Browsing by Author "Long, Xiangyu"

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    Age-related functional brain changes in young children
    (Elsevier, 2017-07-15) Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine A.
    Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury.
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    Altered brain white matter connectome in children and adolescents with prenatal alcohol exposure
    (Springer, 2020-04-01) Long, Xiangyu; Little, Graham; Treit, Sarah; Beaulieu, Christian; Gong, Gaolang; Lebel, Catherine
    Diffuson tensor imaging (DTI) has demonstrated widespread alterations of brain white matter structure in children with prenatal alcohol exposure (PAE), yet it remains unclear how these alterations affect the structural brain network as a whole. The present study aimed to examine changes in the DTI-based structural connectome in children and adolescents with PAE compared to unexposed controls. Participants were 121 children and adolescents with PAE (51 females) and 119 typically-developing controls (49 females) aged 5-18 years with DTI data collected at one of four research centers across Canada. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers via deterministic tractography. The PAE group had significantly decreased whole-brain global efficiency, degree centrality, and participation coefficients, as well as increased shortest path length and betweenness centrality compared to unexposed controls. Individuals with PAE had decreased connectivity between the attention, somatomotor, and default mode networks compared to controls. This study demonstrates decreased structural white matter connectivity in children and adolescents with PAE at a whole-brain level, suggesting widespread alterations in how networks are connected with each other. This decreased connectivity may underlie cognitive and behavioural difficulties in children with PAE.
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    Brain connectomes in youth at risk for serious mental illness: an exploratory analysis
    (2022-09-15) Metzak, Paul D.; Shakeel, Mohammed K.; Long, Xiangyu; Lasby, Mike; Souza, Roberto; Bray, Signe; Goldstein, Benjamin I.; MacQueen, Glenda; Wang, JianLi; Kennedy, Sidney H.; Addington, Jean; Lebel, Catherine
    Abstract Background Identifying early biomarkers of serious mental illness (SMI)—such as changes in brain structure and function—can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI. Methods Participants were classified as healthy controls (HC; n = 33), familial risk for serious mental illness (stage 0; n = 31), mild symptoms (stage 1a; n = 37), attenuated syndromes (stage 1b; n = 61), or discrete disorder (transition; n = 9) based on clinical assessments. Imaging data was collected from two sites. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers derived from constrained spherical deconvolution of the diffusion tensor imaging (DTI) scans, and from the correlations between brain regions measured with resting state functional magnetic resonance imaging (fMRI) data. Results Linear mixed effects analysis and analysis of covariance revealed no significant differences between groups in global or nodal metrics after correction for multiple comparisons. A follow up machine learning analysis broadly supported the findings. Several non-overlapping frontal and temporal network differences were identified in the structural and functional connectomes before corrections. Conclusions Results suggest significant brain connectome changes in youth at transdiagnostic risk may not be evident before illness onset.
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    The brain's functional connectome in young children with prenatal alcohol exposure
    (Elsevier, 2019-01) Long, Xiangyu; Kar, Preeti; Gibbard, Ben; Tortorelli, Christina; Lebel, Catherine
    Prenatal alcohol exposure (PAE) can lead to altered brain function and structure, as well as lifelong cognitive, behavioral, and mental health difficulties. Previous research has shown reduced brain network efficiency in older children and adolescents with PAE, but no imaging studies have examined brain differences in young children with PAE, at an age when cognitive and behavioral problems often first become apparent. The present study aimed to investigate the brain's functional connectome in young children with PAE using passive viewing fMRI. We analyzed 34 datasets from 26 children with PAE aged 2-7 years and 215 datasets from 87 unexposed typically-developing children in the same age range. The whole brain functional connectome was constructed using functional connectivity analysis across 90 regions for each dataset. We examined intra- and inter-participant stability of the functional connectome, graph theoretical measurements, and their correlations with age. Children with PAE had similar inter- and intra-participant stability to controls. However, children with PAE, but not controls, showed increasing intra-participant stability with age, suggesting a lack of variability of intrinsic brain activity over time. Inter-participant stability increased with age in controls but not in children with PAE, indicating more variability of brain function across the PAE population. Global graph metrics were similar between children with PAE and controls, in line with previous studies in older children. This study characterizes the functional connectome in young children with PAE for the first time, suggesting that the increased brain variability seen in older children develops early in childhood, when participants with PAE fail to show the expected age-related increases in inter-individual stability.
