Browsing by Author "Bray, Signe L."
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Item Open Access Adolescent Mental Health: Canadian Psychiatric Risk and Outcome Study (PROCAN)- Exercise Intervention Pilot Study(2019-01-16) Corbett, Syl; Addington, Jean; MacQueen, Glenda M.; Bray, Signe L.; Swain, Mark GordonBACKGROUND: The Canadian Psychiatric Risk and Outcome Study (PROCAN), a longitudinal study of youth at risk of serious mental illness (SMI), aims to better understand the trajectory of SMI. This study was conducted as a pilot exercise intervention on a subsample of the PROCAN cohort. OBJECTIVES: The primary objective was to examine the feasibility of an exercise intervention in youth at risk of SMI. The secondary objectives were to determine whether symptoms of mental illness and memory would improve, and hippocampal volume would increase, following participation in a moderate to high intensity aerobic exercise program. METHODS: Forty-four male and female youth at risk of SMI were recruited through the PROCAN project. Participants completed clinical, cognitive, neuroimaging and fitness assessments prior to and following a sixteen-week moderate to high intensity aerobic exercise intervention. Sixty-minute exercise sessions were held three times per week. Forty-one participants completed the entire intervention and assessments, including twenty-six that completed the neuroimaging portion. Twenty-eight age and gender matched healthy controls were recruited as a baseline comparison for neuroimaging. RESULTS: Exclusion, consented, and retention rates were; 22.7, 57.6 and 93.2% respectively. Significant (p < .05) improvements in aerobic fitness (p < .0001) were achieved over the course of the intervention. Likewise, reductions in anxiety (p = .024), depression (p = .012), and general prodromal symptoms (p < .0001) occurred, however distress did not diminish (p= .131). Right whole (p < .001) and right anterior (p = .001) hippocampal volumes significantly increased. Forward Span (p = .552), Backward Span (p = 1.000) and Letter Number Span (p = .606) did not significantly change. CONCLUSION: Aerobic exercise is a feasible and sound intervention strategy for reducing symptoms and improving overall physical health, including brain health, in youth at risk for SMI. Further research is required to replicate these findings and to expand knowledge of the mechanisms, optimum dose and factors that influence the efficacy of exercise.Item Open Access Audiovisual integration in 4-and 5-year-old children: Behavioural and neural responses(2020-01) Beatch, Jacqueline Ann; Curtin, Suzanne; Protzner, Andrea; Graham, Susan A.; Bray, Signe L.; Yeung, H. HennyDynamic information in the environment often stems from multiple modalities, such as auditory and visual (audiovisual; AV). The ability to detect and integrate AV information draws attention to salient information, allows for efficient processing, and helps individuals learn sound-object associations, which can impact language development. In this dissertation, I explore stimulus characteristics that affect how AV information is integrated and processed in 4-and 5-year-olds and the relation to their receptive language (RL). In Chapter 2, I examine whether 4-and 5-year-old’s integrate AV stimuli resulting in faster and more accurately responses to matched AV compared to mismatched AV and unisensory stimuli. This was the case. I further hypothesized that responses to matching AV stimuli would predict children’s RL, which was not supported. Moreover, I hypothesized that children’s executive functioning would predict responses to mismatched stimuli, which was the case. Thus, children integrate AV information and their broader skills impact how quickly and effectively they respond to information in their environment. In Chapter 3, I use EEG to investigate 4-and 5-year-old’s processing of AV synchronous/ asynchronous human/ monkey videos. I found increased processing for mouth movements paired with vocalizations (i.e., synchronous), compared to mouth movements alone, and for auditory human, compared to monkey, vocalizations. Synchrony and species affected AV processing differently based on the modality (i.e., auditory or visual) being examined. In Chapter 4, I expand on the work in Chapter 3 to examine whether children’s neural responses are related to their RL. Here I found that 4-year-old’s processing of visual synchronous and 666ms asynchronous stimuli were related to their RL. However, no significant relation was found for the 5-year-olds. For both ages, reduced processing for auditory stimuli, iii regardless of synchrony and species, was related to higher RL. This may suggest that children who reduce processing to nonsense vocalization have more cognitive resources to process meaningful information and had higher RL. I conclude by discussing the importance of understanding the nuances of AV integration and processing in early childhood as these foundational skills are related to their development. This provides a base for future research to explore AV integration in atypical development.