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1.
Proc Natl Acad Sci U S A ; 120(21): e2218478120, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37192167

ABSTRACT

Aneuploidy syndromes impact multiple organ systems but understanding of tissue-specific aneuploidy effects remains limited-especially for the comparison between peripheral tissues and relatively inaccessible tissues like brain. Here, we address this gap in knowledge by studying the transcriptomic effects of chromosome X, Y, and 21 aneuploidies in lymphoblastoid cell lines, fibroblasts and iPSC-derived neuronal cells (LCLs, FCL, and iNs, respectively). We root our analyses in sex chromosome aneuploidies, which offer a uniquely wide karyotype range for dosage effect analysis. We first harness a large LCL RNA-seq dataset from 197 individuals with one of 6 sex chromosome dosages (SCDs: XX, XXX, XY, XXY, XYY, and XXYY) to i) validate theoretical models of SCD sensitivity and ii) define an expanded set of 41 genes that show obligate dosage sensitivity to SCD and are all in cis (i.e., reside on the X or Y chromosome). We then use multiple complementary analyses to show that cis effects of SCD in LCLs are preserved in both FCLs (n = 32) and iNs (n = 24), whereas trans effects (i.e., those on autosomal gene expression) are mostly not preserved. Analysis of additional datasets confirms that the greater cross-cell type reproducibility of cis vs. trans effects is also seen in trisomy 21 cell lines. These findings i) expand our understanding of X, Y, and 21 chromosome dosage effects on human gene expression and ii) suggest that LCLs may provide a good model system for understanding cis effects of aneuploidy in harder-to-access cell types.


Subject(s)
Aneuploidy , Down Syndrome , Humans , Reproducibility of Results , Down Syndrome/genetics , Sex Chromosomes , Gene Expression
2.
J Neurosci ; 43(8): 1321-1333, 2023 02 22.
Article in English | MEDLINE | ID: mdl-36631267

ABSTRACT

All eutherian mammals show chromosomal sex determination with contrasting sex chromosome dosages (SCDs) between males (XY) and females (XX). Studies in transgenic mice and humans with sex chromosome trisomy (SCT) have revealed direct SCD effects on regional mammalian brain anatomy, but we lack a formal test for cross-species conservation of these effects. Here, we develop a harmonized framework for comparative structural neuroimaging and apply this to systematically profile SCD effects on regional brain anatomy in both humans and mice by contrasting groups with SCT (XXY and XYY) versus XY controls. Total brain size was substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Robust and spatially convergent effects of XXY and XYY on regional brain volume were observed in humans, but not mice, when controlling for global volume differences. However, mice do show subtle effects of XXY and XYY on regional volume, although there is not a general spatial convergence in these effects within mice or between species. Notwithstanding this general lack of conservation in SCT effects, we detect several brain regions that show overlapping effects of XXY and XYY both within and between species (cerebellar, parietal, and orbitofrontal cortex), thereby nominating high priority targets for future translational dissection of SCD effects on the mammalian brain. Our study introduces a generalizable framework for comparative neuroimaging in humans and mice and applies this to achieve a cross-species comparison of SCD effects on the mammalian brain through the lens of SCT.SIGNIFICANCE STATEMENT Sex chromosome dosage (SCD) affects neuroanatomy and risk for psychopathology in humans. Performing mechanistic studies in the human brain is challenging but possible in mouse models. Here, we develop a framework for cross-species neuroimaging analysis and use this to show that an added X- or Y-chromosome significantly alters human brain anatomy but has muted effects in the mouse brain. However, we do find evidence for conserved cross-species impact of an added chromosome in the fronto-parietal cortices and cerebellum, which point to regions for future mechanistic dissection of sex chromosome dosage effects on brain development.


