White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term‐born and 56 very preterm and/or low birth weight (VP/VLBW, < 32 weeks of gestation and/or birth weight < 1,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity—AD, RD, MD, fractional anisotropy—FA) in the whole CST and slice‐wise along the CST. Additionally, we used the automatic, tract‐based‐spatial‐statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice‐wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long‐term structural WM changes induced by premature birth. Hum Brain Mapp 37:289–299, 2016. © 2015 Wiley Periodicals, Inc.     

Language ability in preterm children is associated with arcuate fasciculi microstructure at term

In the mature human brain, the arcuate fasciculus mediates verbal working memory, word learning, and sublexical speech repetition. However, its contribution to early language acquisition remains unclear. In this work, we aimed to evaluate the role of the direct segments of the arcuate fasciculi in the early acquisition of linguistic function. We imaged a cohort of 43 preterm born infants (median age at birth of 30 gestational weeks; median age at scan of 42 postmenstrual weeks) using high b value high‐angular resolution diffusion‐weighted neuroimaging and assessed their linguistic performance at 2 years of age. Using constrained spherical deconvolution tractography, we virtually dissected the arcuate fasciculi and measured fractional anisotropy (FA) as a metric of white matter development. We found that term equivalent FA of the left and right arcuate fasciculi was significantly associated with individual differences in linguistic and cognitive abilities in early childhood, independent of the degree of prematurity. These findings suggest that differences in arcuate fasciculi microstructure at the time of normal birth have a significant impact on language development and modulate the first stages of language learning. Hum Brain Mapp 38:3836–3847, 2017. © 2017 Wiley Periodicals, Inc.     

Mapping the neuroanatomical impact of very preterm birth across childhood

Those born very preterm (VPT; <32 weeks gestational age) have an increased risk in developing a wide range of cognitive deficits. In early‐to‐late childhood, brain structure has been shown to be altered in VPT compared to full‐term (FT) children; however, the results are inconsistent. The current study examined subcortical volumes, cortical thickness, and surface area in a large cohort of VPT and FT children aged 4–12 years. Structural magnetic resonance imaging (MRI) was obtained on 120 VPT and 146 FT children who returned up to three times, resulting in 176 VPT and 173 FT unique data points. For each participant, Corticometric Iterative Vertex‐based Estimation of Thickness was used to obtain global measurements of total brain, cortical grey and cortical white matter volumes, along with surface‐based measurements of cortical thickness and surface area, and Multiple Automatically Generated Templates (MAGeT) brain segmentation tool was used to segment the subcortical structures. To examine group differences and group–age interactions, mixed‐effects models were used (controlling for whole‐brain volume). We found few differences between the two groups in subcortical volumes. The VPT children showed increased cortical thickness in frontal, occipital and fusiform gyri and inferior pre–post–central areas, while thinning occurred in the midcingulate. Cortical thickness in occipital regions showed more rapid decreases with age in the VPT compared to the FT children. VPT children also showed both regional increases, particularly in the temporal lobe, and decreases in surface area. Our results indicate a delayed maturational trajectory in those born VPT.     

Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight

Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (>2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent‐reported metacognition scores overall (P = 0.008) and better self‐reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects. Hum Brain Mapp 36:1138–1150, 2015. © 2014 Wiley Periodicals, Inc.     

Visual perception and visual-motor integration in very preterm and/or very low birth weight children: a meta-analysis

A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual perceptive and visual-motor integration abilities. Very preterm born children showed deficits in visual-spatial abilities (medium to large effect sizes) but not in visual closure perception. Tests reporting broad visual perceptive indices showed inconclusive results. In addition, impaired visual-motor integration was found (medium effect size), particularly in boys compared to girls. The observed visual-spatial and visual-motor integration deficits may arise from affected occipital-parietal-frontal neural circuitries.     

