Siyuan Liu

Siyuan Liu
U.S. Department of Health and Human Services | HHS · National Institutes of Health (NIH)

Doctor of Philosophy

About

63
Publications
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Publications

Publications (63)
Preprint
The human cerebral cortex underlies many of our unique strengths and vulnerabilities as a species - but efforts to understand its organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding or functional activation are accessed through spatially dense neuroima...
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The X-chromosome has long been hypothesized to have a disproportionate influence on the brain based on its enrichment for genes that are expressed in the brain and associated with intellectual disability. Here, we verify this hypothesis through partitioned heritability analysis of X-chromosome influences (XIs) on human brain anatomy in 32,256 indiv...
Article
Anatomical organization of the primate cortex varies as a function of total brain size, where possession of a larger brain is accompanied by disproportionate expansion of associative cortices alongside a relative contraction of sensorimotor systems. However, equivalent scaling maps are not yet available for regional white matter anatomy. Here, we u...
Article
Sex chromosome aneuploidies, a group of neurogenetic conditions characterized by aberrant sex chromosome dosage (SCD), are associated with increased risks for psychopathology as well as alterations in gray matter structure. However, we still lack a comprehensive understanding of potential SCD-associated changes in white matter structure, or knowled...
Article
Klinefelter syndrome (47, XXY; henceforth: XXY syndrome) is a high-impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first study to map alterations of functional brain connectivity in XXY syndrome and relate these changes to brain anatomy and psychopathology. We used resting-state functional magn...
Article
Brain structural covariance norms capture the coordination of neurodevelopmental programs between different brain regions. We develop and apply anatomical imbalance mapping (AIM), a method to measure and model individual deviations from these norms, to provide a lifespan map of morphological integration in the human cortex. In cross-sectional and l...
Preprint
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Klinefelter syndrome (47, XXY; Henceforth: XXY syndrome) is a high impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first neuroimaging study to map resting-state functional connectivity (rsFC) changes in XXY syndrome and ask how these might relate to brain anatomy and psychopathology. We collect...
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Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
The mechanisms underlying cortical folding are incompletely understood. Prior studies have suggested that individual differences in sulcal depth are genetically mediated, with deeper and ontologically older sulci more heritable than others. In this study, we examine FreeSurfer-derived estimates of average convexity and mean curvature as proxy measu...
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Humans display reproducible sex differences in cognition and behavior, which may partly reflect intrinsic sex differences in regional brain organization. However, the consistency, causes and consequences of sex differences in the human brain are poorly characterized and hotly debated. In contrast, recent studies in mice—a major model organism for s...
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Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental di...
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Sex chromosome aneuploidy (SCA) increases the risk for cognitive deficits, and confers changes in regional cortical thickness (CT) and surface area (SA). Neuroanatomical correlates of inter‐individual variation in cognitive ability have been described in health, but are not well‐characterized in SCA. Here, we modeled relationships between general c...
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Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical stu...
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Sex chromosome dosage (SCD) variation increases risk for neuropsychiatric impairment, which may reflect direct SCD effects on brain organization. Here, we 1) map cumulative X- and Y-chromosome dosage effects on regional cortical thickness (CT) and investigate potential functional implications of these effects using Neurosynth, 2) test if this map i...
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The cerebral cortex contains a significant quantity of intracortical myelin, but the genetics of cortical myelination (CM) in humans is not well understood. Relatively novel MRI-derived measures now enable the investigation of cortical myelination in large samples. In this study, we use a genetically-informative neuroimaging sample of 1096 young ad...
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Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the gene...
Preprint
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Neurodevelopmental disorders are highly heritable and associated with spatially-selective disruptions of brain anatomy. The logic that translates genetic risks into spatially patterned brain vulnerabilities remains unclear but is a fundamental question in disease pathogenesis. Here, we approach this question by integrating (i) in vivo neuroimaging...
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The genetics of cortical arealization in youth is not well understood. In this study, we use a genetically informative sample of 677 typically developing children and adolescents (mean age 12.72 years), high-resolution MRI, and quantitative genetic methodology to address several fundamental questions on the genetics of cerebral surface area. We est...
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Conversation is an important and ubiquitous social behavior. Individuals with Autism Spectrum Disorder (autism) without intellectual disability often have normal structural language abilities but deficits in social aspects of communication like pragmatics, prosody, and eye contact. Previous studies of resting state activity suggest that intrinsic c...
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Childhood socioeconomic status (SES) impacts cognitive development and mental health, but its association with human structural brain development is not yet well characterized. Here, we analyzed 1243 longitudinally acquired structural MRI scans from 623 youth (299 female/324 male) to investigate the relation between SES and cortical and subcortical...
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The hippocampus exhibits striking volume reductions in schizophrenia (van Erp et al., 2016), with regionally specific changes in subfields cornu ammonis 1 to 4 (CA1-4), dentate gyrus, and subiculum (Mathew et al., 2014). Models of hippocampal function suggest an association with memory deficits in schizophrenia patients; for example, impairment of...
Preprint
Full-text available
Childhood socioeconomic status (SES) impacts cognitive development and mental health, but its association with structural brain development is not yet well-characterized. Here, we analyzed 1243 longitudinally-acquired structural MRI scans from 623 youth to investigate the relation between SES and cortical and subcortical morphology between ages 5 a...
Article
A critical issue in many neuroimaging studies is the comparison between brain maps. Nonetheless, it remains unclear how one should test hypotheses focused on the overlap or spatial correspondence between two or more brain maps. This "correspondence problem" affects, for example, the interpretation of comparisons between task-based patterns of funct...
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Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary more than twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 30...
