Cognitively healthy APOE4/4 carriers show white matter impairment associated with serum NfL and amyloid-PET.

Except for aging, carrying the APOE ε4 allele (APOE4) is the most important risk factor for sporadic Alzheimer's disease. APOE4 carriers may have reduced capacity to recycle lipids, resulting in white matter microstructural abnormalities. In this study, we evaluated whether white matter impairment measured by diffusion tensor imaging (DTI) differs between healthy individuals with a different number of APOE4 alleles, and whether white matter impairment associates with brain beta-amyloid (Aß) load and serum levels of neurofilament light chain (NfL). We studied 96 participants (APOE3/3, N = 37; APOE3/4, N = 39; APOE4/4, N = 20; mean age 70.7 (SD 5.22) years, 63% females) with a brain MRI including a DTI sequence (N = 96), Aß-PET (N = 89) and a venous blood sample for the serum NfL concentration measurement (N = 88). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) in six a priori-selected white matter regions-of-interest (ROIs) were compared between the groups using ANCOVA, with sex and age as covariates. A voxel-weighted average of FA, MD, RD and AxD was calculated for each subject, and correlations with Aß-PET and NfL levels were evaluated. APOE4/4 carriers exhibited a higher MD and a higher RD in the body of corpus callosum than APOE3/4 (p = 0.0053 and p = 0.0049, respectively) and APOE3/3 (p = 0.026 and p = 0.042). APOE4/4 carriers had a higher AxD than APOE3/4 (p = 0.012) and APOE3/3 (p = 0.040) in the right cingulum adjacent to cingulate cortex. In the total sample, composite MD, RD and AxD positively correlated with the cortical Aß load (r = 0.26 to 0.33, p < 0.013 for all) and with serum NfL concentrations (r = 0.31 to 0.36, p < 0.0028 for all). In conclusion, increased local diffusivity was detected in cognitively unimpaired APOE4/4 homozygotes compared to APOE3/4 and APOE3/3 carriers, and increased diffusivity correlated with biomarkers of Alzheimer's disease and neurodegeneration. White matter impairment seems to be an early phenomenon in the Alzheimer's disease pathologic process in APOE4/4 homozygotes.

A novel variant in CYFIP2 in a girl with severe disabilities and bilateral perisylvian polymicrogyria.

Bilateral perisylvian polymicrogyria (BPP) is a structural malformation of the cerebral cortex that can be caused by several genetic abnormalities. The most common clinical manifestations of BPP include intellectual disability and epilepsy. Cytoplasmic FMRP-interacting protein 2 (CYFIP2) is a protein that interacts with the fragile X mental retardation protein (FMRP). CYFIP2 variants can cause various brain structural abnormalities with the most common clinical manifestations of intellectual disability, epileptic encephalopathy and dysmorphic features. We present a girl with multiple disabilities and BPP caused by a heterozygous, novel, likely pathogenic variant (c.1651G>C: p.(Val551Leu) in the CYFIP2 gene. Our case report broadens the spectrum of genetic diversity associated with BPP by incorporating CYFIP2.

Bone marrow metabolism is affected by body weight and response to exercise training varies according to anatomical location.

AIM: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. METHODS: We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co-twins 7.6 kg/m2 ; eight female pairs). Ten pairs completed the 6-month long training intervention. We measured lumbar vertebral and femoral BM insulin-stimulated glucose uptake (GU) using 18 F-FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. RESULTS: At baseline, heavier co-twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co-twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole-body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co-twins (p = .06) while there was no change in leaner co-twins. CONCLUSIONS: In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co-twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity.

Major brain injuries at term continue to influence DTI parameters in adolescents born very preterm: a 13-year follow-up study.

BACKGROUND: Major brain injuries in structural brain magnetic resonance imaging (MRI) at term affect concurrent diffusion tensor imaging (DTI) parameters in very preterm infants. White matter is known to gradually maturate along with increasing gestational age, which is characterized by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). PURPOSE: To study the difference between DTI parameters at term and 13 years in adolescents born very preterm with and without major pathologies in structural brain MRI at term. MATERIAL AND METHODS: Adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) in 2004-2006 at Turku University Hospital, Finland were included. We evaluated FA and MD at term and 13 years in 18 regions of interest using the JHU-neonate-SS atlas to compare the differences in these parameters between adolescents with and without major injuries identified on MRI at term. RESULTS: A total of 24 adolescents underwent brain MRI including DTI both at term and 13 years. Adolescents with major brain injury pathologies (n = 6) in structural MRI at term had decreased FA in the left corpus callosum and right cingulate gyrus part, and increased MD in the left corpus callosum, right anterior limb of internal capsule, and right posterior limb of the internal capsule at 13 years, in comparison with adolescents without major brain injuries (n = 18) in structural MRI at term. CONCLUSION: Our findings suggest that major brain injuries identified on structural MRI at term affect brain maturation, with adverse effects in FA and MD still during adolescence.

Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial.

BACKGROUND: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA. METHODS: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA. RESULTS: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups. CONCLUSIONS: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00879892.

Maternal psychological distress associates with alterations in resting-state low-frequency fluctuations and distal functional connectivity of the neonate medial prefrontal cortex.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. Twenty-one neonates (nine female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHo/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex-dependent way.

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences.

Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics.

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tract-based spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.

Structural brain correlates of non-verbal cognitive ability in 5-year-old children: Findings from the FinnBrain birth cohort study.

Non-verbal cognitive ability predicts multiple important life outcomes, for example, school and job performance. It has been associated with parieto-frontal cortical anatomy in prior studies in adult and adolescent populations, while young children have received relatively little attention. We explored the associations between cortical anatomy and non-verbal cognitive ability in 165 5-year-old participants (mean scan age 5.40 years, SD 0.13; 90 males) from the FinnBrain Birth Cohort study. T1-weighted brain magnetic resonance images were processed using FreeSurfer. Non-verbal cognitive ability was measured using the Performance Intelligence Quotient (PIQ) estimated from the Block Design and Matrix Reasoning subtests from the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). In vertex-wise general linear models, PIQ scores associated positively with volumes in the left caudal middle frontal and right pericalcarine regions, as well as surface area in left the caudal middle frontal, left inferior temporal, and right lingual regions. There were no associations between PIQ and cortical thickness. To the best of our knowledge, this is the first study to examine structural correlates of non-verbal cognitive ability in a large sample of typically developing 5-year-olds. The findings are generally in line with prior findings from older age groups, with the important addition of the positive association between volume / surface area in the right medial occipital region and non-verbal cognitive ability. This finding adds to the literature by discovering a new brain region that should be considered in future studies exploring the role of cortical structure for cognitive development in young children.

Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrest-a substudy of the XeHypotheca trial.

PURPOSE: We compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA). METHODS: The predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 - 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory. RESULTS: The predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 - 0.88)), or NSE at 72 h (0.85 (0.76 - 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), p = 0.037). CONCLUSION: None of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use. TRIAL REGISTRATION: ClinicalTrials.gov NCT00879892, April 13, 2009.

Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system.

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.

Serotonergic and dopaminergic control of impulsivity in gambling disorder.

Gambling disorder (GD) is major public health issue. The disorder is often characterized by elevated impulsivity with evidence from analogous substance use disorders underlining prominent roles of brain monoamines in addiction susceptibility and outcome. Critically, GD allows the study of addiction mechanisms without the confounder of the effects of chronic substances. Here, we assessed the roles of striatal dopamine transporter binding and extrastriatal serotonin transporter binding in GD as a function of impulsivity using [123 I]FP-CIT SPECT imaging in 20 older adults with GD (DSM-5 criteria; mean age 64 years) and 40 non-GD age- and sex-matched controls. We focused on GD in older individuals because there are prominent age-related changes in neurotransmitter function and because there are no reported neuroimaging studies of GD in older adults. Volume-of-interest-based and voxelwise analyses were performed. GD patients scored clearly higher on impulsivity and had higher tracer binding in the ventromedial prefrontal cortex than controls (p < 0.001), likely reflecting serotonin transporter activity. The binding in the medial prefrontal cortex positively correlated with impulsivity over the whole sample (r = 0.62, p < 0.001) as well as separately in GD patients (r = 0.46, p = 0.04) and controls (r = 0.52, p < 0.001). Striatal tracer binding, reflecting dopamine transporter activity was also positively correlated with impulsivity but showed no group differences. These findings highlight the role of prefrontal serotonergic function in GD and impulsivity. They identify cerebral coordinates of a potential target for neuromodulation for both GD and high impulsivity, a core phenotypic dimensional cognitive marker in addictions.

Infants' sex affects neural responses to affective touch in early infancy.

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.

Subcortical and hippocampal brain segmentation in 5-year-old children: Validation of FSL-FIRST and FreeSurfer against manual segmentation.

