Statistical testing and annotation of gene transcriptomic-neuroimaging associations

AbstractMultiscale integration of neuroimaging and gene transcriptome is becoming a widely used approach for exploring the molecular pathways of brain structure and function, in health and disease. Statistical testing of associations between spatial patterns of imaging-based phenotypic and transcriptomic data is key in these explorations, in particular establishing that observed associations exceed ‘chance level’ of random, non-specific observations. We discuss options for such statistical evaluations, including commonly applied linear regression, null model based on randomized brain regions that maintain spatial relationships, and null models built upon random effects that occur from other genes. Using examples and simulations of analyses as commonly performed in literature, we explain the caveats of these statistical models and provide guidelines for using proper models to evaluate both spatial and gene specificity. The null models are presented in a web-based application called GAMBA (“Gene Annotation using Macroscale Brain-imaging Association”) that is designed for exploring transcriptomic-neuroimaging associations.

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Olfactory Loss and Regain: Lessons for Neuroplasticity

The Neuroscientist ◽

10.1177/1073858417703910 ◽

2017 ◽

Vol 24 (1) ◽

pp. 22-35 ◽

Cited By ~ 15

Author(s):

Johanna L. Reichert ◽

Veronika Schöpf

Keyword(s):

Structural Changes ◽

Brain Regions ◽

Sensory Loss ◽

Trigeminal System ◽

Olfactory Loss ◽

Brain Structure And Function ◽

Olfactory Sense ◽

Neuronal Reorganization ◽

Functional Neuroplasticity ◽

And Function

For the visual and auditory senses, an array of studies has reported on neuronal reorganization processes after sensory loss. In contrast to this, neuroplasticity has been investigated only scarcely after loss of the olfactory sense. The present review focuses on the current extent of literature on structural and functional neuroplasticity effects after loss, with a focus on magnetic resonance imaging–based studies. We also include findings on the regain of the olfactory sense, for example after successful olfactory training. Existing studies indicate that widespread structural changes beyond the level of the olfactory bulb occur in the brain after loss of the olfactory sense. Moreover, on a functional level, loss of olfactory input not only entails changes in olfaction-related brain regions but also in the trigeminal system. Existing evidence should be strengthened by future longitudinal studies, a more thorough investigation of the neuronal consequences of congenital anosmia, and the application of state-of-the-art neuroimaging methods, such as connectivity analyses and joint analyses of brain structure and function.

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Gradients of structure–function tethering across neocortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1903403116 ◽

2019 ◽

Vol 116 (42) ◽

pp. 21219-21227 ◽

Cited By ~ 78

Author(s):

Bertha Vázquez-Rodríguez ◽

Laura E. Suárez ◽

Ross D. Markello ◽

Golia Shafiei ◽

Casey Paquola ◽

...

Keyword(s):

Structure Function ◽

Present Report ◽

Brain Regions ◽

Structure And Function ◽

Spatial Proximity ◽

Functional Networks ◽

Functional Connection ◽

Brain Structure And Function ◽

And Function ◽

The Brain

The white matter architecture of the brain imparts a distinct signature on neuronal coactivation patterns. Interregional projections promote synchrony among distant neuronal populations, giving rise to richly patterned functional networks. A variety of statistical, communication, and biophysical models have been proposed to study the relationship between brain structure and function, but the link is not yet known. In the present report we seek to relate the structural and functional connection profiles of individual brain areas. We apply a simple multilinear model that incorporates information about spatial proximity, routing, and diffusion between brain regions to predict their functional connectivity. We find that structure–function relationships vary markedly across the neocortex. Structure and function correspond closely in unimodal, primary sensory, and motor regions, but diverge in transmodal cortex, particularly the default mode and salience networks. The divergence between structure and function systematically follows functional and cytoarchitectonic hierarchies. Altogether, the present results demonstrate that structural and functional networks do not align uniformly across the brain, but gradually uncouple in higher-order polysensory areas.

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Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

International Journal of Molecular Sciences ◽

10.3390/ijms23010305 ◽

2021 ◽

Vol 23 (1) ◽

pp. 305

Author(s):

Eunsoo Won ◽

Kyoung-Sae Na ◽

Yong-Ku Kim

Keyword(s):

Emotional Regulation ◽

Inflammatory Responses ◽

Underlying Mechanism ◽

Brain Regions ◽

Immune Markers ◽

Inflammatory Conditions ◽

Brain Structure And Function ◽

Immune System Regulation ◽

And Function ◽

The Brain

Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers.

