Browsing by Author "Lebel, Catherine A."
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Item Open Access 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.Item Open Access Assessment of T2 Magnetic Resonance Relaxation as an Imaging Biomarker of Normal Brain Aging over the Adult Lifespan(2021-01-11) Wang, Xing; Frayne, Richard; Lebel, Catherine A.; McCreary, Cheryl R.Quantitative T2 relaxation time (qT2) was proposed for assessing brain tissue changes. In this study, qT2 was evaluated to examine normal brain aging across the adult lifespan. I explored the specific hypotheses that 1) short- (weeks) and long-term (years) qT2 repeatability were equivalent, and 2) qT2 increased with age-related increases in tissue water content and demyelination but decreased with increased iron accumulation. The repeatability assessment found qT2 estimation robust over >4 years. Long-term was similar to, but worse than short-term repeatability. A quadratic regression model was determined to be the best fitting analytical model. Linear mixed effects models were used to evaluate qT2 changes with age in twelve regions and qT2 change rates from six regions compared against a reference region. The results supported the hypothesis that qT2 increases with age; however, could not demonstrate that these T2 changes result from changes in tissue water content, demyelination or iron accumulation.Item Open Access Brain Structural and Functional MRI of Patients with Inflammatory Bowel Disease(2019-05-30) Heidari, Faranak; Goodyear, Bradley Gordon; Swain, Mark Gordon; Lebel, Catherine A.; Kaplan, Gilaad G.; Callahan, Brandy L.Inflammatory bowel disease (IBD) is a highly-disabling and painful, chronic immune-mediated inflammatory disease (IMID) of the bowel, with an annual incidence and prevalence that continue to rise. IBD diagnosis commonly occurs during young adulthood, and thus greatly impacts an individual’s productivity, leading to substantial economic burden. IBD patients can also experience behavioral symptoms, including mood and sleep disorders, depression and fatigue. While medication and surgery successfully alleviate somatic symptoms, they only partially treat behavioral symptoms. In fact, these symptoms are often considered as emotional reactions to illness and are left untreated, diminishing the quality-of-life of patients and complicating their clinical management. Evidence suggests that these symptoms have a neurological basis, as a result of the impact of inflammatory responses on gut-to-brain signalling pathways. In this thesis, magnetic resonance imaging (MRI) techniques were used to compare the structure and function of brain regions and networks in IBD patients, relative to control subjects. Regions of the basal ganglia exhibited greater volume and decreased susceptibility (a potential indicator of decreased metabolism) in IBD patients. Altered functional connections between these regions as well as connections with motor-related and cognitive areas were also observed. Given the association between the observed regions and symptoms commonly experienced by IBD patients, our studies suggest there is indeed a neurological component to observed IBD-related symptoms. Future longitudinal studies to examine treatment response and specific behavioral domains are warranted, to fully elucidate the interaction between the brain and inflammatory processes in the setting of IBD.Item Open Access Brain Structure and Mental Health in Typically Developing Youth and Those with Prenatal Alcohol Exposure and Postnatal Adversities(2019-08-14) Andre, Quinn; Lebel, Catherine A.; Goodyear, Bradley Gordon; Giesbrecht, G. F.Mental health problems are linked to brain structural changes, primarily in the limbic system and prefrontal cortex, and commonly emerge in adolescence. Although progress has been made in understanding mental health disorders, there are still gaps in mental health research in pediatric typically-developing cohorts. Research clarifying the underlying mental health-related biomarkers aids in recognition and treatment of mental health problems and builds a foundation for studying other populations, such as those with neurodevelopmental disorders. Prenatal alcohol exposure (PAE) can broadly impact development, including brain structure and mental health. Nearly all individuals with PAE suffer from comorbid mental health disorders, yet little is known about altered brain structure and mental health in youth with PAE. To assess brain structure, structural magnetic resonance imaging (MRI) was used, specifically T1-weighted and diffusion-weighted imaging to measure anatomical volumes and properties of white matter, respectively. Internalizing and externalizing behaviours, negative behaviours directed either internally or externally, respectively, were used to assess symptoms relevant to mental health. In a typical-development cohort, lower mean diffusivity (MD) and higher fractional anisotropy (FA) measures in the cingulum and uncinate were the main underlying biomarkers for internalizing and externalizing behaviours. In the PAE study, youth with PAE showed significantly reduced volumes of the anterior cingulate cortex, superior frontal gyrus, and reduced FA in the cingulum and uncinate compared to controls. Youth with PAE and additional postnatal exposures exhibited similar brain structure to controls (i.e. volumes, FA and MD values), except in MD of the fornix. Both groups with PAE (with or without postnatal exposure) demonstrated higher externalizing behaviours than controls. Between group differences in mental health-brain structure relationships were found in both limbic gray and white matter. Together this research informs brain structure and mental health relationships in two important groups. With an understanding