Preprint
Full-text available
Conversation is an important and ubiquitous social behavior. Individuals with Autism Spectrum Disorder (autism) without intellectual disability often have normal language abilities but deficits in social aspects of verbal interaction like pragmatics, prosody, and eye contact. Previous studies of resting state activity suggest that intrinsic connect...
Article
Full-text available
Background: Childhood-onset schizophrenia (COS) is a rare, severe form of the adult-onset disorder (AOS). Our previous resting-state fMRI study identified attenuated functional connectivity in COS compared with controls. Here, we ask whether COS and AOS patients and their siblings exhibit similar abnormalities of functional connectivity. Methods:...
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Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping, based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI....
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Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI....
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Objective: Working memory (WM) deficits are consistently reported in schizophrenia and are related to poor functional outcomes. Functional magnetic resonance imaging studies of adult-onset schizophrenia have reported decreased functional activations and connectivity in the WM network, but no prior functional magnetic resonance imaging study has ex...
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Objective: This study investigated symptom dimensions and subgroups in the National Institute of Mental Health (NIMH) childhood-onset schizophrenia (COS) cohort and their similarities to adult-onset schizophrenia (AOS) literature. Method: Scores from the Scales for the Assessment of Positive and Negative Symptoms (SAPS & SANS) from 125 COS patie...
Preprint
Full-text available
Evolutionary and developmental increases in primate brain size have been accompanied by systematic shifts in the proportionality of different primate brain systems. However, it remains unknown if and how brain patterning varies across the more than 2-fold inter-individual variation in brain size that occurs amongst typically-developing humans. Usin...
Preprint
A critical issue in many neuroimaging studies is the comparison between brain maps. How should we test the hypothesis that two or more brain maps are partially convergent or overlap to a significant extent? This “correspondence problem” affects, for example, the interpretation of comparisons between task-based patterns of functional activation, res...
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Full-text available
Objective Gender differences, including younger age of onset and greater premorbid deficits in men, have been reported in adult-onset schizophrenia. This study comprehensively evaluated gender differences in childhood-onset schizophrenia (COS), a rare variant of the disorder. Method Demographic, premorbid, clinical, familial, and cognitive charact...
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To demonstrate that the temporal signal-to-noise ratio (SNR) of generalized autocalibrating partially parallel acquisitions (GRAPPA) accelerated echo planar imaging (EPI) can be enhanced and made more spatially uniform by using a fast low angle shot (FLASH) based calibration scan. EPI of a phantom and human brains were acquired at 3 Tesla without a...
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Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a c...
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Past experience of everyday life activities, which forms the basis of our knowledge about the world, greatly affects how we understand stories. Yet, little is known about how this influence is instantiated in the human brain. Here, we used functional magnetic resonance imaging to investigate how past experience facilitates functional connectivity d...
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The neural correlates of narrative production and comprehension remain poorly understood. Here, using PET, fMRI, contrast and functional network connectivity analyses we comprehensively characterize the neural mechanisms underlying these complex behaviors. Eighteen healthy subjects told and listened to fictional stories during scanning. In addition...
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Background: Three aspects of language production are impaired to different degrees in individuals with post-stroke aphasia: ability to repeat words and nonwords, name pictures, and produce sentences. These impairments often persist into the chronic stages, and the neuroanatomical distribution of lesions associated with chronicity of each of these i...
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The embodied view of language processing proposes that comprehension involves multimodal simulations, a process that retrieves a comprehender's perceptual, motor, and affective knowledge through reactivation of the neural systems responsible for perception, action, and emotion. Although evidence in support of this idea is growing, the contemporary...
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The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvis...
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Measurement of individual organ tissue oxygen levels can provide information to help evaluate and optimize medical interventions in many areas including wound healing, resuscitation strategies, and cancer therapeutics. Echo planar (19) F MRI has previously focused on tumor oxygen measurement at low oxygen levels (pO(2)) <30 mmHg. It uses the linear...
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Human embryonic stem cells (hESC) can generate cardiomyocytes (CM), which offer promising treatments for cardiomyopathies in children. However, challenges for clinical translation result from loss of transplanted cell from target sites and high cell death. An imaging technique that noninvasively and repetitively monitors transplanted hESC-CM could...
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Acute myocardial infarction (MI) involves necrotic and apoptotic loss of cardiomyocytes. One strategy to salvage ischemic cardiomyocytes is to modulate gene expression to promote cell survival without disturbing normal cardiac function. MicroRNAs (miRNAs) have emerged as powerful regulators of multiple cellular processes, including apoptosis, sugge...
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Natural killer (NK) cells are lymphocytes of the innate immune system that are critical for the host defense against viruses and cancer through their rapid and direct cytotoxic activity against infected and malignant cells. The antitumor activity of NK cells has been extensively investigated with respect to mechanisms of immunosurveillance, escape...
Conference Paper
PURPOSE To optimize a labeling protocol for human embryonic stem cell derived cardiomyocytes (hESC-CMs) with FDA-approved Ferumoxides for tracking with MR imaging. METHOD AND MATERIALS hESCs were labeled with Ferumoxides (50 μg Fe/ml) by simple incubation for 24 hr either (I) before differentiation into beating CMs or (II) after CM differentiation...
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To compare magnetic resonance (MR) signal characteristics of contrast agent-labeled apoptotic and viable human mesenchymal stem cells (hMSCs) in matrix-associated stem cell implants. hMSCs were labeled with Food and Drug Administration-approved ferumoxides nanoparticles. One group (A) remained untreated whereas a second group (B) underwent mitomyci...
Conference Paper
Multimodality imaging is increasingly relevant in many clinical and preclinical fields. PET/CT and SPECT/CT studies, for instance, generally provide more information than the same imaging modalities taken separately. This synergistic effect, obtained by combining anatomical and functional information, also would be desirable for magnetic resonance...