Altered functional connectivity during face processing in children born with very low birth weight

Structural brain alterations have been reported in key emotional face processing regions following preterm birth; however, few studies have investigated the functional networks underlying these processes in children born with very low birth weight (VLBW). Using magnetoencephalography (MEG), we examined the functional networks related to the implicit processing of happy and angry faces in 5-year-old VLBW (n = 28) and full-term (FT; n = 24) children. We found that VLBW children showed atypical recruitment of emotional face processing networks in theta (4–7 Hz) compared to FT children. VLBW children showed reduced theta connectivity during processing of angry faces only. This hypo-connected theta-band network was anchored in the left orbitofrontal and parietal regions, involved in the higher level processing of faces and emotion regulation. At the behavioural level, despite VLBW children performing within the normal range, FT children had significantly higher affect recognition scores. Our MEG results suggest a selective impairment in processing angry faces, which would negatively impact social functioning in VLBW children. In FT children, greater recruitment of this theta-band network was positively associated with improved affect recognition scores. Thus, our findings suggest an important role of theta oscillations in early face processing, deficits which may contribute to broader socio-emotional impairments in VLBW children.     

Invited Review: Factors associated with atypical brain development in preterm infants: insights from magnetic resonance imaging

Preterm birth (PTB) is a leading cause of neurodevelopmental and neurocognitive impairment in childhood and is closely associated with psychiatric disease. The biological and environmental factors that confer risk and resilience for healthy brain development and long-term outcome after PTB are uncertain, which presents challenges for risk stratification and for the discovery and evaluation of neuroprotective strategies. Neonatal magnetic resonance imaging reveals a signature of PTB that includes dysconnectivity of neural networks and atypical development of cortical and deep grey matter structures. Here we provide a brief review of perinatal factors that are associated with the MRI signature of PTB. We consider maternal and foetal factors including chorioamnionitis, foetal growth restriction, socioeconomic deprivation and prenatal alcohol, drug and stress exposures; and neonatal factors including co-morbidities of PTB, nutrition, pain and medication during neonatal intensive care and variation conferred by the genome/epigenome. Association studies offer the first insights into pathways to adversity and resilience after PTB. Future challenges are to analyse quantitative brain MRI data with collateral biological and environmental data in study designs that support causal inference, and ultimately to use the output of such analyses to stratify infants for clinical trials of therapies designed to improve outcome.     

Cognitive outcomes for extremely preterm/extremely low birth weight children in kindergarten

Our objectives were to examine cognitive outcomes for extremely preterm/extremely low birth weight (EPT/ELBW, gestational age <28 weeks and/or birth weight <1000 g) children in kindergarten and the associations of these outcomes with neonatal factors, early childhood neurodevelopmental impairment, and socioeconomic status (SES). The sample comprised a hospital-based 2001-2003 birth cohort of 148 EPT/ELBW children (mean birth weight 818 g; mean gestational age 26 weeks) and a comparison group of 111 term-born normal birth weight (NBW) classmate controls. Controlling for background factors, the EPT/ELBW group had pervasive deficits relative to the NBW group on a comprehensive test battery, with rates of cognitive deficits that were 3 to 6 times higher in the EPT/ELBW group. Deficits on a measure of response inhibition were found in 48% versus 10%, odds ratio (95% confidence interval) = 7.32 (3.32, 16.16), p < .001. Deficits on measures of executive function and motor and perceptual-motor abilities were found even when controlling for acquired verbal knowledge. Neonatal risk factors, early neurodevelopmental impairment, and lower SES were associated with higher rates of deficits within the EPT/ELBW group. The findings document both global and selective cognitive deficits in EPT/ELBW children at school entry and justify efforts at early identification and intervention.     

Neuroprotection with erythropoietin in preterm and/or low birth weight infants

Neonatal brain injury caused by extreme prematurity remains a great challenge for prevention. Erythropoietin (EPO) has shown neuroprotective effects in a series of neonatal experimental models and recent clinical trials of premature infants. In this meta-analysis of seven clinical trials, EPO was associated with a highly reproducible reduction in the risk of neurodevelopmental disability in preterm infants. However, there was no difference in the risk for morbidity, cerebral palsy, visual deficit, severe hearing deficit, necrotizing enterocolitis, intracranial hemorrhage and patent ductus arteriosus. The use of EPO, to some extent, is associated with reduction in neurodevelopmental disability in preterm infants. More double blind randomized controlled trials are needed to establish the best therapeutic approach for neuroprotection in preterm infants.     