Subject(s)
Brain , Sex Chromosomes , Male , Female , Humans , Mice , Animals , Brain/anatomy & histology , Neuroimaging , Cerebellum , Mice, Transgenic , Mammals
3.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Article in English | MEDLINE | ID: mdl-33811142

ABSTRACT

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 longitudinal data, analysis of whole-brain average anatomical imbalance reveals a reproducible tightening of structural covariance by age 25 y, which loosens after the seventh decade of life. Anatomical imbalance change in development and in aging is greatest in the association cortex and least in the sensorimotor cortex. Finally, we show that interindividual variation in whole-brain average anatomical imbalance is positively correlated with a marker of human prenatal stress (birthweight disparity between monozygotic twins) and negatively correlated with general cognitive ability. This work provides methods and empirical insights to advance our understanding of coordinated anatomical organization of the human brain and its interindividual variation.


Subject(s)
Cerebral Cortex/growth & development , Magnetic Resonance Imaging/methods , Adolescent , Adult , Biological Variation, Population , Cerebral Cortex/diagnostic imaging , Connectome , Female , Humans , Male
4.
Cereb Cortex ; 31(12): 5339-5353, 2021 10 22.
Article in English | MEDLINE | ID: mdl-34117759

ABSTRACT

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 knowledge of how these changes might relate to known alterations in gray matter anatomy. Thus, here, we use voxel-based morphometry on structural neuroimaging data to provide the first comprehensive maps of regional white matter volume (WMV) changes across individuals with varying SCD (n = 306). We show that mounting X- and Y-chromosome dosage are both associated with widespread WMV decreases, including in cortical, subcortical, and cerebellar tracts, as well as WMV increases in the genu of the corpus callosum and posterior thalamic radiation. We also correlate X- and Y-chromosome-linked WMV changes in certain regions to measures of internalizing and externalizing psychopathology. Finally, we demonstrate that SCD-driven WMV changes show a coordinated coupling with SCD-driven gray matter volume changes. These findings represent the most complete maps of X- and Y-chromosome effects on human white matter to date, and show how such changes connect to psychopathological symptoms and gray matter anatomy.


Subject(s)
White Matter , Brain/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Magnetic Resonance Imaging/methods , Sex Chromosomes , White Matter/diagnostic imaging , White Matter/pathology
5.
Cereb Cortex ; 31(9): 4180-4190, 2021 07 29.
Article in English | MEDLINE | ID: mdl-34009243

ABSTRACT

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 magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males to 1) implement a brain-wide screen for altered global resting-state functional connectivity (rsFC) in XXY versus XY males and 2) decompose these alterations through seed-based analysis. We then compared these rsFC findings with measures of regional brain anatomy, psychopathology, and cognition. XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC)-reflecting DLPFC overconnectivity with diverse rsFC networks. Functional overconnectivity was partly coupled to co-occurring regional volumetric changes in XXY syndrome, and variation in DLPFC-precuneus rsFC was correlated with the severity of psychopathology. By providing the first view of altered rsFC in XXY syndrome and contextualizing observed changes relative to neuroanatomy and behavior, our study helps to advance biological understanding of XXY syndrome-both as a disorder in its own right and more broadly as a model of genetic risk for psychopathology.


Subject(s)
Chromosomes, Human, X/genetics , Klinefelter Syndrome/genetics , Klinefelter Syndrome/psychology , Neural Pathways/physiology , Adolescent , Child , Chromosomes, Human, Y/genetics , Female , Humans , Intelligence Tests , Klinefelter Syndrome/diagnostic imaging , Magnetic Resonance Imaging , Male , Mental Disorders/genetics , Mental Disorders/psychology , Neural Pathways/diagnostic imaging , Neuroimaging , Parietal Lobe/diagnostic imaging , Parietal Lobe/physiopathology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Young Adult
6.
AJR Am J Roentgenol ; 217(1): 172-176, 2021 07.
Article in English | MEDLINE | ID: mdl-33909466

