PRISM :: Browsing by Author "Lebel, Catherine"

Browsing by Author "Lebel, Catherine"

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Open Access
A Multimodal Approach to Understanding Motor Impairment in Developmental Coordination Disorder
(2020-07-13) Grohs, Melody N.; Dewey, Deborah, M.; Dukelow, Sean; Lebel, Catherine; Kirton, Adam; Graham, Susan; Hands, Beth
AbstractThe ability to learn, execute and adapt motor skills is fundamental to childhood development and promotes independence in daily living. Yet children with developmental coordination disorder (DCD), demonstrate difficulties acquiring and executing motor skills. DCD is a motor disorder that occurs in 5-6% of school-aged children. Motor impairment manifests as clumsy, slow and inaccurate motor performance adversely affecting the physical, academic and social outcomes of affected children. The pervasive negative impact of motor impairment on daily life in children with DCD, highlights the importance of early diagnosis and intervention. However, the motor deficits common among children with DCD remain unclear, making both screening and intervention difficult. There is a need for research with a priority focus on characterizing the motor deficits present in children with DCD. Evidence is growing, which suggests that poor motor performance in DCD is associated with motor control and motor learning deficits, however, findings are inconsistent across published studies. The current thesis used a three-pronged approach to investigate motor control and motor learning in children with diagnosed DCD, between the ages of 8 to 12 years: (1) two robotic behavioral tasks were employed to objectively quantify motor control abilities, (2) motor learning over five consecutive days of skill training and the potential of non-invasive brain stimulation to modulate rates of motor learning were explored, and (3) neuroimaging was used to investigate brain morphology of regions pertinent to motor control and motor learning. Spatial-temporal differences in reaching performance were observed in children with DCD, supporting the presence of motor control deficits. Preserved motor learning was also seen in the same sample of children. Non-invasive brain stimulation was unsuccessful in modulating the rate of motor learning. Finally, limited brain structural differences were observed in our DCD group compared to healthy controls. However, preliminary findings of reduced subcortical thalamic and pallidal volumes in our DCD group warrants further study, particularly given that these brain structures play critical roles in motor control and motor learning. Taken together, these findings suggest that the motor difficulties observed in children with DCD may be associated with compromised motor control systems.
Open Access
Advancing Concussion Assessment in Pediatrics (A-CAP): a prospective, concurrent cohort, longitudinal study of mild traumatic brain injury in children: protocol study
(BMJ, 2017-07-01) Yeates, Keith O.; Beauchamp, Miriam; Craig, William; Doan, Quynh; Zemek, Roger; Bjornson, Bruce H.; Gravel, Jocelyn; Mikrogianakis, Angelo; Goodyear, Bradley; Abdeen, Nishard; Beaulieu, Christian; Dehaes, Mathieu; Deschenes, Sylvain; Harris, Ashley D.; Lebel, Catherine; Lamont, Ryan; Williamson, Tyler; Barlow, Karen M.; Bernier, Francois; Brooks, Brian L.; Emery, Carolyn; Freedman, Stephen B.; Kowalski, Kristina; Mrklas, Kelly; Tomfohr-Madsen, Lianne; Schneider, Kathryn J.
Introduction Paediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI. Methods and analysis A-CAP is a prospective, longitudinal cohort study of children aged 8.00-16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses. Ethics and dissemination The ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals.
Open Access
Advancing the Study of Functional Connectome Development
(2023-08) Graff, Kirk; Bray, Signe; Goodyear, Brad; Lebel, Catherine
A better understanding of functional changes in the brain across childhood offers the potential to better support neurodevelopmental and learning challenges. However, neuroimaging tools such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are vulnerable to head motion and other artifacts, and studies have had limited reproducibility. To accomplish research goals, we need to understand the reliability and validity of data collection, processing, and analysis strategies. Neuroimaging datasets contain individually unique information, but identifiability is reduced by noise or lack of signal, suggesting it can be a measure of validity. The goal of this thesis was to use identifiability to benchmark different methodologies, and describe how identifiability associates with age across early childhood. I first compared several different fMRI preprocessing pipelines for data collected from young children. Preprocessing techniques are often controversial due to specific drawbacks and have typically been assessed with adult datasets, which have much less head motion. I found benefits to the use of global signal regression and temporal censoring, but overly strict censoring can impact identifiability, suggesting noise removed must be balanced against signal retained. I also compared several different EEG measures of functional connectivity (FC). EEG can be vulnerable to volume conduction artifacts that can be mitigated by only considering shared information with a time delay between signals. However, I found that mitigation strategies result in lower identifiability, suggesting that while removing confounding noise they also discard substantial signal of interest. Individual experiences may shape development in an individually unique way, which is supported by evidence that adults have more individually identifiable patterns of FC than children. I found that across 4 to 8 years of age, identifiability increased via increased self-stability, but without changes in similarity-to-others. In the absence of ground truth, it is difficult to argue for or against analysis decisions based solely on a theoretical framework and need to also be validated. My work highlights the importance of not thinking about techniques in a valid-invalid dichotomy; certain methods may be sub-optimal while still being preferable to alternatives if they better manage the trade off between noise removed and signal retained.
