Martin Vestergaard

White matter microstructure in superior longitudinal fasciculus associated with spatial working memory performance in children

During childhood and adolescence, ongoing white matter maturation in the fronto-parietal cortices and connecting fiber tracts is measurable with diffusion-weighted imaging. Important questions remain, however, about the links between these changes and developing cognitive functions. Spatial working memory (SWM) performance improves significantly throughout the childhood years, and several lines of evidence implicate the left fronto-parietal cortices and connecting fiber tracts in SWM processing. Here we report results from a study of 76 typically developing children, 7 to 13 years of age. We hypothesized that better SWM performance would be associated with increased fractional anisotropy (FA) in a left fronto-parietal network composed of the superior longitudinal fasciculus (SLF), the regional white matter underlying the dorsolateral pFC, and the posterior parietal cortex. As hypothesized, we observed a significant association between higher FA in the left fronto-parietal network and better SWM skills, and the effect was independent of age. This association was mainly accounted for by variability in left SLF FA and remained significant when FA measures from global fiber tracts or right SLF were included in the model. Further, the effect of FA in left SLF appeared to be mediated primarily by decreasing perpendicular diffusivity. Such associations could be related to individual differences among children in the architecture of fronto-parietal connections and/or to differences in the pace of fiber tract development. Further studies are needed to determine the contributions of intrinsic and experiential factors to the development of functionally significant individual differences in fiber tract structure.

Response inhibition is associated with white matter microstructure in children

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor cortex (preSMA), and subthalamic nucleus. Though the brains fibre tracts are known to develop during childhood, little is known about how fibre tract development within this network relates to developing behavioural control. Here we examined the relationship between response inhibition, as measured with the stop-signal task, and indices of regional white matter microstructure in typically-developing children. We hypothesized that better response inhibition performance would be associated with higher fractional anisotropy (FA) in fibre tracts within right IFG and preSMA after controlling for age. Mean FA and diffusivity values were extracted from right and left IFG and preSMA. As hypothesized, faster response inhibition was significantly associated with higher FA and lower perpendicular diffusivity in both the right IFG and the right preSMA, possibly reflecting faster speed of neural conduction within more densely packed or better myelinated fibre tracts. Moreover, both of these effects remained significant after controlling for age and whole brain estimates of these DTI parameters. Interestingly, right IFG and preSMA FA contributed additively to the prediction of performance variability. Observed associations may be related to variation in phase of maturation, to activity-dependent alterations in the network subserving response inhibition, or to stable individual differences in underlying neural system connectivity.

Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children

Sustained attention develops during childhood and has been linked to the right fronto‐parietal cortices in functional imaging studies; however, less is known about its relation to white matter (WM) characteristics. Here we investigated whether the microstructure of the WM underlying and connecting the right fronto‐parietal cortices was associated with sustained attention performance in a group of 76 typically developing children aged 7–13 years. Sustained attention was assessed using a rapid visual information processing paradigm. The two behavioral measures of interest were the sensitivity index d′ and the coefficient of variation in reaction times (RTCV). Diffusion‐weighted imaging was performed. Mean fractional anisotropy (FA) was extracted from the WM underlying right dorsolateral prefrontal (DLPFC) and parietal cortex (PC), and the right superior longitudinal fasciculus (SLF), as well as equivalent anatomical regions‐of‐interest (ROIs) in the left hemisphere and mean global WM FA. When analyzed collectively, right hemisphere ROIs FA was significantly associated with d′ independently of age. Follow‐up analyses revealed that only FA of right SLF and the superior part of the right PC contributed significantly to this association. RTCV was significantly associated with right superior PC FA, but not with right SLF FA. Observed associations remained significant after controlling for FA of equivalent left hemisphere ROIs or global mean FA. In conclusion, better sustained attention performance was associated with higher FA of WM in regions connecting right frontal and parietal cortices. Further studies are needed to clarify to which extent these associations are driven by maturational processes, stable characteristics and/or experience. Hum Brain Mapp 34:3216–3232, 2013.

Brain microstructural correlates of visuospatial choice reaction time in children.

The corticospinal tracts and the basal ganglia continue to develop during childhood and adolescence, and indices of their maturation can be obtained using diffusion-weighted imaging. Here we show that a simple measure of visuomotor function is correlated with diffusion parameters in the corticospinal tracts and neostriatum. In a cohort of 75 typically-developing children aged 7 to 13years, mean 5-choice reaction times (RTs) were assessed. We hypothesised that children with faster choice RTs would show lower mean diffusivity (MD) in the corticospinal tracts and neostriatum and higher fractional anisotropy (FA) in the corticospinal tracts, after controlling for age, gender, and handedness. Mean MD and/or FA were extracted from the right and left corticospinal tracts, putamen, and caudate nuclei. As predicted, faster 5-choice RTs were associated with lower MD in the corticospinal tracts, putamen, and caudate. MD effects on RT were bilateral in the corticospinal tracts and putamen, whilst right caudate MD was more strongly related to performance than was left caudate MD. Our results suggest a link between motor performance variability in children and diffusivity in the motor system, which may be related to: individual differences in the phase of fibre tract and neostriatal maturation in children of similar age, individual differences in motor experience during childhood (i.e., use-dependent plasticity), and/or more stable individual differences in the architecture of the motor system.

Neural correlates of taste perception in congenital olfactory impairment.

