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Decoupling of brain function from structure reveals regional behavioral specialization in humans.

ABSTRACT: The brain is an assembly of neuronal populations interconnected by structural pathways. Brain activity is expressed on and constrained by this substrate. Therefore, statistical dependencies between functional signals in directly connected areas can be expected higher. However, the degree to which brain function is bound by the underlying wiring diagram remains a complex question that has been only partially answered. Here, we introduce the structural-decoupling index to quantify the coupling strength between structure and function, and we reveal a macroscale gradient from brain regions more strongly coupled, to regions more strongly decoupled, than expected by realistic surrogate data. This gradient spans behavioral domains from lower-level sensory function to high-level cognitive ones and shows for the first time that the strength of structure-function coupling is spatially varying in line with evidence derived from other modalities, such as functional connectivity, gene expression, microstructural properties and temporal hierarchy.

SUBMITTER: Preti MG

PROVIDER: S-EPMC6800438 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Decoupling of brain function from structure reveals regional behavioral specialization in humans.

Preti Maria Giulia MG Van De Ville Dimitri D

Nature communications 20191018 1

The brain is an assembly of neuronal populations interconnected by structural pathways. Brain activity is expressed on and constrained by this substrate. Therefore, statistical dependencies between functional signals in directly connected areas can be expected higher. However, the degree to which brain function is bound by the underlying wiring diagram remains a complex question that has been only partially answered. Here, we introduce the structural-decoupling index to quantify the coupling str ...[more]

PMID: 31628329

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Project description:Functional signals emerge from the structural network, supporting multiple cognitive processes through underlying molecular mechanism. The link between human brain structure and function is region-specific and hierarchical across the neocortex. However, the relationship between hierarchical structure-function decoupling and the manifestation of individual behavior and cognition, along with the significance of the functional systems involved, and the specific molecular mechanism underlying structure-function decoupling remain incompletely characterized. Here, we used the structural-decoupling index (SDI) to quantify the dependency of functional signals on the structural connectome using a significantly larger cohort of healthy subjects. Canonical correlation analysis (CCA) was utilized to assess the general multivariate correlation pattern between region-specific SDIs across the whole brain and multiple cognitive traits. Then, we predicted five composite cognitive scores resulting from multivariate analysis using SDIs in primary networks, association networks, and all networks, respectively. Finally, we explored the molecular mechanism related to SDI by investigating its genetic factors and relationship with neurotransmitter receptors/transporters. We demonstrated that structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. We revealed better performance in cognition prediction is achieved by using high-level hierarchical SDIs, with varying significance of different brain regions in predicting cognitive processes. We found that the SDIs were associated with the gene expression level of several receptor-related terms, and we also found the spatial distributions of four receptors/transporters significantly correlated with SDIs, namely D2, NET, MOR, and mGluR5, which play an important role in the flexibility of neuronal function. Collectively, our findings corroborate the association between hierarchical macroscale structure-function decoupling and individual cognition and provide implications for comprehending the molecular mechanism of structure-function decoupling. PRACTITIONER POINTS: Structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. High-level hierarchical structure-function decoupling contributes much more than low-level decoupling to individual cognition. Structure-function decoupling could be regulated by genes associated with pivotal receptors that are crucial for neuronal function flexibility.

Project description:BackgroundThe mammalian brain is organized into regions with specific biological functions and properties. These regions have distinct transcriptomes, but little is known whether they may also differ in their metabolome. The metabolome, a collection of small molecules or metabolites, is at the intersection of the genetic background of a given cell or tissue and the environmental influences that affect it. Thus, the metabolome directly reflects information about the physiologic state of a biological system under a particular condition. The objective of this study was to investigate whether various brain regions have diverse metabolome profiles, similarly to their genetic diversity. The answer to this question would suggest that not only the genome but also the metabolome may contribute to the functional diversity of brain regions.MethodsWe investigated the metabolome of four regions of the mouse brain that have very distinct functions: frontal cortex, hippocampus, cerebellum, and olfactory bulb. We utilized gas- and liquid- chromatography mass spectrometry platforms and identified 215 metabolites.ResultsPrincipal component analysis, an unsupervised multivariate analysis, clustered each brain region based on its metabolome content, thus providing the unique metabolic profile of each region. A pathway-centric analysis indicated that olfactory bulb and cerebellum had most distinct metabolic profiles, while the cortical parenchyma and hippocampus were more similar in their metabolome content. Among the notable differences were distinct oxidative-anti-oxidative status and region-specific lipid profiles. Finally, a global metabolic connectivity analysis using the weighted correlation network analysis identified five hub metabolites that organized a unique metabolic network architecture within each examined brain region. These data indicate the diversity of global metabolome corresponding to specialized regional brain function and provide a new perspective on the underlying properties of brain regions.ConclusionIn summary, we observed many differences in the metabolome among the various brain regions investigated. All four brain regions in our study had a unique metabolic signature, but the metabolites came from all categories and were not pathway-centric.

Project description:Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1). Previous studies in mice and humans suggested that GHRD has protective effects against age-related diseases, including cancer and diabetes. Whereas GHRD mice show improved age-dependent cognitive performance, the effect of GHRD on human cognition remains unknown. Using MRI, we compared brain structure, function, and connectivity between 13 people with GHRD and 12 unaffected relatives. We assessed differences in white matter microstructural integrity, hippocampal volume, subregional volumes, and cortical thickness and surface area of selected regions. We also evaluated brain activity at rest and during a hippocampal-dependent pattern separation task. The GHRD group had larger surface areas in several frontal and cingulate regions and showed trends toward larger dentate gyrus and CA1 regions of the hippocampus. They had lower mean diffusivity in the genu of the corpus callosum and the anterior thalamic tracts. The GHRD group showed enhanced cognitive performance and greater task-related activation in frontal, parietal, and hippocampal regions compared with controls. Furthermore, they had greater functional synchronicity of activity between the precuneus and the rest of the default mode network at rest. The results suggest that, compared with controls, GHRD subjects have brain structure and function that are more consistent with those observed in younger adults reported in previous studies. Further investigation may lead to improved understanding of underlying mechanisms and could contribute to the identification of treatments for age-related cognitive deficits.SIGNIFICANCE STATEMENT People and mice with growth hormone receptor deficiency (GHRD or Laron syndrome) are protected against age-related diseases including cancer and diabetes. However, in humans, it is unknown whether cognitive function and brain structure are affected by GHRD. Using MRI, we examined cognition in an Ecuadorian population with GHRD and their unaffected relatives. The GHRD group showed better memory performance than their relatives. The differences in brain structure and function that we saw between the two groups were not consistent with variations typically associated with brain deficits. This study contributes to our understanding of the connection between growth genes and brain aging in humans and provides data indicating that GHR inhibition has the potential to protect against age-dependent cognitive decline.

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Decoupling of brain function from structure reveals regional behavioral specialization in humans.

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Decoupling of brain function from structure reveals regional behavioral specialization in humans.

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