ABSTRACT

OBJECTIVE. In children (4 months to 8 years old), radiographic measurements of the acetabular index are the preferred method to assess developmental hip dysplasia. However, the acetabular index has been criticized as having variable reliability owing to difficulty identifying the correct anatomic landmarks. An alternative method of measuring the acetabular index using the ischium is being proposed to avoid the variability of the triradiate cartilage line as a reference point. With the alternative method, the acetabular index is derived by measuring the angle between a line connecting the ischial tuberosi-ties and a line connecting the inferomedial and superolateral edges of the acetabulum. The purpose of this study was to evaluate the accuracy and reliability of this alternative method of measuring the acetabular index compared with the traditional method. MATERIALS AND METHODS. Children 4 months to 8 years old who presented for evaluation of developmental dysplasia of the hip were included. Two physicians, each using both the traditional and the alternative method, measured acetabular indexes on all radiographs. Accuracy was defined as mean absolute error less than 6°. Reliability was calculated by means of intraclass correlation coefficient (ICC). RESULTS. Pelvic radiographs of 40 children (324 hips) were included. The mean age was 23.7 months (range, 4-96 months) and mean acetabular index was 24.2° (range, 8-50°). The alternative method was associated with mean absolute error of 2.50°, which is significantly below the threshold of 6° (t < 0.001). Intrarater reliability for the traditional method was high (ICC, 0.81) and for the alternative method was very high (ICC, 0.92). Interrater reliability for the traditional method was high (ICC, 0.89) and for the alternative method was very high (ICC, 0.91). CONCLUSION. Measuring the acetabular index using the alternative method has very high accuracy and intrarater and interrater reliability.


Subject(s)
Acetabulum/anatomy & histology , Body Weights and Measures/methods , Hip Dislocation, Congenital/diagnostic imaging , Radiography/methods , Acetabulum/diagnostic imaging , Child , Child, Preschool , Female , Humans , Infant , Male , Reproducibility of Results
7.
J Neurosci ; 39(8): 1365-1373, 2019 02 20.
Article in English | MEDLINE | ID: mdl-30587541

ABSTRACT

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 morphology between ages 5 and 25 years. We found positive associations between SES and total volumes of the brain, cortical sheet, and four separate subcortical structures. These associations were stable between ages 5 and 25. Surface-based shape analysis revealed that higher SES is associated with areal expansion of lateral prefrontal, anterior cingulate, lateral temporal, and superior parietal cortices and ventrolateral thalamic, and medial amygdalo-hippocampal subregions. Meta-analyses of functional imaging data indicate that cortical correlates of SES are centered on brain systems subserving sensorimotor functions, language, memory, and emotional processing. We further show that anatomical variation within a subset of these cortical regions partially mediates the positive association between SES and IQ. Finally, we identify neuroanatomical correlates of SES that exist above and beyond accompanying variation in IQ. Although SES is clearly a complex construct that likely relates to development through diverse, nondeterministic processes, our findings elucidate potential neuroanatomical mediators of the association between SES and cognitive outcomes.SIGNIFICANCE STATEMENT Childhood socioeconomic status (SES) has been associated with developmental disparities in mental health, cognitive ability, and academic achievement, but efforts to understand underlying SES-brain relationships are ongoing. Here, we leverage a unique developmental neuroimaging dataset to longitudinally map the associations between SES and regional brain anatomy at high spatiotemporal resolution. We find widespread associations between SES and global cortical and subcortical volumes and surface area and localize these correlations to a distributed set of cortical, thalamic, and amygdalo-hippocampal subregions. Anatomical variation within a subset of these regions partially mediates the positive relationship between SES and IQ. Our findings help to localize cortical and subcortical systems that represent candidate biological substrates for the known relationships between SES and cognition.