Olfaction and gustation contribute both to the appreciation of food flavours. Although acquired loss of smell has profound consequences on the pleasure of eating, food habits and body weight, less is known about the impact of congenital olfactory impairment on gustatory processing. Here we examined taste identification accuracy and its neural correlates using functional magnetic resonance imaging (fMRI) in 12 congenitally olfactory impaired individuals and 8 normosmic controls. Results showed that taste identification was worse in congenitally olfactory impaired compared to control subjects. The fMRI results demonstrated that olfactory impaired individuals had reduced activation in medial orbitofrontal cortex (mOFC) relative to normosmic subjects while tasting. In addition, olfactory performance as measured with the Sniffin Sticks correlated positively with taste-induced blood-oxygen-level dependent (BOLD) signal increases in bilateral mOFC and anterior insula. Our data provide a neurological underpinning for the reduced taste perception in congenitally olfactory impaired individuals.

State-dependent alterations in inhibitory control and emotional face identification in seasonal affective disorder.

Background: Depressed individuals often exhibit impaired inhibition to negative input and identification of positive stimuli, but it is unclear whether this is a state or trait feature. We here exploited a naturalistic model, namely individuals with seasonal affective disorder (SAD), to study this feature longitudinally. Aim: The goal of this study was to examine seasonal changes in inhibitory control and identification of emotional faces in individuals with SAD. Method: Twenty-nine individuals diagnosed with winter-SAD and 30 demographically matched controls with no seasonality symptoms completed an emotional Go/NoGo task, requiring inhibition of prepotent responses to emotional facial expressions and an emotional face identification task twice, in winter and summer. Results: In winter, individuals with SAD showed impaired ability to inhibit responses to angry (p = .0006) and sad faces (p = .011), and decreased identification of happy faces (p = .032) compared with controls. In summer, individuals with SAD and controls performed similarly on these tasks (ps > .24). Conclusion: We provide novel evidence that inhibition of angry and sad faces and identification of happy faces are impaired in SAD in the symptomatic phase, but not in the remitted phase. The affective biases in cognitive processing constitute state-dependent features of SAD. Our data show that reinstatement of a normal affective cognition should be possible and would constitute a major goal in psychiatric treatment to improve the quality of life for these patients.

Children and adolescents previously treated with glucocorticoids display lower verbal intellectual abilities

Perinatal exposure to glucocorticoids has been associated with adverse cerebral effects, but little is known about their effect on cognitive development and exposure later in childhood. This study examined intellectual abilities, memory and behavioural problems in children previously treated with glucocorticoids.

Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids

BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.

Neuroticism is linked to microstructural left-right asymmetry of fronto-limbic fibre tracts in adolescents with opposite effects in boys and girls

ABSTRACT Neuroticism is a fundamental personality trait that reflects a tendency to experience heightened negative affect and susceptibility to stress. Negative emotionality has been associated with fronto‐limbic brain structures and connecting fibre tracts. The major fibre tracts connecting the frontal and limbic brain regions are the cingulum bundle and uncinate fasciculus. We previously found that healthy adults with higher neuroticism scores had decreased left relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and uncinate fasciculus FA increases throughout childhood and into early adulthood. Since adolescence is associated with an increased incidence of anxiety and mood disorders, for which neuroticism is a known risk factor, the question arises whether the association between neuroticism and fronto‐limbic white matter microstructure asymmetry is already present in children and adolescents or whether such relationship emerges during this age period. To address this question, we assessed 72 typically‐developing 10‐to‐15 year‐olds with diffusion‐weighted imaging on a 3T magnetic resonance scanner. Neuroticism was assessed with the Junior Eysenck Personality Questionnaire. FA and parallel and perpendicular diffusivity measures were extracted for cingulum, uncinate fasciculus as well as the white matter underlying the ventromedial prefrontal cortex. Higher neuroticism scores were associated with decreased left relative to right cingulum FA in boys, while in girls, higher neuroticism scores were associated with increased left relative to right cingulum and ventromedial prefrontal white matter FA, indicating that there are sex differences in the neural correlates of neuroticism. Our findings suggest that the link between neuroticism and frontal‐limbic white matter microstructure asymmetry likely predates early adolescence. Future studies need to elucidate the significance of the observed sex differences in the neural correlates of neuroticism. HIGHLIGHTSWe examined the link between neuroticism and fronto‐limbic white matter asymmetry.Neuroticism showed a sex‐specific relationship with cingulum FA asymmetry.In boys, neuroticism was linked to decreased left relative to right cingulum FA.In girls, neuroticism was linked to increased left‐to‐right cingulum FA.The neurobiological significance of these sex differences needs to be elucidated.

Management of bleeding in major burn surgery

Major burn surgery is often associated with excessive bleeding and massive transfusion, and the development of a coagulopathy during major burn surgery is associated with increased morbidity and mortality. The aim of this study was to review the literature on intraoperative haemostatic resuscitation of burn patients during necrectomy to reveal strategies applied for haemostatic monitoring and resuscitation. We searched PubMed, EMBASE, and CENTRAL for studies published in the period 2006-2017 concerning bleeding issues related to burn surgery i.e. coagulopathy, transfusion requirements and clinical outcomes. In a broad search, a total of 1375 papers were identified. 124 of these fulfilled the inclusion criteria, and six of these were included for review. The literature confirmed that transfusion requirements increases with burn injury severity and that haemostatic monitoring by TEG® (thrombelastography) or ROTEM® (rotational thromboelastometry) significantly decreased intraoperative transfusions and was useful in predicting and goal-directing haemostatic therapy during excision surgery. Resuscitation of bleeding during major burn surgery in many instances was neither standardized nor haemostatic. We suggest that resuscitation should aim for normal haemostasis during the bleeding phase through close haemostatic monitoring and resuscitation. Randomised controlled trials are highly warranted to confirm the benefit of this concept.