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Register a new userAltered structural balance of resting-state networks in autism
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Z. Moradimanesh
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What makes a network complex, in addition to its size, is the interconnected interactions between elements, disruption of which inevitably results in dysfunction. Likewise, the brain networks complexity arises from interactions beyond pair connections, as it is simplistic to assume that in complex networks state of a link is independently determined only according to its two constituting nodes. This is particularly of note in genetically complex brain impairments, such as the autism spectrum disorder (ASD). Accordingly, structural balance theory (SBT) affirms that in the real-world signed networks, a link is remarkably influenced by each of its two nodes interactions with the third node within a triadic interrelationship. Thus, it is plausible to ask whether ASD is associated with altered structural balance resulting from atypical triadic interactions. In other words, it is the abnormal interplay of positive and negative interactions that matter in ASD, besides and beyond hypo (hyper) pair connectivity. To address this, we explore triadic interactions in the rs-fMRI network of participants with ASD relative to healthy controls (CON). We demonstrate that balanced triads are overrepresented in the ASD and CON networks while unbalanced triads are underrepresented, providing first-time empirical evidence for the strong notion of structural balance on the brain networks. We further analyze the frequency and energy distribution of triads and suggest an alternative description for the reduced functional integration and segregation in the ASD brain networks. Last but not least, we observe that energy of the salient and the default mode networks are lower in autism, which may be a reflection of the difficulty in flexible behaviors. Altogether, these results highlight the potential value of SBT as a new perspective in functional connectivity studies, especially in neurodevelopmental disorders.
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Autism spectrum disorder (ASD) is one of the major developmental disorders affecting children. Recently, it has been hypothesized that ASD is associated with atypical brain connectivities. A substantial body of researches use Pearsons correlation coefficients, mutual information, or partial correlation to investigate the differences in brain connectivities between ASD and typical controls from functional Magnetic Resonance Imaging (fMRI). However, correlation or partial correlation does not directly reveal causal influences - the information flow - between brain regions. Comparing to correlation, causality pinpoints the key connectivity characteristics and removes redundant features for diagnosis. In this paper, we propose a two-step method for large-scale and cyclic causal discovery from fMRI. It can identify brain causal structures without doing interventional experiments. The learned causal structure, as well as the causal influence strength, provides us the path and effectiveness of information flow. With the recovered causal influence strength as candidate features, we then perform ASD diagnosis by further doing feature selection and classification. We apply our methods to three datasets from Autism Brain Imaging Data Exchange (ABIDE). From experimental results, it shows that with causal connectivities, the diagnostic accuracy largely improves. A closer examination shows that information flows starting from the superior front gyrus to default mode network and posterior areas are largely reduced. Moreover, all enhanced information flows are from posterior to anterior or in local areas. Overall, it shows that long-range influences have a larger proportion of reductions than local ones, while local influences have a larger proportion of increases than long-range ones. By examining the graph properties of brain causal structure, the group of ASD shows reduced small-worldness.
Diverse cognitive processes set different demands on locally segregated and globally integrated brain activity. However, it remains unclear how resting brains configure their functional organization to balance the demands on network segregation and integration to best serve cognition. Here, we use an eigenmode-based approach to identify hierarchical modules in functional brain networks, and quantify the functional balance between network segregation and integration. In a large sample of healthy young adults (n=991), we combine the whole-brain resting state functional magnetic resonance imaging (fMRI) data with a mean-filed model on the structural network derived from diffusion tensor imaging and demonstrate that resting brain networks are on average close to a balanced state. This state allows for a balanced time dwelling at segregated and integrated configurations, and highly flexible switching between them. Furthermore, we employ structural equation modelling to estimate general and domain-specific cognitive phenotypes from nine tasks, and demonstrate that network segregation, integration and their balance in resting brains predict individual differences in diverse cognitive phenotypes. More specifically, stronger integration is associated with better general cognitive ability, stronger segregation fosters crystallized intelligence and processing speed, and individuals tendency towards balance supports better memory. Our findings provide a comprehensive and deep understanding of the brains functioning principles in supporting diverse functional demands and cognitive abilities, and advance modern network neuroscience theories of human cognition.
Attention-deficit/hyperactivity disorder (ADHD) is increasingly being diagnosed in adults, but the neural mechanisms underlying its distinct clinical symptoms (hyperactivity and inattention) remain poorly understood. Here, we used a nested-spectral partition approach to study resting-state brain networks for ADHD patients and healthy adults and adopted hierarchical segregation and integration to predict clinical symptoms. Adult ADHD is typically characterized by an overintegrated interaction within default mode network. Limbic system is dominantly affected by ADHD and has an earlier aging functional pattern, but salient attention system is preferably affected by age and shows an opposite aging trajectory. More importantly, these two systems selectively and robustly predict distinct ADHD symptoms. Earlier-aging limbic system prefers to predict hyperactivity, and age-affected salient attention system better predicts inattention. Our findings provide a more comprehensive and deeper understanding of the neural basis of distinct ADHD symptoms and could contribute to the development of more objective clinical diagnoses.
Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality-metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distortion of signal dynamics. Instead, the phantom showed that dynamic fidelity is reasonably approximated by a measure that, unlike tSNR, dissociates signal dynamics from scanner artifact. We then tested this measure, signal fluctuation sensitivity (SFS), against human resting-state data. As predicted by the phantom, SFS--and not tSNR--is associated with enhanced sensitivity to both local and long-range connectivity within the brains default mode network.
Long-range temporal coherence (LRTC) is quite common to dynamic systems and is fundamental to the system function. LRTC in the brain has been shown to be important to cognition. Assessing LRTC may provide critical information for understanding the potential underpinnings of brain organization, function, and cognition. To facilitate this overarching goal, we provide a method, which is named temporal coherence mapping (TCM), to explicitly quantify LRTC using resting state fMRI. TCM is based on correlation analysis of the transit states of the phase space reconstructed by temporal embedding. A few TCM properties were collected to measure LRTC, including the averaged correlation, anti-correlation, the ratio of correlation and anticorrelation, the mean coherent and incoherent duration, and the ratio between the coherent and incoherent time. TCM was first evaluated with simulations and then with the large Human Connectome Project data. Evaluation results showed that TCM metrics can successfully differentiate signals with different temporal coherence regardless of the parameters used to reconstruct the phase space. In human brain, TCM metrics except the ratio of the coherent/incoherent time showed high test-retest reproducibility; TCM metrics are related to age, sex, and total cognitive scores. In summary, TCM provides a first-of-its-kind tool to assess LRTC and the imbalance between coherence and incoherence; TCM properties are physiologically and cognitively meaningful.
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