Subject(s)
Brain/anatomy & histology , Cognition/physiology , Social Class , Social Determinants of Health , Adolescent , Adult , Adverse Childhood Experiences , Brain/growth & development , Cerebral Cortex/anatomy & histology , Cerebral Cortex/growth & development , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Intelligence Tests , Longitudinal Studies , Magnetic Resonance Imaging , Male , Neuroimaging , Organ Size , Reference Values , Young Adult
8.
Neuroimage ; 204: 116122, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31470127

ABSTRACT

The amygdala and hippocampus are two adjacent allocortical structures implicated in sex-biased and developmentally-emergent psychopathology. However, the spatiotemporal dynamics of amygdalo-hippocampal development remain poorly understood in healthy humans. The current study defined trajectories of volume and shape change for the amygdala and hippocampus by applying a multi-atlas segmentation pipeline (MAGeT-Brain) and semi-parametric mixed-effects spline modeling to 1,529 longitudinally-acquired structural MRI brain scans from a large, single-center cohort of 792 youth (403 males, 389 females) between the ages of 5 and 25 years old. We found that amygdala and hippocampus volumes both follow curvilinear and sexually dimorphic growth trajectories. These sex-biases were particularly striking in the amygdala: males showed a significantly later and slower adolescent deceleration in volume expansion (at age 20 years) than females (age 13 years). Shape analysis localized significant hot-spots of sex-biased anatomical development in sub-regional territories overlying rostral and caudal extremes of the CA1/2 in the hippocampus, and the centromedial nuclear group of the amygdala. In both sexes, principal components analysis revealed close integration of amygdala and hippocampus shape change along two main topographically-organized axes - low vs. high areal expansion, and early vs. late growth deceleration. These results (i) bring greater resolution to our spatiotemporal understanding of amygdalo-hippocampal development in healthy males and females, and (ii) uncover focal sex-differences in the structural maturation of the brain components that may contribute to differences in behavior and psychopathology that emerge during adolescence.


Subject(s)
Amygdala , Hippocampus , Human Development/physiology , Neuroimaging/methods , Sex Characteristics , Adolescent , Adult , Amygdala/anatomy & histology , Amygdala/diagnostic imaging , Amygdala/growth & development , Atlases as Topic , Child , Child, Preschool , Female , Hippocampus/anatomy & histology , Hippocampus/diagnostic imaging , Hippocampus/growth & development , Humans , Longitudinal Studies , Male , Young Adult
9.
Am J Med Genet C Semin Med Genet ; 184(2): 493-505, 2020 06.
Article in English | MEDLINE | ID: mdl-32515138

ABSTRACT

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 cognitive ability (estimated using full-scale IQ [FSIQ] from Wechsler scales) and regional estimates of SA and CT (from structural MRI scans) in both aneuploid (28 XXX, 55 XXY, 22 XYY, 19 XXYY) and typically-developing euploid (79 XX, 85 XY) individuals. Results indicated widespread decoupling of normative anatomical-cognitive relationships in SCA: we found five regions where SCA significantly altered SA-FSIQ relationships, and five regions where SCA significantly altered CT-FSIQ relationships. The majority of areas were characterized by the presence of positive anatomy-IQ relationships in health, but no or slightly negative anatomy-IQ relationships in SCA. Disrupted anatomical-cognitive relationships generalized from the full cohort to karyotypically defined subcohorts (i.e., XX-XXX; XY-XYY; XY-XXY), demonstrating continuity across multiple supernumerary SCA conditions. As the first direct evidence of altered regional neuroanatomical-cognitive relationships in supernumerary SCA, our findings shed light on potential genetic and structural correlates of the cognitive phenotype in SCA, and may have implications for other neurogenetic disorders.


Subject(s)
Brain/physiopathology , Cognition/physiology , Sex Chromosome Aberrations , Sex Chromosomes/genetics , Aneuploidy , Brain/diagnostic imaging , Brain Cortical Thickness , Cohort Studies , Female , Humans , Karyotyping , Magnetic Resonance Imaging , Male , Neuroanatomy/methods , Sex Chromosomes/physiology
10.
Brain ; 139(Pt 1): 276-91, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26493637

ABSTRACT

Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia.


