White matter alterations at pubertal onset

2017 ◽  
Author(s):  
Sila Genc ◽  
Marc L Seal ◽  
Thijs Dhollander ◽  
Charles B Malpas ◽  
Philip Hazell ◽  
...  

Recent neurodevelopmental research supports the contribution of pubertal stage to local and global grey and white matter remodelling. Little is known, however, about white matter microstructural alterations at pubertal onset. This study investigated differences in white matter properties between pre-pubertal and pubertal children using whole brain fixel-based analysis (FBA) of the microscopic density and macroscopic cross-section of fibre bundles. Diffusion-weighted imaging data were acquired for 74 typically developing children (M=10.4, SD=0.43 years, 31 female) at 3.0T (60 diffusion gradient directions, b-value=2800 s/mm 2 ). Group comparisons of fibre density (FD) and fibre cross-section (FC) were made between age-matched pre-pubertal and pubertal groups, and post-hoc analyses were performed on regions of interest (ROIs) defined in the splenium, body and genu of the corpus callosum. Significant fixel-wise differences in FD were observed between the pubertal groups, where the pubertal group had significantly higher FD compared with age-matched pre-pubertal children, localised to the posterior corpus callosum. Post-hoc analyses on mean FD in the corpus callosum ROIs revealed group differences between the pubertal groups in the splenium, but not body or genu. The observed higher apparent fibre density in the splenium suggests that pubertal onset coincides with white matter differences explained by increasing axon diameter. This may be an important effect to account for over pubertal development, particularly for group studies where age-matched clinical and typical populations may be at various stages of puberty.

2018 ◽  
Author(s):  
Sila Genc ◽  
Robert E Smith ◽  
Charles B Malpas ◽  
Vicki Anderson ◽  
Jan M Nicholson ◽  
...  

AbstractPurposeWhite matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time.MethodsDiffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 – 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach.ResultsThere was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison.ConclusionUsing a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.


2019 ◽  
Author(s):  
Sila Genc ◽  
Charles B Malpas ◽  
Alisha Gulenc ◽  
Emma Sciberras ◽  
Daryl Efron ◽  
...  

ABSTRACTThe pubertal period involves dynamic white matter development. This period also corresponds with rapid gains in higher cognitive functions including attention, as well as increased risk of developing mental health difficulties. This longitudinal study comprised children aged 9-13 years (n=130). Diffusion magnetic resonance imaging (dMRI) data were acquired (b=2800 s/mm2, 60 directions) at two time-points. We derived measures of fibre density and morphology using the fixel-based analysis framework and performed a tract-based mixed-effects modelling analysis to understand patterns of white matter development with respect to age, pubertal stage, attentional difficulties, and internalising and externalising problems. We observed significant increases in apparent fibre density across a large number of white matter pathways, including major association and commissural pathways. We observed a linear relationship between fibre density and morphology with pubertal stage, in the right superior longitudinal fasciculus and in the right inferior longitudinal fasciculus. In terms of symptom severity, fibre density was positively associated with attentional dysfunction in the right uncinate fasciculus. Overall, white matter development across ages 9-13 years involved the expansion of major white matter fibre pathways, with key right-lateralised association pathways linked with pubertal development and attentional difficulties.


2017 ◽  
Author(s):  
Sila Genc ◽  
Charles B Malpas ◽  
Gareth Ball ◽  
Timothy J Silk ◽  
Marc L Seal

