further development of preprocessing techniques for mitigating such structure in a more nuanced and targeted manner. HighlightsIntroduces an approach for revealing residual lagged structure in the BOLD signal.Reveals robust, predictable artifact; linked with variation in mean FC.Artifact follows large & small displacements and is linked with respiration.Global signal regression eliminates artifact, helping to avoid spurious conclusions.A MATLAB script for general data exploration & quality assessment is provided.

High-accuracy individual identification using a “thin slice” of the functional connectome

Connectome fingerprinting—a method that uses many thousands of functional connections in aggregate to identify individuals—holds promise for individualized neuroimaging. A better characterization of the features underlying successful fingerprinting performance—how many and which functional connections are necessary and/or sufficient for high accuracy—will further inform our understanding of uniqueness in brain functioning. Thus, here we examine the limits of high-accuracy individual identification from functional connectomes. Using ∼3,300 scans from the Human Connectome Project in a split-half design and an independent replication sample, we find that a remarkably small “thin slice” of the connectome—as few as 40 out of 64,620 functional connections—was sufficient to uniquely identify individuals. Yet, we find that no specific connections or even specific networks were necessary for identification, as even small random samples of the connectome were sufficient. These results have important conceptual and practical implications for the manifestation and detection of uniqueness in the brain. Author Summary Patterns of functional connectivity are so distinct between different people that they can be used to predict individual identity with high accuracy. Here, we show that a strikingly small fraction of the functional connectome is actually needed to predict individual identity (as few as 40 functional connections from 64,620). We further show that although certain functional connections may be most informative, even small fractions of the connectome selected at random can be used to identify individuals, and that no specific connections or even networks are actually necessary. The results indicate that uniquely identifying signatures of brain functioning are widely distributed throughout the brain and can be detected in a much more compact manner than previously appreciated.