Open Access
Alteration in, and recovery of, cerebral activation during a working memory task following pediatric mild traumatic brain injury
(2018-01-12) Khetani, Aneesh; Barlow, Karen; Bray, Signe; Yeates, Keith; Lebel, Catherine
Introduction: Mild traumatic brain injuries (mTBIs) are most common in children and adolescents. For some, symptoms can persist for an extended duration, especially in the cognitive and working memory domains. The neurological changes that underlie these differences in children with persistent symptoms, and their recovery over time, have not been characterized at distinct time points. Objectives: To determine how cortical activation during a working memory task is different in children with persistent symptoms, relative to control and asymptomatic children, and to observe how that changes with time. Methods: This was a prospective, controlled cohort study of pediatric mTBI at approximately one- and two- months post-injury. Symptom status was determined by the post-concussion symptom inventory (PCSI). A visuospatial n-back working memory task was designed for use with functional magnetic resonance imaging (fMRI). The primary outcome measures were the blood oxygen level dependent (BOLD) signal and n-back working memory task performance. Results: 107 participants (60 symptomatic mTBI, 30 asymptomatic mTBI and 17 controls) were compared approximately one month following mTBI. Mean age was 14.2 years (SD 2.5) and 44% were male. During the n-back task, at approximately one month post-injury, symptomatic mTBI children had decreased activation in the posterior cingulate and precuneus regions compared to asymptomatic children, with no difference in performance. By approximately two months post-injury, we found that symptomatic children had less working memory related cortical activation compared to their own one month post-injury scan, and an improvement in task performance (n=45). Conclusions: Symptomatic mTBI children have cortical activation differences compared to asymptomatic children. Over time, there is a decrease in working memory functional activation within that symptomatic group. Our findings highlight the neurobiological consequences of pediatric mTBI on working memory cortical activation and recovery.
Open Access
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.
Open Access
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.
Open Access
Brain Development During Childhood and Adolescence
(2016-01-15) Mah, Alyssa; Lebel, Catherine; Frayne, Richard; Wei, Xing-Chang; Forkert, Nils; Dyck, Richard
Brain development is a combination of complex physiological changes, and various magnetic resonance imaging (MRI) techniques can help explain observed changes during development in vivo. Building upon observations from post-mortem studies, advancements in imaging and modelling techniques provide new means to further interpret the understanding of healthy brain development during childhood and adolescence. It is, however, a challenge to capture specific physiological changes, such as myelination, using MRI. This thesis uses MRI techniques – neurite orientation dispersion and density imaging (NODDI), inhomogenous magnetization transfer (ihMT), and multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) – that further characterize development in white and subcortical grey matter regions in the brain by improving specificity of the MRI signal compared to conventional techniques. Measures from NODDI, ihMT, and mcDESPOT suggest an increase in myelination and/or axonal packing during development from 0-13 years.