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 Early Life Adversity, Traits and Opioid Addiction(2018-08-14) Zumbusch, Alicia Solange; Teskey, G. Campbell; Mychasiuk, Richelle; Hill, Matthew; Bray, Signe L.Addiction has a negative impact on addicted individuals, their relationships and society at large. Though most adults have sampled addictive substances such as alcohol or prescription painkillers, only a small subset of them exhibit the chronic and relapsing drug use that characterizes addiction. Prior to compulsive and relapsing drug use, individuals will escalate their intake through increase dose or dose frequency. Given that escalation is the first hallmark of addiction to emerge, it is critical to the early detection of addiction. The increasing prevalence of synthetic and semi-synthetic opioids such as fentanyl is of critical concern as current treatments for opioid addiction are largely ineffective. Increasing focus on predisposing factors and early detection are essential to the prevention of opioid addiction. It is unknown what renders certain individuals more liable to develop addiction. Correlational research done in humans shows that there is a strong positive relationship between early life adversity and addiction prevalence in adulthood. The mechanism by which early life adversity impacts addiction vulnerability has not been well characterized. One way that early life adversity may increase the propensity to develop addiction is through the alteration of addiction-related behavioural traits. Several traits have been linked to addiction, namely impulsivity, novelty preference, anxiety and cue attraction. Human and rodent literature suggests that these traits are malleable and that stress during development can alter their expression. To date, no studies have experimentally examined the effects of early life adversity on the expression of addiction-related traits and self-administration behaviours in the same population. This thesis shows the first experimental evidence that early life adversity increases the prevalence of individuals expressing of multiple addiction risk traits as well as the number of individuals that escalate their opioid seeking and taking in a self-administration paradigm. Understanding the etiology of addiction and how early life stress augments the expression of addiction-related traits paves the way for the development of preventative interventions and knowing how early life adversity and addiction-related traits relate to the increased prevalence of opioid escalators will be beneficial to developing treatments for opioid addiction.Item Open Access The Effect of Transcranial Direct Current Stimulation on GABA and Glx in Children During Motor Learning(2019-06-07) Nwaroh, Chidera; Harris, Ashley D.; Kirton, Adam; Bray, Signe L.; Condliffe, Elizabeth G.; Dunn, Jeffrey F.Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain activity. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity but there is little information about the underlying mechanisms. Additionally, studies have shown that tDCS can affect local levels of GABA and glutamate both of which are associated with skill acquisition and plasticity. This study aimed to quantify changes in GABA and Glx in response to 5 consecutive days of anodal tDCS or high definition tDCS targeting the M1 in children. Our results suggest HD-tDCS elicits a neurochemical response that is different from anodal tDCS despite resulting in similar motor enhancements. Additionally, we identified a relationship between left sensorimotor cortex GABA and improvements in motor performance. Overall, our results suggest that the developing brain responds differently to tDCS when compared to adult literature.Item Open Access Functional Connectivity of the Anterior Cingulate Cortex in Children with Post-traumatic Headache(2020-05-19) Ofoghi, Zahra; Barlow, Karen Maria; Dewey, Deborah; Yeates, Keith Owen; Bray, Signe L.; Noel, MelaniePost-traumatic headache (PTH) is among the most common persistent post-concussion symptoms following mild traumatic brain injury (mTBI). Investigating structural and functional neuroimaging correlates of pain or headache can help to understand biological mechanisms behind persistent PTH. In this dissertation, a systematic review was conducted to examine the neuroimaging correlates of headache or pain following mTBI. Here, in the adult populations with PTH, there was evidence to suggest alterations in descending pain modulatory mechanisms but there was a lack of research in the pediatric populations with PTH. The remainder of this thesis addresses this knowledge gap by investigating alterations in central pain processing networks with a focus on the anterior cingulate cortex (ACC). To do this, functional connectivity (FC) between the ACC and other pain-related regions was explored in children with PTH and compared to those without PTH following mTBI and uninjured healthy controls. The influence of a pre-injury headache history on ACC FC was then investigated. As other cognitive and affective symptoms are also common in children with PTH, the associations between attention problems and anxiety and ACC FC were studied. Functional connectivity of the perigenual ACC-cerebellum and the subgenual ACC-DLPFC were different in children with PTH compared to healthy controls. No significant differences, however, were found in children with and without PTH. Functional connectivity between the ventral ACC areas (rostral and perigenual) and cerebellum was significantly affected by a past history of headache problems; children with PTH and a history of headache having decreased negative FC. In children with PTH, better attention performance was associated with stronger subgenual ACC-cerebellum FC. Anxiety, however, was not associated with the ACC FC and pain-related