Subject(s)
Brain/physiopathology , Cognition , Schizophrenia, Childhood/physiopathology , Schizophrenia, Childhood/psychology , Social Behavior , Adolescent , Case-Control Studies , Echo-Planar Imaging , Female , Functional Neuroimaging , Humans , Male , Neural Pathways/physiopathology , Schizophrenia, Childhood/diagnosis , Young Adult
11.
Cereb Cortex ; 26(7): 2982-90, 2016 07.
Article in English | MEDLINE | ID: mdl-26088974

ABSTRACT

Detailed descriptions of cortical anatomy in youth with Down syndrome (DS), the most common genetic cause of intellectual disability (ID), are scant. Thus, the current study examined deviations in cortical thickness (CT) and surface area (SA), at high spatial resolution, in youth with DS, to identify focal differences relative to typically developing (TD) youth. Participants included 31 youth with DS and 45 age- and sex-matched TD controls (mean age ∼16 years; range = 5-24 years). All participants completed T1-weighted ASSET-calibrated magnetization prepared rapid gradient echo scans on a 3-T magnetic resonance imaging scanner. Replicating prior investigations, cortical volume was reduced in DS compared with controls. However, a novel dissociation for SA and CT was found-namely, SA was reduced (predominantly in frontal and temporal regions) while CT was increased (notably in several regions thought to belong to the default mode network; DMN). These findings suggest that reductions in SA rather than CT are driving the cortical volume reductions reported in prior investigations of DS. Moreover, given the link between DMN functionality and Alzheimer's symptomatology in chromosomally typical populations, future DS studies may benefit from focusing on the cortex in DMN regions, as such investigations may provide clues to the precocious onset of Alzheimer's disease in this at-risk group.


Subject(s)
Cerebral Cortex/diagnostic imaging , Down Syndrome/diagnostic imaging , Adolescent , Alzheimer Disease/diagnostic imaging , Analysis of Variance , Cerebral Cortex/growth & development , Child , Child, Preschool , Female , Humans , Intelligence , Intelligence Tests , Magnetic Resonance Imaging , Male , Organ Size , Young Adult
12.
J Neurosci ; 35(1): 140-5, 2015 Jan 07.
Article in English | MEDLINE | ID: mdl-25568109

ABSTRACT

The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.


Subject(s)
Aneuploidy , Brain Mapping/methods , Brain/abnormalities , Brain/physiology , Sex Chromosomes/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Longitudinal Studies , Male , Young Adult
13.
Hum Brain Mapp ; 37(7): 2385-97, 2016 07.
Article in English | MEDLINE | ID: mdl-27004471

ABSTRACT

While the potential for small amounts of motion in functional magnetic resonance imaging (fMRI) scans to bias the results of functional neuroimaging studies is well appreciated, the impact of in-scanner motion on morphological analysis of structural MRI is relatively under-studied. Even among "good quality" structural scans, there may be systematic effects of motion on measures of brain morphometry. In the present study, the subjects' tendency to move during fMRI scans, acquired in the same scanning sessions as their structural scans, yielded a reliable, continuous estimate of in-scanner motion. Using this approach within a sample of 127 children, adolescents, and young adults, significant relationships were found between this measure and estimates of cortical gray matter volume and mean curvature, as well as trend-level relationships with cortical thickness. Specifically, cortical volume and thickness decreased with greater motion, and mean curvature increased. These effects of subtle motion were anatomically heterogeneous, were present across different automated imaging pipelines, showed convergent validity with effects of frank motion assessed in a separate sample of 274 scans, and could be demonstrated in both pediatric and adult populations. Thus, using different motion assays in two large non-overlapping sets of structural MRI scans, convergent evidence showed that in-scanner motion-even at levels which do not manifest in visible motion artifact-can lead to systematic and regionally specific biases in anatomical estimation. These findings have special relevance to structural neuroimaging in developmental and clinical datasets, and inform ongoing efforts to optimize neuroanatomical analysis of existing and future structural MRI datasets in non-sedated humans. Hum Brain Mapp 37:2385-2397, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Motion , Pattern Recognition, Automated , Adolescent , Adult , Artifacts , Brain/growth & development , Child , Child, Preschool , Female , Gray Matter/diagnostic imaging , Gray Matter/growth & development , Humans , Male , Organ Size , Young Adult
15.
J Strength Cond Res ; 29(1): 80-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25068802