of typical development, a better understanding of the altered trajectories in PAE can be evaluated, and by having a more robust characterization of youth with PAE, improved services and interventions can be provided.Item Open Access Brain white matter structure and language ability in preschool-aged children(2018-01) Walton, Matthew; Dewey, Deborah; Lebel, Catherine A.Brain alterations are associated with reading and language difficulties in older children, but little research has investigated relationships between early language skills and brain white matter structure during the preschool period. We studied 68 children aged 3.0-5.6 years who underwent diffusion tensor imaging and participated in assessments of Phonological Processing and Speeded Naming. Tract-based spatial statistics and tractography revealed relationships between Phonological Processing and diffusion parameters in bilateral ventral white matter pathways and the corpus callosum. Phonological Processing was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity. The relationships observed in left ventral pathways are consistent with studies in older children, and demonstrate that structural markers for language performance are apparent as young as 3 years of age. Our findings in right hemisphere areas that are not as commonly found in adult studies suggest that young children rely on a widespread network for language processing that becomes more specialized with age.Item Open Access A comparison of inhomogeneous magnetization transfer, myelin volume fraction, and diffusion tensor imaging measures in healthy children(2017-09-12) Geeraert, Bryce L.; Lebel, Robert Marc; Mah, Alyssa C.; Deoni, Sean C. L.; Alsop, David C.; Varma, Gopal; Lebel, Catherine A.Sensitive and specific biomarkers of myelin can help define baseline brain health and development, identify and monitor disease pathology, and evaluate response to treatment where myelin content is affected. Diffusion measures such as radial diffusivity (RD) are commonly used to assess myelin content, but are not specific to myelin. Inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) offer quantitative parameters (qihMT and myelin volume fraction/VFm, respectively) which are suggested to have improved sensitivity to myelin. We compared RD, qihMT, and VFm in a cohort of 23 healthy children aged 8-13 years to evaluate the similarities and differences across these measures. All 3 measures were significantly related across brain voxels, but VFm and qihMT were significantly more strongly correlated (qihMT-VFm r = 0.89) than either measure was with RD (RD-qihMT r = -0.66, RD-VFm r = -0.74; all p < 0.001). Mean parameters differed in several regions, especially in subcortical gray matter. These differences can likely be explained by unique sensitivities of each measure to non-myelin factors, such as crossing fiber geometry, axonal packing, fiber orientation, glial density, or magnetization transfer effects in a voxel. We also observed an orientation dependence of qihMT in white matter, such that qihMT decreased as fiber orientation went from parallel to perpendicular to B0. All measures appear to be sensitive to myelin content, though qihMT and VFm appear to be more specific to it than RD. Scan time, noise tolerance, and resolution requirements may inform researchers of the appropriate measure to choose for a specific application.Item Open Access Early Language Abilities and the Underlying Neural Functional Reading Network in Preschoolers(2018-06-25) Benischek, Alina Marie; Lebel, Catherine A.; Dewey, Deborah; Bray, Signe L.; Graham, Susan A.Early childhood is a critical time for language development. Language impairments that go untreated in the early years can result in decreased academic achievement and future mental health concerns. Despite the importance of early language development, very little research has focused on the functional brain systems supporting language in typically developing young children. We investigated relationships between age, language abilities, and the brain’s functional connectivity (FC) patterns seeded from brain areas associated with reading. The study included 50 healthy children aged 2.9-5.6 years (3.8 ± 0.6 years, 21f/29m) who completed a language assessment (NEPSY-II Phonological Processing and Speeded Naming) and underwent functional MRI (magnetic resonance imaging) scanning while watching a movie. Phonological Processing scores positively correlated with FC between the left angular gyrus and contralateral sensorimotor cortices, as well as between the right angular gyrus and the left supramarginal gyrus. Speeded Naming scores positively correlated with FC between the left inferior frontal gyrus, pars triangularis and the left fusiform gyrus, extending to the posterior region of the middle/inferior temporal gyrus and negatively correlated with the precuneus of the default mode network. Despite these variations in the FC patterns associated with speeded naming and phonological processing, both language measures positively correlated with FC between the ROI and the angular gyrus, supramarginal gyrus, and precentral gyrus. Age positively correlated with FC between regions within the ventral language pathway, including the inferior frontal gyrus and middle/inferior temporal gyrus and negatively correlated with FC between ipsilateral language regions and contralateral visual areas within the occipital cortex. The results demonstrate that better language abilities in young children are associated with stronger functional connections between brain regions within the language network identified in older children and adults who can perform more complex language processes.Item Open Access Late Childhood Refinements of White Matter Microstructure and