scholarly journals Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis

2018 ◽  
Author(s):  
Sila Genc ◽  
Robert E Smith ◽  
Charles B Malpas ◽  
Vicki Anderson ◽  
Jan M Nicholson ◽  
...  
Keyword(s):  
White Matter ◽  
Cross Section ◽  
Repeated Measures ◽  
Pubertal Stage ◽  
Full Spectrum ◽  
Fibre Density ◽  
Fibre Development ◽  
Over Time ◽  
Time Point

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.

White matter alterations at pubertal onset

2017 ◽  
Author(s):  
Sila Genc ◽  
Marc L Seal ◽  
Thijs Dhollander ◽  
Charles B Malpas ◽  
Philip Hazell ◽  
...  
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Cross Section ◽  
Pubertal Development ◽  
B Value ◽  
Imaging Data ◽  
Pubertal Stage ◽  
Fibre Density ◽  
Pubertal Onset ◽  
Post Hoc

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.

scholarly journals Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson’s disease

2020 ◽  
Author(s):  
Angeliki Zarkali ◽  
Peter McColgan ◽  
Louise-Ann Leyland ◽  
Andrew J. Lees ◽  
Rimona S. Weil
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cross Section ◽  
Visual Function ◽  
Structural Changes ◽  
Intracranial Volume ◽  
Visual Dysfunction ◽  
Parkinsons Disease ◽  
Fibre Density

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.

scholarly journals Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis

2020 ◽  
pp. 1-11
Author(s):  
Thijs J. Burger ◽  
Frederike Schirmbeck ◽  
Jentien M. Vermeulen ◽  
Piotr J. Quee ◽  
Mariken B. de Koning ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Psychotic Disorders ◽  
Cognitive Vulnerability ◽  
Familial Risk ◽  
Related Factors ◽  
Cross Sectional ◽  
The Impact ◽  
Cognitive Alterations ◽  
Over Time

Abstract Background Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. Methods In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. Results Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. Conclusions Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

scholarly journals Not an age of depression after all? Incidence rates may be stable over time

2000 ◽  
Vol 30 (3) ◽  
pp. 489-490 ◽  
Author(s):  
E. S. PAYKEL
Keyword(s):  
Temporal Stability ◽  
Incidence Rates ◽  
Cohort Effects ◽  
Prevalence Rates ◽  
Important Paper ◽  
Period Effects ◽  
Over 40 Years ◽  
Over Time ◽  
Time Point

In an important paper in this issue Murphy et al. (pp. 503–512) report on incidence rates for depression over 40 years in the Stirling County Study. Incidence rates remained stable, contrary to most evidence that is principally based on prevalence or retrospective lifetime prevalence. Incidence rates were only a little higher in women than in men.Incidence rates are assuming increasing importance in psychiatry as they do in other areas of epidemiology. Prevalence rates are complex, depending not only on incidence of new cases of the disorder, but its persistence, and in a recurrent disorder, recurrence. Incidence rates are unbiased by these factors, a particularly valuable attribute when considering risk factors. In depression, development and widespread use of antidepressants, newer patterns of care, and in the opposite direction, increased urbanization with its accompanying social pressures, could have produced considerable changes in outcome in the last 40 years. Changes in enumerated prevalences alone could reflect changed length of episodes and rates of recurrence, so giving a misleading picture as to what has happened to the disorder.The Stirling County Study is one of the classics of epidemiology. Its originator, Alexander Leighton, is an author of the present paper with his wife, Jane Murphy, who has directed the study since the mid-1970s. Representative community samples were studied cross-sectionally in 1952, 1969 and 1992, and the previously studied samples restudied on follow-up at the later points. The design enables a separation of period effects, involving all subjects at one time point, from cohort effects. In this study similar temporal stability of prevalence has been found (Murphy et al. 2000b) to that now reported for incidence.

Bimonthly assessment of magnetization transfer magnetic resonance imaging parameters in multiple sclerosis: a 14-month, multicentre, follow-up study

2010 ◽  
Vol 16 (3) ◽  
pp. 325-331 ◽  
Author(s):  
S. Mesaros ◽  
MA Rocca ◽  
MP Sormani ◽  
P. Valsasina ◽  
C. Markowitz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Effect ◽  
Repeated Measures ◽  
Magnetization Transfer ◽  
Random Effect ◽  
Lesion Volume ◽  
Sample Sizes ◽  
Double Blind ◽  
Over Time