ABSTRACT

Remote ischemic preconditioning (RIPC) provides a substantial benefit for heart protection during surgery. Recent literature on RIPC reveals the potential to benefit the enhancement of sports performance as well. The aim of this study was to investigate the effect of RIPC on anaerobic performance. Seventeen healthy participants who practice regular physical activity participated in the project (9 women and 8 men, mean age 28 ± 8 years). The participants were randomly assigned to an RIPC intervention (four 5-minute cycles of ischemia reperfusion, followed by 5 minutes using a pressure cuff) or a SHAM intervention in a crossover design. After the intervention, the participants were tested for alactic anaerobic performance (6 seconds of effort) followed by a Wingate test (lactic system) on an electromagnetic cycle ergometer. The following parameters were evaluated: average power, peak power, the scale of perceived exertion, fatigue index (in watt per second), peak power (in Watt), time to reach peak power (in seconds), minimum power (in Watt), the average power-to-weight ratio (in watt per kilogram), and the maximum power-to-weight ratio (in watt per kilogram). The peak power for the Wingate test is 794 W for RIPC and 777 W for the control group (p = 0.208). The average power is 529 W (RIPC) vs. 520 W for controls (p = 0.079). Perceived effort for RIPC is 9/10 on the Borg scale vs. 10/10 for the control group (p = 0.123). Remote ischemic preconditioning does not offer any significant benefits for anaerobic performance.


Subject(s)
Anaerobic Threshold/physiology , Arm/blood supply , Athletic Performance/physiology , Ischemic Preconditioning/methods , Adult , Cross-Over Studies , Exercise Test , Fatigue , Female , Humans , Male , Physical Exertion
16.
Cereb Cortex ; 23(1): 127-38, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22275481

ABSTRACT

The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive "pruning" of short-distance functional connections in schizophrenia.


Subject(s)
Brain Mapping/methods , Brain/physiopathology , Connectome/methods , Nerve Net/physiopathology , Neural Pathways/physiopathology , Schizophrenia/physiopathology , Adolescent , Brain/pathology , Humans , Male , Nerve Net/pathology , Neural Pathways/pathology , Prognosis , Reference Values , Reproducibility of Results , Schizophrenia/pathology , Sensitivity and Specificity , Statistics as Topic , Young Adult
17.
J Pediatr Orthop ; 34(4): 411-4, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24248590

ABSTRACT

BACKGROUND: Various pediatric conditions often necessitate a morphologic examination of the hip joint in infancy or childhood, and multiple imaging options have been employed to achieve this goal. Arthrography is one such modality. Different types of contrast media have been utilized and include pharmacologic contrast agents, air, and carbon dioxide. There are scattered reports of complications related to the typical various media used during arthrography. Some of the most concerning are related to gas emboli following the use of air or carbon dioxide. This study assesses the potential complications of carbon dioxide hip arthrography in a series of children over a 12-year period. METHODS: A retrospective review of the medical records of children between the ages of 0 and 3 years who underwent hip arthrography using carbon dioxide gas as the contrast medium was conducted. Outcome measures analyzed included volume of CO2 injected, vital signs, and perioperative and postoperative end-tidal CO2. RESULTS: Our study population was comprised of 118 hips in 90 children. We found no correlation between the volume of CO2 injected and the patient's vital signs or end-tidal CO2 at any point during the perioperative or postoperative period. None of the children exhibited any evidence for cardiopulmonary compromise or clinical signs of embolism. DISCUSSION: To our knowledge, there have been no large studies reporting on carbon dioxide arthrography and its potential complications. There were no gas embolisms and/or cardiopulmonary complications in our patients in the perioperative, postoperative, or 1-year follow-up period. Utilizing carbon dioxide gas as the contrast media for hip arthrography in children is safe and can help aid in the treatment of pediatric hip conditions. LEVEL OF EVIDENCE: Therapeutic Level IV.