Open Access
Brain Structure and Mental Health Symptoms in Children and Adolescents with Prenatal Alcohol Exposure
(2023-06-12) Nakhid, Daphne Kristen Mitchell; Lebel, Catherine; McMorris, Carly; Gibbard, Ben; MacMaster, Frank
Prenatal alcohol exposure (PAE) can impact brain development, leading to an increased risk of cognitive difficulties and mental health challenges. Mental health challenges affect many people with PAE, however, associations with brain structure remain unknown. In unexposed populations, mental health symptoms are closely linked to brain volume of subcortical structures and limbic subregions. Whether there is a similar association in individuals with PAE is unknown. Beyond brain volume, iron is a key component of healthy brain development; PAE lowers fetal brain iron and may be associated with the development of mental health symptoms. Whether increased mental health symptoms in youth with PAE are associated with alterations in brain volume or brain iron of subcortical brain structures is yet to be determined. This dissertation used quantitative susceptibility mapping (QSM) and T1-weighted magnetic resonance imaging (MRI) to assess differences in brain iron and brain volume of limbic and subcortical brain regions in youth with and without PAE. Additionally, associations between brain structure and mental health symptoms were assessed within and between groups. Multiple subcortical brain structures and limbic subregions were smaller in the PAE group, but only limbic subregion volume showed associations with mental health symptoms. I found minimal group differences in magnetic susceptibility, a marker of brain iron, but many associations between brain iron and mental health symptoms within and between groups. Furthermore, PAE moderated the association between internalizing symptoms for both brain iron and subnuclei volumes in the thalamus, suggesting that the thalamus may be a unique correlate of mental health symptoms in youth with PAE. This research provides greater insight into limbic subregions that may be affected by PAE that are not observed when looking at the whole volume of a brain region. As the first study to examine magnetic susceptibility in humans with PAE, it provides important information to help understand mental health symptoms in exposed and unexposed populations. This study highlights brain structures and regions that are uniquely associated with mental health symptoms in youth with PAE. Implications of this work include increasing awareness around mental health and promoting appropriate interventions to support youth with PAE.
Open Access
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.
Open Access
Bridging the Gap - Exploring the Role of Cortisol on The Effects of Prenatal Depression on Child Neurocognition
(2022-08-19) Cattani, Danielle; Giesbrecht, Gerald; Lebel, Catherine; Campbell, Tavis
Prenatal depression is a potentially debilitating experience that can affect both birthing parent and child. The current study investigates the role of cortisol, a hormone well-known for its involvement in the stress response, in the association between prenatal depression and child neurocognitive outcomes. Specifically, we assessed child executive function and cortical thickness in the right frontal and prefrontal cortices. Pregnant participants completed the Edinburgh Postnatal Depression Scale (EPDS) to assess prenatal depression, and we examined prenatal cortisol using salivary cortisol samples. Children completed six executive function tasks spanning the three domains of executive functioning and underwent magnetic resonance imaging to assess their cortical thickness. Our results indicate that prenatal depression during pregnancy, particularly early pregnancy, has the potential to adversely impact mental flexibility in children ages 3 – 4 years. Furthermore, an elevated prenatal cortisol awakening response (CAR) was related to timing-specific and region-specific cortical thinning in the right frontal cortex of children ages 3 – 7 years. Lastly, increased CAR in the third trimester was associated with better mental flexibility outcomes. Prenatal cortisol did not mediate the relationship between prenatal depression and child cortical thickness or executive function outcomes in our sample. Future research directions are discussed. Our study emphasizes the importance of caring for prenatal mental health in improving outcomes for child neurocognition.
Open Access
Building Emotional Awareness and Mental Health (BEAM): an open-pilot and feasibility study of a digital mental health and parenting intervention for mothers of infants
(2023-02-18) Xie, E. B.; Freeman, Makayla; Penner-Goeke, Lara; Reynolds, Kristin; Lebel, Catherine; Giesbrecht, Gerald F.; Rioux, Charlie; MacKinnon, Anna; Sauer-Zavala, Shannon; Roos, Leslie E.; Tomfohr-Madsen, Lianne
Abstract Background Maternal mental health concerns and parenting stress in the first few years following childbirth are common and pose significant risks to maternal and child well-being. The COVID-19 pandemic has led to increases in maternal depression and anxiety and has presented unique parenting stressors. Although early intervention is crucial, there are significant barriers to accessing care. Methods To inform a larger randomized controlled trial, the current open-pilot trial investigated initial evidence for the feasibility, acceptability, and efficacy of a newly developed online group therapy and app-based mental health and parenting program (BEAM) for mothers of infants. Forty-six mothers 18 years or older with clinically elevated depression scores, with an infant aged 6–17 months old, and who lived in Manitoba or Alberta were enrolled in the 10-week program (starting in July 2021) and completed self-report surveys. Results The majority of participants engaged in each of the program components at least once and participants indicated relatively high levels of app satisfaction, ease of use, and usefulness. However, there was a high level of attrition (46%). Paired-sample t-tests indicated significant pre- to post-intervention change in maternal depression, anxiety, and parenting stress, and in child internalizing, but not externalizing symptoms. Effect sizes were in the medium to high range, with the largest effect size observed for depressive symptoms (Cohen’s d = .93). Discussion This study shows moderate levels of feasibility and strong preliminary efficacy of the BEAM program. Limitations to program design and delivery are being addressed for testing in adequately powered follow-up trials of the BEAM program for mothers of infants. Trial registration NCT04772677 . Registered on February 26 2021.