Changes in brain function and anatomical structure following treatment of hyperbaric oxygen for visual pathway abnormalities in 16 cases★ Evaluation of functional magnetic resonance imaging combined with diffusion tensor imaging

BACKGROUND： There is a growing research focus on the combination of blood oxygenation level dependent functional magnetic resonance imaging （BOLD-fMRI） and diffusion tensor imaging （DTI） to evaluate visual cortical function and structural changes in the cerebrum, as well as morphological changes to the white matter fiber tracks, after visual pathway lesions. However, the combined application of BOLD-fMRI and DTI in treating of visual pathway abnormalities still requires further studies.
OBJECTIVE： To observe and evaluate the effects of hyperbaric oxygen on visual pathway abnormalities, and to evaluate the characteristics of cerebral function and anatomic structural changes by using BOLD-fMRI combined with DTI technique. DESIGN： Case contrast observation.
SETTING： Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA.
PARTICIPANTS： Sixteen patients （9 males and 7 females, 15-77 years old） with lateral or bilateral visual disorder induced by visual pathway lesions were selected from the Department of Neurology, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from January 2006 to May 2007. These patients comprised the lesion group. Measures of interventional therapy： hyperbaric oxygen of two normal atmospheres for three courses （10 d/course） and routine internal medicine treatment. In addition, 12 healthy subjects of similar sex and age to the lesion group were regarded as the control group. The control group underwent routine ophthalmological and ocular fundus examinations; diagnostic results were normal. The experiment received confirmed consent from the local ethic committee, and all patients provided informed consent.
METHODS： BOLD-fMRI and DTI manifestations in the lesion group were observed before and after hyperbaric oxygen intervention, and the results were compared with the control group. The subjects were positioned on their back, and BOLD-fMRI images were collected with the following GRE EPI sequence： TR = 2 000 ms, TE = 40     

Changes in brain function and anatomical structure following treatment of hyperbaric oxygen for visual pathway abnormalities In 16 cases Evaluation of functional magnetic resonance Imaging combined with diffusion tensor imaging

BACKGROUND:There is a growing research focus on the combination of blood oxygenation level dependent functional magnetic resonance imaging(BOLD-fMRI)and diffusion tensor imaging(DTI)to evaluate visual cortical function and structural changes in the cerebrum,as well as morphological changes to the white matter fiber tracks,after visual pathway lesions.However,the combined application of BOLD-fMRI and DTI in treating of visual pathway abnormalities still requires further studies. OBJECTIVE:To observe and evaluate the effects of hyperbaric oxygen on visual pathway abnormalities,and to evaluate the characteristics of cerebral function and anatomic structural changes by using BOLD-fMRI combined with DTI technique. DESIGN:Case contrast observation. SETTING:Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIPANTS:Sixteen patients(9 males and 7 females,15-77 years old)with lateral or bilateral visual disorder induced by visual pathway lesions were selected from the Department of Neurology,Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from January 2006 to May 2007.These patients comprised the lesion group.Measures of interventional therapy:hyperbaric oxygen of two normal atmospheres for three courses(10 d/course)and routine internal medicine treatment.In addition,12 healthy subjects of similar sex and age to the lesion group were regarded as the control group.The control group underwent routine ophthalmological and ocular fundus examinations; diagnostic results were normal. The experiment received confirmed consent from the local ethic committee,and all patients provided informed consent.METHODS:BOLD-fMRI and DTI manifestations in the lesion group were observed before and after hyperbaric oxygen intervention,and the results were compared with the control group.The subjects were positioned on their back,and BOLD-fMRI images were collected with the following GRE EPI sequence:TR＝ 2 000 ms,TE＝40 ms,layer thickness＝5 mm,and 20-layer successive scanning to cover the whole brain. While,DTI images were collected with SE EPI sequence of single excitation:TR＝10 000 ms,TE＝112 ms, layer thickness＝4 mm,layer spacing＝0.5 rnm,and a 30-layer successive scanning,matrix＝128×128.A diffusion gradient was applied at 13 directions,and one layer without diffusion weighted imaging was collected at b＝1 000 s/mm2.Numbers of activated voxels in cortical-activated regions,and fractional anisotropy in bilateral cerebral optical radiation regions,were calculated.Displacement,continuity,and destruction of fibrous tracts were analyzed. MAIN OUTCOME MEASURES:Results of BOLD-fMRI and DTI examinations.RESULTS:All 16 patients and 12 controls were included in the final analysis.①Numbers of activated voxels through the use of BOLD-fMRI:prior to hyperbaric oxygen therapy,the number of activated voxels in the bilateral cortex of occipital lobe were significantly less in the lesion group than in the control group(t＝3.23,P＜0.01).In addition,the number of activated voxels significantly increased after treatment compared to before treatment(t＝2.46,P＜0.05).②Fractional anisotropy in optical radiation regions of bilateral cerebrum:fractional anisotropy in the lesion group was significantly less than the control group (t＝2.89,P＜0.05).In addition,fractional anisotropy after treatment was significantly higher than before treatment(t＝2.48,P＜0.05).Moreover,fractional anisotropy of optical neuropathy was significantly higher in 6 patients in the lesion group than the occipital lobe optical central lesion(t＝2.35,P＜0.05).CONCLUSION:BOLD-fMRI combined with DTI can indicate the occurrence,development,and therapeutic course of action for optical pathway lesions.The results acquired from these methods can rovide information for function and structure,which can provide reliable verification in the treatment of cerebral function.     