regions. Taken together, this dissertation provides evidence of alterations in descending modulatory pain processing mechanisms in children with PTH following mTBI. Further, for the first time, neuroimaging evidence supported the effect of pre-injury headaches on connectivity between pain-related regions in children with PTH. Future studies should explore FC of other pain-related regions (e.g. periaqueductal regions, cerebellum) in central pain processing networks and their relationship with recovery.Item Open Access Functional Near-Infrared Spectroscopy (fNIRS) imaging of Functional Connectivity and Task-Activity in the Cerebral Cortex of patients with mTBI(2020-09-04) Duszynski, Christopher; Dunn, Jeff F.; Bray, Signe L.; Debert, Chantel TeresaFunctional near-infrared spectroscopy (fNIRS) is a novel neuroimaging technology which has shown potential as a biomarker of mTBI. In this thesis, we developed novel easy-to-use software for analyzing measures of functional coherence and task-activity in the brain using fNIRS. We then applied this software to characterize fNIRS measures in healthy individuals, and to investigate whether fNIRS is sensitive to altered brain activity following mTBI. The software provides a full pipeline for preprocessing and utilizes wavelet analysis methods to estimate coherence, variability, phase, and power of fNIRS hemodynamic data. Using the software, we investigated the within-subject and between-subject variability of fNIRS coherence in healthy adults, finding poor-moderate between-subject reproducibility and high within-subject reliability, as well as task-effects of reduced interhemispheric coherence (IHC) and reduced power of low-frequency oscillations (LFOs) that were focused in the prefrontal brain regions during execution of a working memory task. In youth 30 days following mTBI, reduced IHC and IHC variability in the prefrontal cortex was observed during working memory, as well as a group effect of mTBI on power of LFO, compared to controls. In adults, fNIRS was used to study brain activity in pre, post, and two weeks following therapeutic repetitive transcranial magnetic stimulation (rTMS) as a treatment for persistent mTBI-related headache. In this case series, abnormal activation in the prefrontal cortex during working memory was observed on fNIRS in one subject prior to treatment which persisted at the post-treatment time point, but appeared to normalize by two weeks post-treatment, in comparison to controls, suggesting fNIRS as a potential method to study treatment effect in therapeutic rTMS trials in patients with mTBI. In this thesis, software was developed and published in the online repository GitHub, and utilized to characterize the variability and task effect in healthy individuals, informing future studies wanting to apply wavelet methodologies to investigate clinical populations. In subsequent observational studies, we observed alterations in fNIRS brain activity in pediatric patients with mTBI 1 month post-injury, as well as in an adult mTBI patient undergoing rTMS treatment, suggesting a potential role for fNIRS as an accessible technology to study mTBI-associated pathophysiology.Item Open Access In the Eye Movements of the Beholder: Manipulating Visual Scanpaths During Facial Emotion Perception Modulates Functional Brain Activation in Schizophrenia Patients and Controls(2018-10-20) Spilka, Michael; Bray, Signe L.; Goghari, Vina M.; Achim, Amélie M.; Kopala-Sibley, Daniel C.; MacMaster, Frank P.; Sears, Christopher R.Individuals with schizophrenia exhibit deficits in the ability to perceive and recognize emotions from faces, and these deficits are significant predictors of functional outcome. Research into the origins of facial emotion recognition deficits in schizophrenia has identified abnormalities in visual gaze behaviour and functional brain activation in patients during facial emotion perception; however, these two aspects of facial emotion processing have previously been studied in isolation. Nonetheless, several studies with healthy individuals and other clinical populations suggest a relationship between gaze behaviour and functional activation in regions also implicated in facial emotion processing deficits in schizophrenia (e.g., fusiform gyrus). These findings raise the important question of whether gaze behaviour abnormalities in schizophrenia contribute to reported functional activation abnormalities during facial emotion perception. In this dissertation, I examined whether manipulating visual scanpaths during facial emotion perception would modulate blood-oxygen-level dependent (BOLD) signal change in a sample of schizophrenia patients and community controls. Patients and controls underwent functional magnetic resonance imaging (fMRI) while viewing pictures of emotional faces. During the Typical Viewing condition, a fixation cue directed participants’ gaze primarily to the eyes and mouth, while gaze was directed to peripheral features during the Atypical Viewing condition. Participants additionally completed a practice version of the task outside the scanner and a traditional facial emotion discrimination task, while gaze behaviour was recorded with an eye tracker. Patients had reduced percentage of fixations to salient facial features during facial emotion discrimination, similar to previous findings. During the fMRI task, both viewing conditions elicited BOLD signal change throughout regions of the neural system for