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Effects of computer gaming on cognition, brain structure, and function: a critical reflection on existing literature

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2019.21.3/skuehn ◽

2019 ◽

Vol 21 (3) ◽

pp. 319-330 ◽

Cited By ~ 2

Keyword(s):

Structural Changes ◽

Leisure Activity ◽

Theoretical Work ◽

Brain Regions ◽

Video Gaming ◽

Computer Gaming ◽

Cognitive Changes ◽

Study Protocols ◽

Brain Structure And Function ◽

And Function

Video gaming as a popular form of leisure activity and its effect on cognition, brain function, and structure has come into focus in the field of neuroscience. Visuospatial cognition and attention seem to benefit the most, whereas for executive functions, memory, and general cognition, the results are contradictory. The particular characteristics of video games driving these effects remain poorly understood. We critically discuss major challenges for the existing research, namely, the lack of precise definitions of video gaming, the lack of distinct choice of cognitive ability under study, and the lack of standardized study protocols. Less research exists on neural changes in addition to cognitive changes due to video gaming. Existing studies reveal evidence for the involvement of similar brain regions in functional and structural changes. There seems to be a predominance in the hippocampal, prefrontal, and parietal brain regions; however, studies differ immensely, which makes a meta-analytic interpretation vulnerable. We conclude that theoretical work is urgently needed.

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Cortex-wide neural interfacing via transparent polymer skulls

10.1101/387142 ◽

2018 ◽

Author(s):

Leila Ghanbari ◽

Russell E. Carter ◽

Matthew L. Rynes ◽

Judith Dominguez ◽

Gang Chen ◽

...

Keyword(s):

Neural Activity ◽

Brain Regions ◽

Two Photon ◽

Neural Activities ◽

Neural Computations ◽

Brain Structure And Function ◽

Cortical Regions ◽

And Function ◽

Subcellular Resolution

ABSTRACTNeural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating cognition, perception and sensorimotor behaviors. Enormous progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. To fill this need, we have engineered “See-Shells” – digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>200 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm through the See-Shells. See-Shells implanted on transgenic mice expressing genetically encoded calcium (Ca2+) indicators allow tracking of neural activities from multiple, non-contiguous regions spread across millimeters of the cortex. Further, neural probes can access the brain through perforated See-Shells, either for perturbing or recording neural activity from localized brain regions simultaneously with whole cortex imaging. As See-Shells can be constructed using readily available desktop fabrication tools and modified to fit a range of skull geometries, they provide a powerful tool for investigating brain structure and function.

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Desikan-Killiany-Tourville Atlas Compatible Version of M-CRIB Neonatal Parcellated Whole Brain Atlas: The M-CRIB 2.0

10.1101/409045 ◽

2018 ◽

Cited By ~ 1

Author(s):

Bonnie Alexander ◽

Wai Yen Loh ◽

Lillian G. Matthews ◽

Andrea L. Murray ◽

Chris Adamson ◽

...

Keyword(s):

Brain Regions ◽

Brain Atlas ◽

Whole Brain ◽

Brain Structure And Function ◽

Postmenstrual Age ◽

Mri Scans ◽

Subcortical Regions ◽

Cortical Regions ◽

And Function ◽

Ventral Diencephalon

AbstractOur recently published M-CRIB atlas comprises 100 neonatal brain regions including 68 compatible with the widely-used Desikan-Killiany adult cortical atlas. A successor to the Desikan-Killiany atlas is the Desikan-Killiany-Tourville atlas, in which some regions with unclear boundaries were removed, and many existing boundaries were revised to conform to clearer landmarks in sulcal fundi. Our first aim here was to modify cortical M-CRIB regions to comply with the Desikan-Killiany-Tourville protocol, in order to offer: a) compatibility with this adult cortical atlas, b) greater labelling accuracy due to clearer landmarks, and c) optimisation of cortical regions for integration with surface-based infant parcellation pipelines. Secondly, we aimed to update subcortical regions in order to offer greater compatibility with subcortical segmentations produced in FreeSurfer. Data utilized were the T2-weighted MRI scans in our M-CRIB atlas, for ten healthy neonates (postmenstrual age at MRI 40-43 weeks, 4 female), and corresponding parcellated images. Edits were performed on the parcellated images in volume space using ITK-SNAP. Cortical updates included deletion of frontal and temporal poles and ‘Banks STS’, and modification of boundaries of many other regions. Changes to subcortical regions included the addition of ‘ventral diencephalon’, and deletion of ‘subcortical matter’ labels. A detailed updated parcellation protocol was produced. The resulting whole-brain M-CRIB 2.0 atlas comprises 94 regions altogether. This atlas provides comparability with adult Desikan-Killiany-Tourville-labelled cortical data and FreeSurfer-labelled subcortical data, and is more readily adaptable for incorporation into surface-based neonatal parcellation pipelines. As such, it offers the ability to help facilitate a broad range of investigations into brain structure and function both at the neonatal time point and developmentally across the lifespan.

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Neural Basis of Apathy

10.1093/med/9780198841807.003.0010 ◽

2021 ◽

pp. 174-190

Author(s):

Ingrid Agartz ◽

Lynn Mørch-Johnsen

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Brain Regions ◽

Anterior Cingulate ◽

Resonance Imaging ◽

Neural Basis ◽

Positron Emission ◽

White Matter Microstructure ◽

Brain Structure And Function ◽

And Function

This chapter introduces structural neuroimaging methods and presents results from brain imaging studies of the clinical apathy syndrome in neurodegenerative diseases such as Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, Huntington’s disease, and stroke, and also in schizophrenia, today considered a neurodevelopmental disease. The main method used has been magnetic resonance imaging, which also holds many innovative possibilities for future development. Scientific studies so far have pointed to structural differences in frontal, striatal, anterior cingulate, and parietal brain regions, and of white matter microstructure and connectivity changes as being involved in the apathy syndrome. No single circuit connected to apathy has so far been identified. Brain structure and function, studied at the systems network level, and integrative multimodal imaging approaches, which combine different high-resolution magnetic resonance imaging, magnetic resonance diffusion, and positron emission tomography techniques, can be helpful in resolving future questions.