Evaluation index for asymmetric ventricular size on brain magnetic resonance images in very low birth weight infants

Objective

Asymmetric ventriculomegaly is often evident on brain magnetic resonance imaging (MRI) in very low birth weight infants (VLBWI) and is interpreted as white matter injury. However, no evaluation index for asymmetric left-right and anterior-posterior ventricular sizes has been established.

Inflammation‐induced preterm birth alters neuronal morphology in the mouse fetal brain

Adverse neurological outcome is a major cause of long‐term morbidity in ex‐preterm children. To investigate the effect of parturition and inflammation on the fetal brain, we utilized two in vivo mouse models of preterm birth. To mimic the most common human scenario of preterm birth, we used a mouse model of intrauterine inflammation by intrauterine infusion of lipopolysaccharide (LPS). To investigate the effect of parturition on the immature fetal brain, in the absence of inflammation, we used a non‐infectious model of preterm birth by administering RU486. Pro‐inflammatory cytokines (IL‐10, IL‐1β, IL‐6 and TNF‐α) in amniotic fluid and inflammatory biomarkers in maternal serum and amniotic fluid were compared between the two models using ELISA. Pro‐inflammatory cytokine expression was evaluated in the whole fetal brains from the two models. Primary neuronal cultures from the fetal cortex were established from the different models and controls in order to compare the neuronal morphology. Only the intrauterine inflammation model resulted in an elevation of inflammatory biomarkers in the maternal serum and amniotic fluid. Exposure to inflammation‐induced preterm birth, but not non‐infectious preterm birth, also resulted in an increase in cytokine mRNA in whole fetal brain and in disrupted fetal neuronal morphology. In particular, Microtubule‐associated protein 2 (MAP2) staining was decreased and the number of dendrites was reduced (P < 0.001, ANOVA between groups). These results suggest that inflammation‐induced preterm birth and not the process of preterm birth may result in neuroinflammation and alter fetal neuronal morphology. © 2010 Wiley‐Liss, Inc.     

A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight

Objectives

To examine the relationship between antidepressant use in pregnancy and low birth weight (LBW) and preterm birth (PTB).

Data Sources and Study Selection

We searched English and non-English language articles via PubMed, CINAHL and PsychINFO (from their start dates through December 1st, 2012). We used the following keywords and their combinations: antidepressant, selective serotonin reuptake inhibitor (SSRI), pregnancy, antenatal, prenatal, birthweight, birth weight, preterm, prematurity, gestational age, fetal growth restriction, intrauterine growth restriction, and small-for-gestational age. Published studies were considered eligible if they examined exposure to antidepressant medication use during pregnancy and reported data on at least one birth outcome of interest: PTB (<37 weeks gestation) or LBW (<2500 g). Of the 222 reviewed studies, 28 published studies met the selection criteria.

Data Extraction

Two authors independently extracted study characteristics from eligible studies.