Open Access
Building Emotional Awareness and Mental Health (BEAM): study protocol for a phase III randomized controlled trial of the BEAM app-based program for mothers of children 18–36 months
(2022-09-05) Xie, E. B.; Simpson, Kaeley M.; Reynolds, Kristin A.; Giuliano, Ryan J.; Protudjer, Jennifer L. P.; Soderstrom, Melanie; Sauer-Zavala, Shannon; Giesbrecht, Gerald F.; Lebel, Catherine; Mackinnon, Anna L.; Rioux, Charlie; Penner-Goeke, Lara; Freeman, Makayla; Salisbury, Marlee R.; Tomfohr-Madsen, Lianne; Roos, Leslie E.
Abstract Background The prevalence of maternal depression and anxiety has increased during the COVID-19 pandemic, and pregnant individuals are experiencing concerningly elevated levels of mental health symptoms worldwide. Many individuals may now be at heightened risk of postpartum mental health disorders. There are significant concerns that a cohort of children may be at-risk for impaired self-regulation and mental illness due to elevated exposure to perinatal mental illness. With both an increased prevalence of depression and limited availability of services due to the pandemic, there is an urgent need for accessible eHealth interventions for mothers of young children. The aims of this trial are to evaluate the efficacy of the Building Emotion Awareness and Mental Health (BEAM) app-based program for reducing maternal depression symptoms (primary outcome) and improve anxiety symptoms, parenting stress, family relationships, and mother and child functioning (secondary outcomes) compared to treatment as usual (TAU). Methods A two-arm randomized controlled trial (RCT) with repeated measures will be used to evaluate the efficacy of the BEAM intervention compared to TAU among a sample of 140 mothers with children aged 18 to 36 months, who self-report moderate-to-severe symptoms of depression and/or anxiety. Individuals will be recruited online, and those randomized to the treatment group will participate in 10 weeks of psychoeducation modules, an online social support forum, and weekly group teletherapy sessions. Assessments will occur at 18–36 months postpartum (pre-test, T1), immediately after the last week of the BEAM intervention (post-test, T2), and at 3 months after the intervention (follow-up, T3). Discussion eHealth interventions have the potential to address elevated maternal mental health symptoms, parenting stress, and child functioning concerns during and after the COVID-19 pandemic and to provide accessible programming to mothers who are in need of support. This RCT will build on an open pilot trial of the BEAM program and provide further evaluation of this evidence-based intervention. Findings will increase our understanding of depression in mothers with young children and reveal the potential for long-term improvements in maternal and child health and family well-being. Trial registration ClinicalTrials.gov NCT05306626 . Registered on April 1, 2022
Open Access
Comparative Analysis of Pressure Mapping Methods in Repaired Tetralogy of Fallot: Four-Dimensional Blood Flow Hemodynamics Assessment and Development of a Novel Pressure Mapping Tool
(2023-11-14) Ihsan Ali, Safia; Garcia Flores, Julio; Myers, Kim; Lebel, Catherine
Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital heart defect (CHD) that alters normal blood flow through the heart and accounts for 10% of all CHD. Pulmonary stenosis and regurgitation are common in adults who have undergone TOF repair (rTOF) and can impact the load on the right ventricle, blood flow pressure, and pulmonary hemodynamics. Pressure mapping, obtained through 4D-flow magnetic resonance imaging (4D-flow MRI), has been applied to identify abnormal heart hemodynamics in CHD. Hence, the aim of this research was to compare pressure drop and relative pressures between patients with repaired TOF (rTOF) and healthy volunteers. An in vitro validation was performed, followed by an in vivo validation. We hypothesized that pressure drop is a more stable pressure mapping method than relative pressures to detect altered hemodynamics. A total of 36 subjects, 18 rTOF patients and 18 controls underwent cardiac MRI scans and 4D-flow MRI. Pressure drops and relative pressures in the MPA were higher in rTOF patients compared to the controls (p < 0.05). Following the in vitro validation, pressure drops proved to be a more stable pressure mapping method than relative pressures, as the flow loses its laminarity and becomes more turbulent. In conclusion, this study demonstrated that flow hemodynamics in rTOF can exhibit altered pressure maps. Pressure mapping can help provide further insight into rTOF patients’ hemodynamics to improve patient care and clinical decisions.