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Major Depressive Disorder in Neuroimaging: What is Beyond Fronto-limbic Model?

Current Psychiatry Research and Reviews ◽

10.2174/1573400515666181213155225 ◽

2019 ◽

Vol 15 (1) ◽

pp. 37-43

Author(s):

Chien-Han Lai

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Clinical Symptoms ◽

Brain Regions ◽

Major Depressive ◽

Limbic Structures ◽

Emotional Memories ◽

Brain Structure And Function ◽

In The Beginning ◽

And Function

Background: The major depressive disorder (MDD) is a chronic illness with major manifestations in cognitive, social and occupational functions. The pathophysiological model is an intrigue issue for scientists to understand the origin of MDD. Objective: In the beginning, the cortico-limbic-striato-pallidal-thalamic model has been proposed to link the clinical symptoms with the abnormalities in brain structure and function. However, the model is still evolving due to recent advances in the neuroimaging techniques, especially for functional magnetic resonance imaging (fMRI). The recent findings in the fMRI studies in MDD showed the importance of fronto-limbic model for the modulations between cognitive function and primitive and negative emotions. Method: This review will focus on the literature of fMRI studies in MDD with findings not in the fronto-limbic structures. Results: Additional regions beyond the fronto-limbic model have been observed in some literature of MDD. Some regions in the parietal, temporal and occipital lobes have been shown with the alterations in gray matter, white matter and brain function. The importance of sensory detection, visuospatial function, language reception, motor response and emotional memories in these regions might provide the clues to understand the cognitive misinterpretations related to altered reception of outside information, behavioral responses related to biased cognition and emotional memories and clinical symptoms related to the significant alterations of interactions between different brain regions. Conclusion: Future studies to establish a more comprehensive model for MDD will be warranted, especially for the model beyond the fronto-limbic structures.

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The gut microbiome is associated with brain structure and function in schizophrenia

Scientific Reports ◽

10.1038/s41598-021-89166-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shijia Li ◽

Jie Song ◽

Pengfei Ke ◽

Lingyin Kong ◽

Bingye Lei ◽

...

Keyword(s):

Gut Microbiome ◽

Brain Structure ◽

Gray Matter Volume ◽

Low Frequency ◽

Alpha Diversity ◽

Brain Regions ◽

Structure And Function ◽

Brain Structure And Function ◽

The Right ◽

And Function

AbstractThe effect of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we used 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZ) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was significantly higher in SZ patients than in NCs. Additionally, the analysis of MRI data revealed that several brain regions showed significantly lower gray matter volume (GMV) and regional homogeneity (ReHo) but significantly higher amplitude of low-frequency fluctuation in SZ patients than in NCs. Moreover, the alpha diversity of the gut microbiota showed a strong linear relationship with the values of both GMV and ReHo. In SZ patients, the ReHo indexes in the right STC (r = − 0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = − 0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = − 0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with the abundance of the genus Roseburia. Our results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function. This study provides insights into the underlying neuropathology of SZ.

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Exercise, Fitness and the Aging Brain: A Review of Functional Connectivity in Aging

Archives of Psychology ◽

10.31296/aop.v3i4.98 ◽

2019 ◽

Vol 3 (4) ◽

Cited By ~ 8

Author(s):

Chelsea M. Stillman ◽

Shannon D. Donofry ◽

Kirk I. Erickson

Keyword(s):

Physical Activity ◽

Functional Connectivity ◽

Brain Structure ◽

Late Life ◽

Brain Regions ◽

Structure And Function ◽

Global Changes ◽

Age Related ◽

Brain Structure And Function ◽

And Function

Aging is associated with changes in brain structure and function with some brain regions showing more age-related deterioration than others. There is evidence that regional changes in brain structure and function may affect the functioning of other, less- age-sensitive brain regions and lead to more global changes in brain efficiency and cognitive functioning. Fortunately, emerging evidence from health neuroscience suggests that age-related brain changes and associated cognitive declines may not be inevitable. In fact, they may even be reversible. Exercise is a particularly promising health behavior known to induce changes in regional brain structure and function in older adults. However, much less is known about how exercise affects the organization of brain networks in late life. The purpose of this review is to summarize what is known to date regarding the relationships between functional connectivity, exercise, fitness, and physical activity in aging. A critical summary of this literature may reveal novel mechanisms by which physical activity influences brain health, which in turn may be leveraged to improve other aspects of functioning, including physical, cognitive, and mental health in late life.

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