Results

Using random-effects models, antidepressant use in pregnancy was significantly associated with LBW (RR: 1.44, 95% confidence interval (CI): 1.21-1.70) and PTB (RR: 1.69, 95% CI: 1.52-1.88). Studies varied widely in design, populations, control groups and methods. There was a high level of heterogeneity as measured by I2 statistics for both outcomes examined. The relationship between antidepressant exposure in pregnancy and adverse birth outcomes did not differ significantly when taking into account drug type (SSRI vs. other or mixed) or study design (prospective vs. retrospective). There was a significant association between antidepressant exposure and PTB for different types of control status used (depressed, mixed or nondepressed).

Conclusions

Antidepressant use during pregnancy significantly increases the risk for LBW and PTB.     

Development of brain white matter and math computation ability in children born very preterm and full-term

Children born very preterm (VPT; <32 weeks’ gestation) have alterations in brain white matter and poorer math ability than full-term (FT) peers. Diffusion-weighted magnetic resonance imaging studies suggest a link between white matter microstructure and math in VPT and FT children, although longitudinal studies using advanced modelling are lacking. In a prospective longitudinal cohort of VPT and FT children we used Fixel-Based Analysis to investigate associations between maturation of white matter fibre density (FD), fibre-bundle cross‐section (FC), and combined fibre density and cross‐section (FDC) and math computation ability at 7 (n = 136 VPT; n = 32 FT) and 13 (n = 130 VPT; n = 44 FT) years, as well as between change in white matter and math computation ability from 7 to 13 years (n = 103 VPT; n = 21 FT). In both VPT and FT children, higher FD, FC and FDC in visual, sensorimotor and cortico-thalamic/thalamo-cortical white matter tracts were associated with better math computation ability at 7 and 13 years. Longitudinally, accelerated maturation of the posterior body of the corpus callosum (FDC) was associated with greater math computation development. White matter-math associations were similar for VPT and FT children. In conclusion, white matter maturation is associated with math computation ability across late childhood, irrespective of birth group.     

Diffusion-weighted imaging in brain aspergillosis

Brain aspergillosis is a rare pathology, occurring mainly in immunocompromised patients, responsible for multiple cerebral septic infarctions. Some researchers have described magnetic resonance (MR) findings in cerebral invasive aspergillosis, but diffusion-weighted imaging (DWI) has rarely been reported, especially in typical non-enhancing lesions, while it may be helpful for early differential diagnosis and may allow earlier antifungal treatment. We describe three cases of patients presenting brain aspergillosis, with MR imaging including diffusion-weighted sequences and apparent diffusion coefficient (ADC) cartography. The three patients described in this study presented a total of 23 circular lesions, and one patient presented an infarction area in the territory of the right middle cerebral artery. Lesions were ring-enhancing for one patient, and presented no enhancement for the other two. Eleven lesions were very bright on DWI, with reduced ADC values. Twelve lesions, either enhancing or not enhancing, presented a 'target-like' aspect with central and peripheral hypointense areas on DWI, corresponding to higher ADC value areas, and intermediate marked hypersignal on DWI. This typical aspect of aspergillosis lesions on DWI may allow early diagnosis and treatment of cerebral aspergillosis, and is helpful for differentiating aspergillosis lesions from other infectious or malignant lesions affecting immunocompromised patients.     

Emerging atypical connectivity networks for processing angry and fearful faces in very preterm born children

Very preterm born (VPT) children are those born before 32/40 weeks' gestational age and comprise 10% of the 15 million babies born prematurely worldwide each year. Due to advancements in neonatal medicine, the survival rate of VPT birth has increased, but few studies have investigated the nonmedical, social‐cognitive morbidities that affect these children. In this study, we examined emotional face processing networks in VPT compared to age and sex matched full‐term born (FT) children. Magnetoencephalography (MEG) was used to test VPT and FT born children at 6 years (n = 78) and 8 years (n = 83). Children were assessed using an implicit emotion face‐processing task. Happy, fearful, and angry faces were presented for 150 ms, but children were asked to respond by button press to the location of a control pixelated image of the face displayed on the side of the screen opposite to the face. Children rated the valence of the images on a five‐point scale. Group differences showed that VPT children rated angry faces more positively than their FT peers. VPT children had reduced connectivity for angry and fearful faces at 8 years in networks including regions such as the bilateral amygdala, superior temporal sulci, and anterior cingulate gyrus. Interventions should target both emotion recognition, as well as higher cognitive processes related to emotional control and thinking about one's own emotions.