Links to Reading(2020-01-03) Geeraert, Bryce Landon; Lebel, Catherine A.; Frayne, Richard; Yeates, Keith OwenLate childhood and adolescence is a fascinating period of brain development where many sophisticated cognitive skills such as reading are refined. Complex functions like reading are performed by networks of cortical regions connected by white matter tracts. White matter development and links to reading have been well-studied using diffusion tensor imaging (DTI), but DTI lacks both specificity and accuracy. The tensor model is simultaneously sensitive to many white matter microstructural features, and cannot account for complex fiber architecture. Neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT), and multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) have increased specificity to individual aspects of white matter microstructure. This study sought to leverage advanced imaging methods to build upon the foundation of DTI-based investigations of white matter development and links to reading. Our first aim was to compare the sensitivity of mcDESPOT and ihMT myelin markers to DTI measures, as no previous studies have evaluated the practicality of these techniques in the human brain. Next, we applied NODDI, ihMT, and mcDESPOT alongside DTI to describe development of white matter microstructure during late childhood and adolescence. Finally, white matter microstructure was linked to reading through a cross-sectional principal component analysis and investigations of longitudinal changes in white matter and reading. In this way we identified key components of white matter microstructure and linked microstructural development to reading acquisition. This study has shed new light on the microstructural nuances of white matter development and cognitive refinements occurring during late childhood and adolescence.Item Open Access Mild Traumatic Brain Injury, Sleep, and Pain in Adolescence(2018-11-14) Christensen, Jennaya; Mychasiuk, Richelle; Antle, Michael C.; Noel, Melanie; Lebel, Catherine A.The child and adolescent age group exhibit the highest rates of traumatic brain injury (TBI), with mild TBI (mTBI) and repetitive mild TBI (RmTBI) accounting for a large proportion of these injuries. Adolescents represent a particularly high risk cohort for experiencing long-term post-traumatic deficits. During this critical development phase, dramatic changes in brain structure and organization coincide with important shifts in the sleep cycle, which predispose adolescents to sleep deprivation. Similarly, mTBI often leads to reports of varying levels of sleep problems, yet the role of post-traumatic sleep in post-concussive symptomology remains unclear. Therefore, it is possible that sleep deprivation in the post-traumatic period could be further exacerbating the deleterious effects of mTBI. The glymphatic system is the central nervous system’s (CNS) macroscopic waste clearance system. Importantly, this system removes neurotoxic waste, such as Tau and β-amyloid, from the CNS. Recent developments have determined that the glymphatic system is 90% more active during sleep states while being dramatically suppressed during wakefulness. Given that Tau and β-amyloid protein aggregates are pathological trademarks of the neurodegenerative disorders that are associated with RmTBI and that mTBI patients commonly report sleep problems, one would reason that a reduced glymphatic clearance function may play an imperative role in the development of the neurological deficits related to RmTBI. Chronic pain and sleep deprivation represent major health issues that plague adolescence. A bidirectional relationship exists between sleep and pain; however, emerging evidence suggests that sleep disturbances have a stronger influence on subsequent pain than vice versa. The neurobiological underpinnings of this relationship, particularly during adolescence, are poorly understood. Given the high prevalence of these health issues during adolescence and the debilitating effects they inflict on nearly every domain of development, it is crucial that we determine the neurobiological mechanisms fundamental to this relationship and identify potential therapeutic strategies.Item Open Access Neuroanatomical Changes Associated with Working Memory Training in Healthy Adults(2018-06-26) Savage, Linette; Goghari, Vina M.; Campbell, Tavis S.; Bodner, Glen E.; Lebel, Catherine A.; MacMaster, Frank P.; Yang, LixiaThe potential for working memory training to enhance cognitive and intellectual abilities is alluring across scientific disciplines and the general public. However, the field has been fraught with inconsistency and controversy. Heterogeneous methodological implementations have led to a divided and contrasting body of literature, which has collectively limited scientific transparency and advancement in the field. However, neuroimaging has the potential to clarify what, if any, benefit working memory training has on the adult human brain. A recent series of studies used functional neuroimaging to investigate neural activations associated with working memory training. This dissertation uses structural imaging to address another theoretical area: the neuroanatomical correlates of working memory training. Forty-eight healthy community dwelling adults, aged 18 - 40 years, completed a series of cognitive tasks and underwent magnetic resonance imaging (MRI) before and after completing a 6-week trial of working memory training (experimental condition) or processing speed training (active control condition). Group by time repeated measures Analyses of Variance (rm-ANOVAs) were conducted on MRI data to identify changes in surface area, thickness, and volume in theoretically relevant gray matter regions of interest, as well as overall gray and