face perception. Typical Viewing led to greater activation in visual association cortex including the right “occipital face area”, while Atypical Viewing elicited greater activation in primary visual cortex and regions involved in attentional control, including the intraparietal sulcus and frontal eye fields. There were no group differences in functional activation, in contrast to previous findings. The results of this study indicate that gaze behaviour modulates activation in early face-processing regions, suggesting that abnormal gaze behaviour in schizophrenia may contribute to the documented activation abnormalities in these regions during facial emotion perception.Item Open Access Manipulating visual scanpaths during facial emotion perception modulates functional brain activation in schizophrenia patients and controls(2019-09) Spilka, Michael J.; Pittman, Daniel J.; Bray, Signe L.; Goghari, Vina M.Individuals with schizophrenia exhibit deficits in facial emotion processing, which have been associated with abnormalities in visual gaze behaviour and functional brain activation. However, the relationship between gaze behaviour and brain activation in schizophrenia remains unexamined. Studies in healthy individuals and other clinical samples indicate a relationship between gaze behaviour and functional activation in brain regions implicated in facial emotion processing deficits in schizophrenia (e.g., fusiform gyrus), prompting the question of whether a similar relationship exists in schizophrenia. This study examined whether manipulating visual scanpaths during facial emotion perception would modulate functional brain activation in a sample of 23 schizophrenia patients and 26 community controls. Participants underwent functional magnetic resonance imaging while viewing pictures of emotional faces. During the typical viewing condition, a fixation cue directed participants’ gaze primarily to the eyes and mouth, whereas during the atypical viewing condition gaze was directed to peripheral features. Both viewing conditions elicited a robust response throughout face-processing regions. Typical viewing led to greater activation in visual association cortex including the right inferior occipital gyrus/occipital face area, whereas atypical viewing elicited greater activation in primary visual cortex and regions involved in attentional control. There were no between-group activation differences in response to faces or interaction between group and gaze manipulation. The results indicate that gaze behaviour modulates functional activation in early face-processing regions in individuals with and without schizophrenia, suggesting that abnormal gaze behaviour in schizophrenia may contribute to activation abnormalities during facial emotion perception.Item Open Access Neural Correlates of Adolescent Mindfulness, Working Memory, and Internalizing Symptoms(2020-08) Stein, Jade Aurelie; Kopala-Sibley, Daniel C.; MacMaster, Frank P.; Bray, Signe L.; Tomfohr-Madsen, LianneThe central aim of this thesis was to investigate behavioural and neural associations between dispositional mindfulness, working memory, and internalizing symptoms in adolescents. One hundred and thirty-one adolescents, aged 11-18 (M = 13.76, SD = 1.65), who had a parent with a history of mood or anxiety disorders completed measures of dispositional mindfulness, internalizing symptoms, and working memory, including a functional Magnetic Resonance Imaging (fMRI) N-Back task. Hierarchal regressions and correlation analyses were performed. The blood oxygen level dependent (BOLD) signal was contrasted between 2-back versus 0-back conditions and a small volume correction was computed in the dorsolateral and ventrolateral prefrontal cortex (dlPFC, vlPFC) and the anterior cingulate cortex (ACC). Controlling for neuroticism, sex, and mindfulness experience, higher adolescent dispositional mindfulness, including higher self-acceptance and the interaction between attention and awareness and nonreactivity, related to fewer internalizing symptoms. Endorsement of attention and awareness was associated with better 2-back efficiency, except when controlling for mindfulness experience. Internalizing symptoms related to slower reaction time, controlling for sex. Significantly less BOLD signal in the right vlPFC was observed in adolescents with higher attention and awareness scores when controlling for mindfulness experience. Self-acceptance and nonreactive observing (attention and awareness x nonreactivity) may be unique components of mindfulness that have implications for adolescent internalizing symptoms. Adolescents with higher attention and awareness may require less cognitive effort when performing working memory tasks. Learning to be mindful on a daily basis may be beneficial for adolescent cognition and emotional well-being.Item Open Access Neuroplasticity in Visual Word Recognition: An Exploration of Learning-Related Behavioural and Neural Changes(2020-06-17) Cnudde, Kelsey Dawn; Protzner, Andrea; Pexman, Penny M.; Bray, Signe L.; Graham, Susan A.; Wilcox, GabrielleVisual word recognition is a cognitive process that remains relatively stable throughout adulthood. Despite this stability, recent research suggests that the system involved is malleable, by showing evidence of behavioural change after lexical decision task (LDT) practice, and of neural differences between-subjects during LDT performance. However, these studies leave the question