Open Access
Computer-Assisted Diagnosis of Genetic Syndromes Using 3D Facial Surface Scans
(2023-03-09) Bannister, Jordan J.; Forkert, Nils D.; Hallgrímsson, Benedikt; Lebel, Catherine; Bernier, Francois Paul J.
Due to the complexity and rarity of genetic syndromes, one of the primary difficulties in treating afflicted patients is diagnosing their condition. Gene technologies have been a key tool to improve diagnosis rates, but genetic testing remains inaccurate, inaccessible, or expensive for many people. Computer-assisted facial phenotyping is a complementary strategy that makes use of inexpensive and widely available technologies. Many genetic syndromes are known to be associated with altered facial morphology, and clinical geneticists often make use of facial phenotype to inform diagnoses. The overarching objective of this research was to develop clinically useful image processing algorithms and machine learning models to improve computer-assisted facial phenotyping and syndrome diagnosis systems based on 3D facial surface images. First, a fully automated 3D facial landmarking algorithm was developed to prepare 3D facial surface scans for analysis without manual labor. Next, analyses comparing different 2D and 3D facial representations were performed to determine an optimal facial image acquisition strategy. Machine learning models of 3D facial morphology were then developed to identify abnormal and characteristically syndromic faces. Additionally, an analysis of non-syndromic facial morphology was performed to present quantitative information about facial sex differences to facial surgeons. The main contributions of this thesis are the automated 3D scan processing methods and normalizing flow framework for 3D facial shape modelling that provide the computational methods needed to create a complete and highly interpretable 3D face-based computer aided diagnosis system. Additionally, results from the subject-matched analysis of 2D and 3D facial representations are the first to empirically suggest that using 3D facial imaging instead of 2D photography improves the performance of face-based syndrome diagnosis systems. Finally, the analysis performed for facial surgeons demonstrates that the methods developed in this thesis are applicable to medical domains other than computer-assisted diagnosis.
Open Access
Correction: Building Emotional Awareness and Mental Health (BEAM): study protocol for a phase III randomized controlled trial of the BEAM app-based program for mothers of children 18–36 months
(2022-09-30) Xie, E. B.; Simpson, Kaeley M.; Reynolds, Kristin A.; Giuliano, Ryan J.; Protudjer, Jennifer L. P.; Soderstrom, Melanie; Sauer-Zavala, Shannon; Giesbrecht, Gerald F.; Lebel, Catherine; Mackinnon, Anna L.; Rioux, Charlie; Penner-Goeke, Lara; Freeman, Makayla; Salisbury, Marlee R.; Tomfohr-Madsen, Lianne; Roos, Leslie E.
Open Access
Detecting neuroplastic changes in astronauts
(2023-06) Berger, Lila; Iaria, Giuseppe; Lebel, Catherine; Williams, Rebecca Jayde; Kam, Julia W. Y.
Understanding the impact of space travel on the brain has become increasingly important as the space industry plans to send humans to Mars within the next decade. Magnetic Resonance Imaging (MRI) research has indicated significant and inconsistent structural changes in the brains of astronauts as a result of spaceflight. Volumetric brain changes in astronauts have the potential to cause significant and even life-threatening consequences. Recently, research has demonstrated that reports of these volumetric changes may be corrupted by the upward shift of the brain within the skull and a redistribution of cerebrospinal fluid (CSF) resulting from microgravity. This CSF shift may create errors in the classification of the dura mater from other various tissue types, producing erroneous claims of volumetric neuroplastic brain changes resulting from spaceflight. This research was developed with the aim of reducing these classification errors through the investigation of a variety of newer MRI scans and protocols that may better account for a physical displacement of the brain and CSF in the skull. Manual tissue segmentation was performed on the standard modality to provide a comparison measure. Automated tissue segmentation was performed in each modality. Dice coefficients were calculated, and a repeated measures factorial analysis of variance was performed, followed by paired-samples t-tests. Total grey matter volume measures were obtained, and a repeated-factorial analysis of variance as well as follow up comparisons were performed for this measure as well. The primary hypothesis for this work was not confirmed, as no certain modality consistently outperformed MPRAGE across all automated software. This research may help inform modality selection for astronauts, as well as caution reporting or interpreting neuroplastic brain changes in astronauts using standard methodology.