AbstractPurposeThe corpus callosum is integral to the central nervous system, and continually develops with age by virtue of increasing axon diameter and ongoing myelination. Magnetic resonance imaging (MRI) techniques offer a means to disentangle these two aspects of white matter development. We investigate the profile of microstructural metrics across the corpus callosum, and assess the impact of age, sex and pubertal development on these processes.MethodsThis study made use of two independent paediatric populations. Multi-shell diffusion MRI data were analysed to produce a suite of diffusion tensor imaging (DTI), neurite orientation density and dispersion imaging (NODDI), and apparent fibre density (AFD) metrics. A multivariate profile analysis was performed for each diffusion metric across 10 subdivisions of the corpus callosum.ResultsAll diffusion metrics significantly varied across the length of the corpus callosum. AFD exhibited a strong relationship with age across the corpus callosum (partial η2 = .65), particularly in the posterior body of the corpus callosum (partial η2 = .72). In addition, females had significantly higher AFD compared with males, most markedly in the anterior splenium (partial η2 = .14) and posterior genu (partial η2 = .13). Age-matched pubertal group differences were localised to the splenium.ConclusionWe present evidence of a strong relationship between apparent fibre density and age, sex, and puberty during development. These results are consistent with ex vivo studies of fibre morphology, providing insights into the dynamics of axonal development in childhood and adolescence using diffusion MRI.Target journalsBrain Structure & Function; HBM; NeuroImage; Developmental Cognitive Neuroscience


2020 ◽  
Vol 17 (10) ◽  
pp. 967-975
Author(s):  
Hyun-Ju Kim ◽  
Minji Bang ◽  
Kang Soo Lee ◽  
Tai Kiu Choi ◽  
Chun Il Park ◽  
...  

Objective The brain-derived neurotrophic factor (<i>BDNF</i>) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with <i>BDNF</i> Val66Met polymorphism in PD.Methods Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics.Results The GG genotype in <i>BDNF</i> Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II.Conclusion Our findings demonstrate that the <i>BDNF</i> Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.


2020 ◽  
Author(s):  
Claire E Kelly ◽  
Deanne K Thompson ◽  
Sila Genc ◽  
Jian Chen ◽  
Joseph YM Yang ◽  
...  

AbstractBackgroundIt is well documented that infants born very preterm (VP) are at risk of brain injury and altered brain development in the neonatal period, however there is a lack of long-term, longitudinal studies on the effects of VP birth on white matter development over childhood. Most previous studies were based on voxel-averaged, non-fibre-specific diffusion magnetic resonance imaging (MRI) measures, such as fractional anisotropy. In contrast, the novel diffusion MRI analysis framework, fixel-based analysis (FBA), enables whole-brain analysis of microstructural and macrostructural properties of individual fibre populations at a sub-voxel level. We applied FBA to investigate the long-term implications of VP birth and associated perinatal risk factors on fibre development in childhood and adolescence.MethodsDiffusion images were acquired for a cohort of VP (born <30 weeks’ gestation) and full-term (FT, ≥37 weeks’ gestation) children at two ages: mean (SD) 7.6 (0.2) years (n=138 VP and 32 FT children) and 13.3 (0.4) years (n=130 VP and 45 FT children). 103 VP and 21 FT children had images at both ages for longitudinal analysis. At every fixel (individual fibre population within an image voxel) across the white matter, we compared FBA metrics (fibre density (FD), cross-section (FC) and a combination of these properties (FDC)) between VP and FT groups cross-sectionally at each age, and longitudinally between ages. We also examined associations between perinatal risk factors and FBA metrics in the VP group.ResultsCompared with FT children, VP children had lower FD, FC and FDC throughout the white matter, particularly in the corpus callosum, tapetum, inferior fronto-occipital fasciculus, fornix and cingulum at ages 7 and 13 years, as well as the motor pathways at age 13 years. VP children also had slower FDC development in the corpus callosum and corticospinal tract between ages 7 and 13 years compared with FT children. Within VP children, earlier gestational age at birth, lower birth weight z-score, and neonatal brain abnormalities were associated with lower FD, FC and FDC throughout the white matter at both ages.ConclusionsVP birth and concomitant perinatal risk factors are associated with fibre tract-specific alterations to axonal development in childhood and adolescence.