unanswered as to whether neural change can occur within the visual word recognition system, which would suggest plasticity. We therefore investigated whether neural change accompanies the behavioural change previously found with LDT practice. If found, these neural changes could be due to processes associated with learning, where performance that is initially unskilled and effortful becomes skilled and efficient, and supported by a more specific, honed, and optimized task network. We replicated the British Lexicon Project (BLP), in which participants completed several days of LDT learning. We additionally recorded EEG at three time points to track neural change during LDT learning, and assessed event-related potentials and brain signal complexity. We found response time decreased during LDT learning, replicating the BLP. We also found neural change occurred through N170, P200, N400, and LPC amplitude effects, suggesting alterations to both the general cognitive and specific lexical processes involved in LDT performance. There was also widespread complexity decreases alongside localized increases, suggesting that with learning, LDT processing became more automatic with specific increases in processing flexibility. These findings suggest that the visual word recognition system is dynamic, flexible, and capable of undergoing plastic changes to support more efficient and automatic task performance.Item Open Access Reward Neurocircuitry in Autism Spectrum Disorder(2018-09-14) Schuetze, Manuela; Bray, Signe L.; Kennedy, Dan; Graham, Susan A.; Borgland, Stephanie Laureen; Goodyear, Bradley G.; Dewey, DeborahAutism spectrum disorder (ASD) is a common neurodevelopmental disorder with social impairments and restricted interests. Early behavioural interventions often focus on reinforcing desired behaviours (e.g., eye contact) and reducing atypical behaviours (e.g., echoing others' phrases). A recent framework suggests reward system dysfunction to be at the core of ASD symptoms. However, if the reward system is impaired in ASD, it is paradoxical that reward-based strategies are commonly used during interventions. The goal of this thesis was to investigate the reward neurocircuitry to explore whether reward system dysfunction contributes to the ASD phenotype. We conducted a literature review on physiological, behavioural, and neural responses to reinforcers to look for common atypical patterns across all domains. We then investigated structural changes in basal ganglia and the thalamus using advanced surface-based methodology. For this, we modelled effects of diagnosis, age, and their interaction on volume, shape, and surface area on T1-weighted anatomical images of 373 male participants with ASD and 384 typically developing (TD). Finally, we investigated neural responses in the context of learning using rewards that were tailored to participants’ unique interests. 27 adolescents with ASD and 31 TD adolescents performed a reinforcement learning task while we collected fMRI data. Participants had to learn which of two doors showed images of their personal interests. The literature review revealed no consistent pattern of atypical reward responses in ASD. Further, we found that subcortical regions did not differ in volume between individuals with and without ASD. However, we found localized structural changes in shape and surface area of the putamen, globus pallidus and thalamus. Some changes were modulated by age, IQ and symptom severity. Interestingly, when using personal interests as reinforcers during a learning task, we found intact learning performance and similar neural responses in the reward system between ASD and TD groups. Taken together, mixed findings from the literature review and subtle structural changes in subcortical regions of the reward system suggest a role of this neurocircuitry in the ASD phenotype. However, intact learning and typical neural responses towards individual interests suggest that the reward system is not generally impaired in ASD.Item Open Access Variability in resting-state brain networks(2020-02-03) Oliver i Alabau, Isaura; Davidsen, Jörn; Bray, Signe L.; Jackel, Brian J.; Wieser, Michael E.Recently, new studies have detected that group average brain networks display distinct organization compared with individual subject networks. In particular, each subject network presents a distinctive topology. How this variability affects the individual resting-state networks is a question we aim to solve. This is particularly important since specific resting-state networks, as the default mode network (DMN) and frontoparietal network (FPN), play an important role in early detection of neurophysiological diseases such as Alzheimer's, Parkinson, and attention-deficit hyperactivity disorder. In the analysis presented we will determine the robustness of the networks, first, and then quantify the variability in the connectivity structures. By using two distinct data sets, mapped with the same brain atlas, and three different similarity measures to infer resting-state networks, we show that the backbone of connectivity within the resting-state networks, DMN and FPN, does not vary significantly. While weaker connections do vary, they largely correspond to the links between the DMN and FPN. Overall, we find that the resting-state networks present a robust topology when a fixed atlas is used, and the recordings are sufficiently long.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.