Subject(s)
Arthrography/methods , Carbon Dioxide , Hip Dislocation, Congenital/diagnostic imaging , Hip Joint/diagnostic imaging , Arthrography/adverse effects , Arthrography/standards , Carbon Dioxide/adverse effects , Child, Preschool , Contrast Media , Embolism, Air/etiology , Female , Follow-Up Studies , Hip Dislocation, Congenital/surgery , Humans , Infant , Infant, Newborn , Intraoperative Complications/etiology , Male , Postoperative Complications/etiology , Postoperative Period , Reproducibility of Results , Retrospective Studies
18.
Biol Psychiatry ; 95(2): 136-146, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37480975

ABSTRACT

BACKGROUND: Diverse gene dosage disorders (GDDs) increase risk for psychiatric impairment, but characterization of GDD effects on the human brain has so far been piecemeal, with few simultaneous analyses of multiple brain features across different GDDs. METHODS: Here, through multimodal neuroimaging of 3 aneuploidy syndromes (XXY [total n = 191, 92 control participants], XYY [total n = 81, 47 control participants], and trisomy 21 [total n = 69, 41 control participants]), we systematically mapped the effects of supernumerary X, Y, and chromosome 21 dosage across a breadth of 15 different macrostructural, microstructural, and functional imaging-derived phenotypes (IDPs). RESULTS: The results revealed considerable diversity in cortical changes across GDDs and IDPs. This variegation of IDP change underlines the limitations of studying GDD effects unimodally. Integration across all IDP change maps revealed highly distinct architectures of cortical change in each GDD along with partial coalescence onto a common spatial axis of cortical vulnerability that is evident in all 3 GDDs. This common axis shows strong alignment with shared cortical changes in behaviorally defined psychiatric disorders and is enriched for specific molecular and cellular signatures. CONCLUSIONS: Use of multimodal neuroimaging data in 3 aneuploidies indicates that different GDDs impose unique fingerprints of change in the human brain that differ widely depending on the imaging modality that is being considered. Embedded in this variegation is a spatial axis of shared multimodal change that aligns with shared brain changes across psychiatric disorders and therefore represents a major high-priority target for future translational research in neuroscience.


Subject(s)
Brain , Mental Disorders , Humans , Brain/diagnostic imaging , Aneuploidy , Neuroimaging
19.
Mil Med ; 188(5-6): e942-e948, 2023 05 16.
Article in English | MEDLINE | ID: mdl-34652444