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    Evaluation of Brain Alterations and Behavior in Children With Low Levels of Prenatal Alcohol Exposure
    (2022-04-01) Long, Xiangyu; Lebel, Catherine
    IMPORTANCE: High levels of prenatal alcohol exposure (PAE) are associated with widespread behavioral and cognitive problems as well as structural alterations of the brain. However, it remains unclear whether low levels of PAE affect brain structure and function, and prior studies generally have not had well-matched control populations (eg, for sociodemographic variables). OBJECTIVE To compare structural brain alterations and behavioral changes in children with lower levels of PAE with those of well-matched controls with no PAE. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants were selected from the Adolescent Brain Cognitive Development study. Children with PAE were compared with controls matched for age, sex, family income, maternal educational level, and caregiver status. Neither group had prenatal exposure to other adverse substances (eg, tobacco, cannabis, illicit drugs). Data were collected from September 1, 2016, to November 15, 2018, and analyzed from October 14, 2020, to February 14, 2022. EXPOSURES: Diffusion tensor imaging, resting-state functional magnetic resonance imaging (MRI), and Child Behavior Checklist (CBCL) administration. MAIN OUTCOMES AND MEASURES: Fractional anisotropy (FA); mean, axial, and radial diffusivity from diffusion tensor imaging; brain functional signal variations from functional MRI; and several scores, including internalizing and externalizing behavior problems, from the CBCL. Spearman correlation coefficients between diffusion tensor imaging and functional MRI measures and the CBCL scores were calculated. RESULTS A total of 270 children were included in the analysis (mean [SD] age, 9.86 [0.46] years; 141 female [52.2%] and 129 male [47.8%]), consisting of 135 children with PAE (mean [SD] age, 9.85 [0.65] years; 73 female [54.1%] and 62 male [45.9%]) (mean exposure, 1 drink/wk) and 135 unexposed controls (mean [SD] age, 9.87 [0.04] years; 68 female [50.4%] and 67 male [49.6%]). Children with PAE had lower mean (SD) FA in white matter of the left postcentral (0.35 [0.05] vs 0.36 [0.04]; mean difference, −0.02 [95% CI, −0.03 to −0.01]), left inferior parietal (0.31 [0.07] vs 0.33 [0.06]; mean difference, −0.03 [95% CI, −0.04 to −0.01]), left planum temporale (0.26 [0.04] vs 0.28 [0.03]; mean difference, −0.02 [95% CI, −0.03 to −0.01]), left inferior occipital (0.30 [0.07] vs 0.32 [0.05]; mean difference, −0.03 [95% CI, −0.04 to −0.01]), and right middle occipital (0.30 [0.04] vs 0.31 [0.04]; mean difference, −0.01 [95% CI, −0.02 to −0.01]) areas compared with controls, and higher FA in the gray matter of the putamen (0.22 [0.03] vs 0.21 [0.02]; mean difference, 0.01 [95% CI, 0.005-0.02]). Externalizing behavior scores were higher (worse) in children with PAE than in controls (mean [SD], 45.2 [9.0] vs 42.8 [9.0]; mean difference, 2.39 [95% CI, 0.30-4.47]). Several of these regions had significant group-behavior interactions, such that the higher FA was associated with less problematic behaviors in controls (ρ range, −0.24 to −0.08) but no associations were present in the PAE group (ρ range, 0.02-0.16). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, children with low levels of PAE had lower FA and more behavioral problems compared with a well-matched control group. These results suggest that PAE, even in small amounts, has a measurable effect on brain structure in children.