2020 ◽  
Author(s):  
Wen-jie Shi ◽  
Tai-peng Sun ◽  
Li-rong Zhuang ◽  
Hua Feng ◽  
Peng Yan ◽  
...  

Abstract BackgroundDeficit schizophrenia (DS) is a set of highly homogenous schizophrenia subtypes characterized by primary and persistent negative symptoms. Previous research studies have found that the negative symptoms of schizophrenia are closely related to the impairment of brain structure and function.This study seeks to explore the characteristics of white matter in schizophrenic patients with defective or non-defective symptoms by diffuse tensor imaging (DTI).MethodsAccording to the defective schizophrenia diagnostic criteria and ICD-10 diagnostic criteria, 30 patients with DS and 30 patients with non-defective schizophrenia (NDS) were enrolled into the research study. DTI imaging data of the white matter were collected by 1.5T magnetic resonance imaging scanner. Then a tract-based spatial statistics (TBSS) method was used to compare the fractional anisotropy (FA) values of the white matter fiber between the two groups.ResultsThe TBSS analysis results showed that the FA values in the right side of the knee of the corpus callosum (MNI:14,36,-7), right anterior radio-coronal region (MIN:11,34,3) and the right hippocampal region (MIN:30,34,16) in the DS patients were significantly lower compared with those of the NDS patients (all p<0.05). The FA values in the right side of the knee of the corpus callosum was significantly correlated with the time from onset to treatment (r=−0.350, p<0.001), PANSS-negative symptom score (r=−0.157, p=0.007). The FA values in the right anterior radio-crown region was positively correlated with PANSS-negative symptom score (r=0.306, p=0.048). The right hippocampus was negatively correlated with years of education (r=−0.614, p=0.020), duration of antipsychotics using(r=−0.140, p= 0.022), and PANSS-negative symptom score (r=−0.637, p=0.040).ConclusionsIn schizophrenic patients with defective symptoms, the structural integrity of white matter fibers was more seriously damaged in the three brain regions including the right knee of the corpus callosum, the right anterior region of the right radiative crown, and the right hippocampus. These white matter lesions are closely related to patient characteristics such as years of education, duration from onset to treatment, duration of anti-psychotic, and severity of negative symptoms.


2020 ◽  
Vol 45 ◽  
pp. 100853 ◽  
Author(s):  
Sila Genc ◽  
Charles B. Malpas ◽  
Alisha Gulenc ◽  
Emma Sciberras ◽  
Daryl Efron ◽  
...  

2020 ◽  
Author(s):  
Angeliki Zarkali ◽  
Peter McColgan ◽  
Louise-Ann Leyland ◽  
Andrew J. Lees ◽  
Rimona S. Weil

Visual dysfunction predicts dementia in Parkinsons disease (PD), but whether this translates to structural change is not known. We aimed to identify longitudinal white matter changes in patients with Parkinsons disease and low visual function and also in those who developed mild cognitive impairment (MCI). We used fixel-based analysis to examine longitudinal white matter change in PD. Diffusion MRI and clinical assessments were performed in 77 patients at baseline (22 low visual function /55 intact vision; and 13 MCI, 13 MCI converters /51 normal cognition) and 25 controls and again after 18 months. We compared micro-structural changes in fibre density, macro-structural changes in fibre bundle cross-section (FC) and combined fibre density and cross-section across white matter, adjusting for age, gender and intracranial volume. Patients with Parkinsons and visual dysfunction showed worse cognitive performance at follow up and were more likely to develop MCI compared with those with normal vision (p=0.008). Parkinsons with poor visual function showed diffuse micro-structural and macro-structural changes at baseline, whereas those with MCI showed fewer baseline changes. At follow-up, Parkinsons with low visual function showed widespread macrostructural changes, involving the fronto-occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in baseline MCI or in MCI converters, even when the two groups were combined. Parkinsons patients with poor visual function show increased white matter damage over time, providing further evidence for visual function as a marker of imminent cognitive decline.


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