white matter volumes, associated with working memory training. Similar analyses were conducted to investigate changes in cognitive task performance in this sample. Null results were present across all neuroanatomical metrics after correction for multiple comparisons, and findings from cognitive tasks were consistent with the subset of literature suggesting that working memory training does not meaningfully benefit cognitive performance. Albeit limited by low statistical power and the confines of available technology, findings of this study, in consort with recently published investigations, strongly support the idea that working memory training is not an effective method for enhancing cognitive performance or inducing neoplastic changes in brain structure. We suggest that future studies continue attempts to resolve heterogeneity and polarization in this field, or alternatively, concentrate resources on identifying and refining mechanisms of change in populations who may benefit from rehabilitative forms of cognitive training.Item Open Access Neurophysiological and diffusion tensor imaging correlates of mild traumatic brain injury in children(2018-07-24) King, Regan; Kirton, Adam; Barlow, Karen; Lebel, Catherine A.; Esser, Michael J.; Federico, PaoloChildren typically recover quickly following a mild traumatic brain injury (mTBI), however up to 15% of children continue to experience symptoms past three months post injury. Currently, underlying mechanisms of persistent post-concussive symptoms (PPCS) in children are unknown. The present thesis uses transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) to characterize the structural and functional characteristics of PPCS in 98 children (aged 8-18) with mTBI, over time. The Post-concussive Symptom Inventory (PCSI) was used to classify post-concussive symptoms in participants as symptomatic or asymptomatic. Twenty-six healthy controls were included for comparison. Neurophysiological data assessing cortical inhibition and facilitation were evaluated alongside symptom status. Associations between symptom status and DTI measures of water diffusion and anisotropy were also assessed in the corticospinal tract (CST), motor fibers of the corpus callosum (CC), and uncinate fasciculus (UF). Differences in neurophysiology were noted between healthy controls and children with mTBI in both inhibitory and excitatory TMS paradigms, further differentiating by symptom status. Differences in inhibitory paradigms were also noted over time. Fractional anisotropy (FA) differed as well in the UF, but not in the CST or CC, of symptomatic children compared to controls. No differences in diffusion metrics were observed over time. In summary, these findings suggest an indirect association of neurophysiology and white matter structure in mTBI recovery. Further exploration of neurophysiological and imaging correlates of PPCS are required to improve recovery and treatment outcomes of mTBI.Item Embargo White matter development and neurodevelopmental abnormalities(2020-04-23) Dimond, Dennis Louis; Bray, Signe L.; Lebel, Catherine A.; Sears, Christopher R.; Silk, Timothy J.; Dunn, Jeff F.White matter undergoes profound growth over the course of neurodevelopment, with maturational changes in properties such as axon orientation dispersion, axon/neurite density, and the cross-sectional diameter of axon fiber bundles. These changes are believed to be important for cognitive-behavioral maturation. Such maturation is particularly rapid during early childhood, though how specific white matter properties develop during this period is unclear. Early childhood is also a period wherein symptoms of neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), become more prominent. Atypical white matter maturation is theorized to contribute to cognitive-behavioral deficits in ASD at later stages of development, though determining the specific structural properties and anatomical location of abnormalities has been challenging. The overall goal of this thesis was to characterize developmental trajectories of specific white matter properties during early childhood and determine if these properties are abnormal in ASD and underlie core behavioral deficits. To achieve this goal, I conducted two studies in children ages 4-8 years investigating developmental changes in 1) axonal orientation dispersion and neurite density, and 2) axon density and fiber bundle cross-sectional size. Building off these studies, I then investigated abnormalities in axon density and fiber cross-section in adolescents-adults with ASD and explored their relation to social difficulties. I found that metrics sensitive to neurite/axon density and fiber cross-section, but not axon orientation dispersion increased profoundly in most fiber bundles during early childhood. Some overlapping temporospatial maturation trends were observed across metrics, though each followed relatively unique trajectories. A metric sensitive to axon density was reduced globally and in specific fiber bundles in ASD; more severe reductions in the major interhemispheric tract of the brain predicted greater social difficulties. Findings from this thesis suggest that early childhood is an important period for axon/neurite density and tract macrostructural growth, with heterochronous change in these properties. Findings in ASD suggest maturation of axon density may go astray prior to adolescence – potentially in early childhood, infancy or fetal development – and contribute to behavioral deficits. This evidence has broad implications to understanding typical and atypical white matter development and how changes in specific structural features contribute to cognitive-behavioral maturation.Item Open Access 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.