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    Pre-reading language abilities and the brain's functional reading network in young children
    (Elsevier, 2020-08-15) Benischek, Alina; Long, Xiangyu; Rohr, Christiane S; Bray, Signe; Dewey, Deborah; Lebel, Catherine
    Early childhood is an important period for language development that lays the foundation for future reading abilities. However, little research has focused on the functional brain systems supporting pre-reading language abilities in typically developing children. Here, we investigated functional connectivity using passive viewing functional magnetic resonance imaging (fMRI) in 50 healthy children aged 2.85-5.07 years (3.84 ​± ​0.60 years, 22 female/28 male). Children completed the NEPSY-II Phonological Processing and Speeded Naming subtests and underwent fMRI while watching a movie of their choice. Functional connectivity was measured between key brain reading areas (bilateral angular gyrus, superior temporal gyrus, and inferior frontal gyrus) and the rest of the brain. Age-adjusted pre-reading scores positively correlated with functional connectivity between (1) the right angular gyrus and superior temporal gyrus, (2) the bilateral angular gyri and right pars triangularis and motor areas, (3) the left superior temporal gyrus and bilateral medial frontal gyrus and right cerebellum, (4) the left pars triangularis and middle occipital gyrus and insula, and (5) the right pars triangularis and the bilateral thalamus. Higher pre-reading scores were associated with stronger negative functional connectivity between (1) the left angular gyrus and auditory cortex, (2) the left superior temporal gyrus and occipital vision areas, (3) the right pars triangularis and medial frontal region, and (4) the right superior temporal gyrus and the posterior cingulate/precuneus. These results suggest better integration of the reading network, as well as its connections with other brain areas that support language or reading, and more dissociation between reading areas and the default mode network, in young children with better pre-reading skills. Our findings show that relationships between functional connectivity and pre-reading language skills are evident in young children even before formal reading instruction.
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    Sensorimotor network alterations in children and youth with prenatal alcohol exposure
    (John Wiley & Sons, 2018-05) Long, Xiangyu; Little, Graham; Beaulieu, Christian; Lebel, Catherine
    Children with prenatal alcohol exposure (PAE) often have impaired sensorimotor function. While altered brain structure has been noted in sensorimotor areas, the functional brain alterations remain unclear. This study aims to investigate sensorimotor brain networks in children and youth with PAE using resting-state functional magnetic resonance imaging (rs-fMRI). A parcellation-based network analysis was performed to identify brain networks related to hand/lower limb and face/upper limb function in 59 children and youth with PAE and 50 typically developing controls. Participants with PAE and controls had similar organization of the hand and face areas within the primary sensorimotor cortex, but participants with PAE had altered functional connectivity (FC) between the sensorimotor regions and the rest of the brain. The sensorimotor regions in the PAE group showed less connectivity to certain hubs of the default mode network and more connectivity to areas of the salience network. Overall, our results show that despite similar patterns of organization in the sensorimotor network, subjects with PAE have increased FC between this network and other brain areas, perhaps suggesting overcompensation. These alterations in the sensorimotor network lay the foundation for future studies to evaluate interventions and treatments to improve motor function in children with PAE.
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    Young children in different linguistic environments: A multimodal neuroimaging study of the inferior frontal gyrus
    (2018-07-11) Thieba, Camilia; Long, Xiangyu; Dewey, Deborah; Lebel, Catherine A.
    Magnetic resonance imaging (MRI) studies show that bilingual adults display structural and functional brain alterations, especially in the inferior frontal gyrus (IFG), dependent on when they learned their second language. However, it is unclear whether these differences are due to early exposure to another language, or to lifelong adaptation. We studied 22 children aged 3-5 years growing up in a multilingual environment and 22 age- and sex-matched controls exposed to an English-only environment. Resting-state functional MRI and T1-weighted MRI were used to assess functional connectivity and structure of the IFG. Children in a multilingual environment had higher functional connectivity between the left IFG and dorsal language and attention areas compared to children from a monolingual environment. Children in a multilingual environment also displayed decreased functional connectivity to temporal, anterior cingulate, and prefrontal areas. No significant group differences in IFG structure were observed. Our results suggest a more integrated functional language network, which is more segregated from other networks, in children who grow up in a multilingual environment. These findings suggest that functional alterations to the IFG due to second language learning occur early, while structural changes may not be apparent until later.