This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing—remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (—0.02% per visit; p = 0.14), and MTR peak height (—0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (—0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from —0.54 to —0.28, and p-values from <0.001 to 0.02). At each visit, NABT average MTR was also significantly correlated with T1-hypointense LV (average coefficient of correlation = —0.57, p < 0.001). The estimation of the sample sizes required to demonstrate a reduction of average lesion MTR (the only parameter with a significant decrease over the follow-up) ranged from 101 to 154 patients to detect a treatment effect of 50% in a 1-year trial with a power of 90%. The steady correlation observed between conventional and MT MRI measures over time supports the hypothesis of axonal degeneration of fibres passing through focal lesions as one of the factors contributing to the overall MS burden.

scholarly journals White Matter Integrity Changes and Neurocognitive Functioning in Adult-Late Onset DM1: A Follow-Up DTI Study

2021 ◽  
Author(s):  
Garazi Labayru ◽  
Borja Camino-Pontes ◽  
Antonio Jimenez-Marin ◽  
Joana Garmendia ◽  
Jorge Villanua ◽  
...  
Keyword(s):  
White Matter ◽  
Late Onset ◽  
Neurocognitive Functioning ◽  
Frontal Part ◽  
Multisystemic Disease ◽  
The Brain ◽  
Over Time ◽  
Anterior Posterior

Abstract Background: Myotonic Dystrophy Type 1 (DM1) is a multisystemic disease that affects gray and white matter (WM) tissues. WM changes in DM1 include increased hyperintensities and altered tract integrity distributed in a widespread manner. However, the precise spatiotemporal changes are yet undetermined. Methods: MRI data were acquired from 8 adult- and late-onset DM1 patients and 10 healthy controls (HC) at two different timepoints over 9.06 years. Fractional anisotropy (FA) variations were assessed with Tract-Based Spatial Statistics. Transversal and longitudinal intra- and intergroup analyses were conducted, along with correlation analyses with clinical and neuropsychological data.Results: At baseline, reduced FA values were found in patients in the uncinate, anterior-thalamic, fronto-occipital, and longitudinal tracts. At follow-up, the WM disconnection was shown to have spread from the frontal part to the rest of the tracts in the brain. Furthermore, WM lesion burden was negatively correlated with FA values, while visuo-construction and intellectual functioning were positively correlated with global and regional FA values at follow-up.Conclusion: DM1 patients showed a pronounced WM integrity loss over time compared to HC, with a neurodegeneration pattern that suggests a progressive anterior-posterior disconnection. The visuo-construction domain stands out as the most sensitive neuropsychological measure for WM microstructural impairment.

scholarly journals Longitudinal changes of ADHD symptoms in association with white matter microstructure: a tract-specific fixel-based analysis

2021 ◽  
Author(s):  
Christienne G Damatac ◽  
Sourena Soheili-Nezhad ◽  
Guilherme Blazquez Freches ◽  
Marcel P Zwiers ◽  
Sanne de Bruijn ◽  
...  
Keyword(s):  
White Matter ◽  
Fiber Density ◽  
Cross Sectional ◽  
White Matter Microstructure ◽  
Brain Structure And Function ◽  
White Matter Development ◽  
And Function ◽  
Symptom Trajectory ◽  
Over Time

Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18-34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax=1.092, standardized effect[SE]=0.044, pFWE=0.016), and improvement in combined symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax=3.775, SE=0.051, pFWE=0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations and its path may be moderated by preceding symptom trajectory.

scholarly journals Childhood conduct problems are associated with reduced white matter fibre density and morphology

2020 ◽  
Author(s):  
Daniel T. Burley ◽  
Sila Genc ◽  
Timothy J. Silk
Keyword(s):  
White Matter ◽  
Conduct Problems ◽  
Diffusion Tensor ◽  
Community Sample ◽  
Fibre Density ◽  
Time Points ◽  
White Matter Microstructure ◽  
Childhood Conduct Problems ◽  
Childhood Conduct ◽  
Time Point

AbstractChildhood conduct problems are an important public health issue as these children are at-risk of adverse outcomes. Studies using diffusion Magnetic Resonance Imaging (dMRI) have found that conduct problems in adults are characterised by abnormal white-matter microstructure within a range of white matter pathways underpinning socio-emotional processing, while evidence within children and adolescents has been less conclusive based on non-specific diffusion tensor imaging metrics. Fixel-based analysis (FBA) provides measures of fibre density and morphology that are more sensitive to developmental changes in white matter microstructure. The current study used FBA to investigate whether childhood conduct problems were related both cross-sectionally and longitudinally to microstructural alterations within the fornix, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and the uncinate fasciculus (UF). dMRI data was obtained for 130 children across two time-points in a community sample with high levels of externalising difficulties (age: time-point 1 = 9.47 – 11.86 years, time-point 2 = 10.67 −13.45 years). Conduct problems were indexed at each time-point using the Conduct Problems subscale of the parent-informant Strengths and Difficulties Questionnaire (SDQ). Conduct problems were related to lower fibre density in the fornix at both time-points, and in the ILF at time-point 2. We also observed lower fibre cross-section in the UF at time-point 1. The change in conduct problems did not predict longitudinal changes in white-matter microstructure across time-points. The current study suggests that childhood conduct problems are related to reduced fibre-specific microstructure within white matter fibre pathways implicated in socio-emotional functioning.