ABSTRACT

INTRODUCTION: Members of the Canadian Armed Forces (CAF) are required to meet the minimum standards of the Fitness for Operational Requirements of CAF Employment (FORCE) job-based simulation test (JBST) and must possess the capacity to perform other common essential tasks. One of those tasks is to perform basic fire management tasks during fire emergencies to mitigate damage and reduce the risk of injuries and/or death until professional firefighters arrive at the scene. To date however, the physiological demands of common firefighting tasks have mostly been performed on professional firefighters, thus rendering the transferability of the demands to the general military population unclear. This pilot study aimed to quantify, for the first time, the physiological demands of basic fire management tasks in the military, to determine if they are reflected in the FORCE JBST minimum standard. We hypothesized that the physiological demands of basic fire management tasks within the CAF are below the physiological demands of the FORCE JBST minimum standard, and as such, be lower than the demands of professional firefighting. MATERIALS AND METHODS: To achieve this, 21 CAF members (8 females; 13 males; mean [SD] age: 33 [10] years; height: 174.5 [10.5] cm; weight: 85.4 [22.1] kg, estimated maximal oxygen uptake [$\dot V$O2peak]: 44.4 (7.4) mL kg-1 min-1) participated in a realistic, but physically demanding, JBST developed by CAF professional firefighting subject matter experts. The actions included lifting, carrying, and manipulating a 13-kg powder fire extinguisher and connecting, coupling, and dragging a 38-mm fire hose over 30 m. The rate of oxygen uptake ($\dot V$O2), heart rate, and percentage of heart rate reserve were measured continuously during two task simulation trials, which were interspersed by a recovery period. Rating of perceived exertion (6-no exertion; 20-maximal exertion) was measured upon completion of both task simulations. Peak $\dot V$O2 ($\dot V$O2peak) was estimated based on the results of the FORCE JBST. RESULTS: The mean (SD) duration of both task simulation trials was 3:39 (0:19) min:s, whereas the rest period in between both trials was 62 (19) minutes. The mean O2 was 21.1 (4.7) mL kg-1 min-1 across trials, which represented 52.1 (12.2) %$\dot V$O2peak and ∼81% of the FORCE JBST. This was paralleled by a mean heart rate of 136 (18) beats min-1, mean percentage of heart rate reserve of 61.2 (10.8), and mean rating of perceived exertion of 11 ± 2. Other physical components of the JBST consisted of lifting, carrying, and manipulating a 13-kg load for ∼59 seconds, which represents 65% of the load of the FORCE JBST. The external resistance of the fire hose drag portion increased up to 316 N, translating to a total of 6205 N over 30 m, which represents 96% of the drag force measured during the FORCE JBST. CONCLUSIONS: Our findings demonstrate that the physiological demands of basic fire management tasks in the CAF are of moderate intensity, which are reflected in the CAF physical fitness standard. As such, CAF members who achieve the minimum standard on the FORCE JBST are deemed capable of physically performing basic fire management tasks during fire emergencies.


Subject(s)
Military Personnel , Male , Female , Humans , Adult , Pilot Projects , Emergencies , Canada , Heart Rate/physiology , Oxygen , Physical Exertion/physiology
20.
J Sports Med Phys Fitness ; 63(2): 367-372, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35816147

ABSTRACT

BACKGROUND: Triathletes' physiological adaptations to exercise training can have a different impact on cardiac remodeling based on the extreme exercise preparation. Moreover, cardiac remodeling might be different depending on whether triathletes have trained for many years or if they just decided to be more active. Nevertheless, data are limited in amateur endurance athletes and studies about them are key for their safety. Therefore, we investigated the effects of exercise training for a half-ironman on cardiac remodeling. METHODS: A total of 24 amateur athletes underwent a 24-week exercise program and were followed by three-dimensional echocardiography to assess its global impact on cardiac remodeling. Subanalyses were performed based on participants past-training experience (low versus high). RESULTS: We found significant group effects on the right and left ventricle, significant time effect on the right ventricle. No significant interaction effects were observed. We observed significant correlations between the right ventricle, clinical and performance characteristics where the peak power output explained 38% of the variance, while the body surface area, weight and power at the second ventilatory threshold explained 34%, 31% and 30%, respectively. CONCLUSIONS: Changes in cardiac remodeling in response to an exercise program for a half-ironman are not homogeneous across the ventricles and are influenced by participants' past-training experience. This study strengthens our knowledge of extreme exercise training for a half-ironman to further develop better training programs and medical follow-up in amateur triathletes.


Subject(s)
Physical Endurance , Ventricular Remodeling , Humans , Physical Endurance/physiology , Exercise/physiology , Athletes , Heart Ventricles/diagnostic imaging
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