Open Access
Early Influences on Brain Development in Preschool Children
(2021-09) Kar, Preeti; Lebel, Catherine; Pike, Bruce; McMorris, Carly
During early childhood, extensive brain development takes place which underlies foundational cognitive and behavioural learning. Early environmental factors during the prenatal period and first few postnatal years can play important roles in promoting or hindering this period of brain development. Breastfeeding in infancy and alcohol use in pregnancy are both maternal behaviors with long-term impacts on children, but their downstream effects on the brain are not well-understood during early childhood. My thesis used diffusion tensor imaging to assess white matter development in young children (2-7 years) in association with 1) breastfeeding exclusivity status at 6 months of age and the total duration of any breastfeeding, as well as 2) prenatal alcohol exposure (PAE). First, I found that breastfeeding exclusivity and duration were associated with global and regional white matter microstructure, even after controlling for perinatal and sociodemographic factors, and these findings differed by sex. Second, I found that young children with PAE showed altered white matter microstructure cross-sectionally and longitudinally compared to unexposed controls. Third, measures of white matter in motor tracts were associated with motor performance in unexposed typically developing children, but these structure-function associations were not present in young children with PAE. This work highlights the dynamic and complex brain development taking place in early childhood and indicates how environmental variables during the prenatal and postnatal period, such as breastfeeding and PAE, moderate brain circuitry and behaviors in young children. This research has broad implications for clinical, policy, and health education strategies to promote breastfeeding and prevent PAE and ultimately support mothers and children.
Open Access
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.
Open Access
Evaluation of the Associations between Prenatal Cannabis Use and Infant Developmental Outcomes at 12 Months of Age
(2023-08-29) Watts, Dana; Tomfohr-Madsen, Lianne; Chaput, Kathleen; Hill, Matthew; Lebel, Catherine
Despite warnings from governing health bodies advising against using cannabis products during preconception, pregnancy, and breastfeeding, cannabis continues to be commonly consumed by pregnant individuals. Past research has found associations between children exposed to cannabis prenatally and adverse childhood development outcomes; however, some of these studies fail to control for important confounding variables, and many are becoming outdated. Using data from the Pregnancy During the Pandemic cohort, the current project evaluated prenatal cannabis use and its association with increased risk of developmental delay across five domains: communication, gross motor, fine motor, problem-solving, and personal social skills. In addition, the association between prenatal cannabis use, birth weight, and instances of preterm birth is explored, and sociodemographic differences between cannabis users and non-users are described. Using multiple linear regression analysis, no significant associations were found between prenatal cannabis use and greater risk of infant development delay in any domain (ps > .05). Prenatal cannabis use was not associated with greater instances of preterm birth or lower birth weight. Cannabis users and non-users significantly differed on all measured sociodemographic variables.
Open Access
Examining Brain Structure after Pediatric Mild Traumatic Brain Injury
(2022-11-28) Shukla, Ayushi; Lebel, Catherine; Yeates, Keith O.; Harris, Ashley; Brooks, Brian
Mild traumatic brain injuries (mTBIs) affect millions of children annually and present a huge burden to the public health care system. mTBIs often lead to emotional, cognitive, and physical difficulties, together known as post concussive symptoms (PCS), which usually resolve within 4 weeks of injury. In up to one third of all mTBI cases, PCS can be longer lasting and are referred to as persistent PCS (PPCS). In the pediatric population, since mTBI occurs when the brain is still developing, it can lead to altered developmental trajectories, and consequently affect children's cognitive functioning, symptomatology, and quality of life. This thesis aimed to use advanced neuroimaging techniques, [i.e., diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and voxel-based morphometry (VBM)] to study unexamined aspects of brain structure associated with mTBI, PPCS, and neurocognitive outcomes after mTBI. I used DTI and NODDI to examine white matter microstructure after mTBI at different time points after injury in comparison to orthopedic injury (OI) and used VBM to examine cerebellar gray matter volume and its association to neurocognitive outcomes of mTBI. The results revealed: 1) No post-acute differences in brain structure (white matter microstructure or gray matter) between children with mTBI or OI, 2) Age moderated differential trajectories of white matter change, 3- and 6-months post-injury in symptomatic children with mTBI compared to asymptomatic children with mTBI and an OI comparison group, 3) Higher gray matter volume in the motor regions of the cerebellum 3-months after injury in the mTBI compared to the OI group, 4) Disruptions in the association between reaction time and cerebellar volume in children with mTBI. This novel set of studies provides new knowledge about brain structure following pediatric mTBI and has important implications for improving our understanding of neurobiological correlates of pediatric mTBI.