Abstract 14231: Effectiveness and Safety of Statin Therapy in Children: A Multi-Center, Real-World Clinical Practice Experience

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Rae Ellen W Kavey ◽  
Cedric Manlhiot ◽  
Tanveer Collins ◽  
Samuel S Gidding ◽  
Matthew Demczko ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Statin Therapy ◽  
Real World ◽  
Repeated Measures ◽  
Lifestyle Modification ◽  
Safety Data ◽  
Primary Hypercholesterolemia ◽  
Mean Compliance ◽  
Over Time

Results of statin use in clinical practice in children are very limited, with effectiveness and safety data based on short-term clinical trials. To address this, we reviewed the results of all children with primary hypercholesterolemia treated with statins for more than 6 months from 4 Pediatric Lipid Clinics. Expert Panel guidelines recommend statin if LDL-cholesterol (LDL-C) exceeds 4.9 mmol/L (190 mg/dL), or 4.1 mmol/L (160 mg/dL) with additional risk factors, after 6 months of lifestyle modification, with hepatic enzyme monitoring plus clinical surveillance and CK measurement for myositis. Patients at all study sites were managed using these guidelines. Results: There were 246 pts (59% male) who had 1488 clinical assessments. Mean age at statin initiation was 12.5±0.5 yrs. Mean duration of therapy was 2.9 yrs (IQR: 1.9_4.7) with 48% more than 3 yrs. Initial statin prescribed varied over time but 61% of pts were started on atorvastatin and 70% remained on the first statin prescribed. Mean compliance was assessed at 92% and 234 pts (94%) remained on statin therapy at the end of the review. Baseline and follow-up lab values and anthropometry (mean + SD) appear below. While 13 pts (5%) had transient AST or ALT > 3xULN, or CK >10xULN at some time during follow-up, no pt was diagnosed with myositis. In regression analysis adjusted for repeated measures over time, statin treatment was associated with significant reductions in total cholesterol, LDL-C and non-HDL-C with no change in HDL-C, TG, safety labs or anthropometry. Despite statin, 51% and 70% of pts had LDL-C levels above minimal (<3.35mmol/L; 130 mg/dL) and ideal (<2.85mmol/L; 110 mg/dL) targets at last follow-up. Conclusions: These findings in a large series of pts from real-world clinical practice show that statin therapy in children with primary hypercholesterolemia is safe and effectively lowers LDL-C on mid-term follow-up. Side effects are rare and discontinuation of treatment is uncommon.

Leadership quality: a factor important for social capital in healthcare organizations

2017 ◽  
Vol 31 (2) ◽  
pp. 175-191 ◽  
Author(s):  
Marcus Strömgren ◽  
Andrea Eriksson ◽  
Linda Ahlstrom ◽  
David Kristofer Bergman ◽  
Lotta Dellve
Keyword(s):  
Social Capital ◽  
Repeated Measures ◽  
Healthcare Organizations ◽  
Leadership Qualities ◽  
Content Type ◽  
Leadership Orientations ◽  
Leadership Quality ◽  
One Year ◽  
Over Time

Purpose The purpose of this paper is to investigate the relation between leadership and social capital and what qualities of leadership are important for social capital among employees in hospital settings over time. Design/methodology/approach A cohort of employees in hospitals answered a questionnaire at three occasions. Five small (approx. 100-bed) or mid-sized (approx. 500-bed) hospitals were included. The response rate was 54 percent at baseline (n=865), 59 percent at one-year follow-up (n=908) and 67 percent at two-year follow-up (n=632). Findings Repeated measures over time showed differences between groups in levels of social capital with respect to levels of leadership quality. Relation-oriented leadership had the strongest association with social capital. There was evidence that leadership was associated with social capital over time and that different kinds of leadership qualities were associated with social capital. Research limitations/implications This study conducted and analyzed quantitative data, and therefore, there is no knowledge of managers’ or employees’ own perceptions in this study. However, it would be interesting to compare managers’ decreased and increased leadership quality and how such differences affect social capital over time. Practical implications The findings feature the possibility for healthcare leaders to build high quality leadership as an important resource for social capital, by using different leadership orientations under different circumstances. Originality/value The paper showed that leadership was an important factor for building social capital and that different leadership qualities have different importance with respect to certain circumstances.

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