Developing accurate subcortical volumetric quantification tools is crucial for neurodevelopmental studies, as they could reduce the need for challenging and time-consuming manual segmentation. In this study, the accuracy of two automated segmentation tools, FSL-FIRST (with three different boundary correction settings) and FreeSurfer, were compared against manual segmentation of the hippocampus and subcortical nuclei, including the amygdala, thalamus, putamen, globus pallidus, caudate and nucleus accumbens, using volumetric and correlation analyses in 80 5-year-olds. Both FSL-FIRST and FreeSurfer overestimated the volume on all structures except the caudate, and the accuracy varied depending on the structure. Small structures such as the amygdala and nucleus accumbens, which are visually difficult to distinguish, produced significant overestimations and weaker correlations with all automated methods. Larger and more readily distinguishable structures such as the caudate and putamen produced notably lower overestimations and stronger correlations. Overall, the segmentations performed by FSL-FIRST's default pipeline were the most accurate, whereas FreeSurfer's results were weaker across the structures. In line with prior studies, the accuracy of automated segmentation tools was imperfect with respect to manually defined structures. However, apart from amygdala and nucleus accumbens, FSL-FIRST's agreement could be considered satisfactory (Pearson correlation > 0.74, intraclass correlation coefficient (ICC) > 0.68 and Dice score coefficient (DSC) > 0.87) with highest values for the striatal structures (putamen, globus pallidus, caudate) (Pearson correlation > 0.77, ICC > 0.87 and DSC > 0.88, respectively). Overall, automated segmentation tools do not always provide satisfactory results, and careful visual inspection of the automated segmentations is strongly advised.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins.

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study.

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2-5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes.

Differences in brain changes between adults with childhood-onset epilepsy and controls: A prospective population-based study.

PURPOSE: To determine the impact of childhood-onset uncomplicated epilepsy (COE) on brain aging over 50-year prospective follow-up. METHODS: A population-based cohort of 41 aging subjects with COE and their 46 matched controls participated in a detailed in-person prospective assessment in 2012 and 2017 to characterize ongoing changes in the aging brain. RESULTS: The mean age of the COE participants was 63.2 years (SD 4.14, median 63.2, range 55.8-70.6) and 63.0 years (mean, SD 4.13, median 63.3, range 56.0-69.9) years for controls. Neurologic signs were significantly more common in COE participants not in remission (p = .015), and the most frequent abnormalities were cerebellar signs (p < .001). Neurologic signs in general (p = .008) and cerebellar signs in particular (p = .018) were significantly more common in focal than in generalized epilepsies. MRI white matter abnormalities were significantly associated with absence of vocational education (p = .011), and MRI hippocampal atrophy in COE subjects was associated with arterial hypertension versus normal blood pressure (p = .017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and in the controls from the 2012 to 2017 study. CONCLUSIONS: At ultra-long-term follow-up, clinical and neuroimaging findings show tendencies to brain aging that is more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy.

Brain volumes and white matter microstructure in 8- to 10-year-old children born with fetal growth restriction.

BACKGROUND: Fetal growth restriction caused by placental insufficiency is associated with increased risk of poor neurodevelopment, even in the absence of specific perinatal brain injury. Placental insufficiency leads to chronic hypoxaemia that may alter cerebral tissue organisation and maturation. OBJECTIVE: The aim of this study was to assess the effects fetal growth restriction and fetal haemodynamic abnormalities have on brain volumes and white matter microstructure at early school age. MATERIALS AND METHODS: This study examined 32 children born with fetal growth restriction at 24 to 40 gestational weeks, and 27 gestational age-matched children, who were appropriate for gestational age. All children underwent magnetic resonance imaging (MRI) at the age of 8-10 years. Cerebral volumes were analysed, and tract-based spatial statistics and atlas-based analysis of white matter were performed on 17 children born with fetal growth restriction and 14 children with birth weight appropriate for gestational age. RESULTS: Children born with fetal growth restriction demonstrated smaller total intracranial volumes compared to children with normal fetal growth, whereas no significant differences in grey or white matter volumes were detected. On atlas-based analysis of white matter, children born with fetal growth restriction demonstrated higher mean and radial diffusivity values in large white matter tracts when compared to children with normal fetal growth. CONCLUSION: Children ages 8-10 years old born with fetal growth restriction demonstrated significant changes in white matter microstructure compared to children who were appropriate for gestational age, even though no differences in grey and white matter volumes were detected. Poor fetal growth may impact white matter maturation and lead to neurodevelopmental impairment later in life.

The outcomes of recurrent wide-necked intracranial aneurysms treated with the Woven EndoBridge (WEB): A retrospective bicenter study.

BACKGROUND: The Woven EndoBridge (WEB) is a device for the treatment of intracranial wide-necked bifurcation aneurysms. The safety and effectiveness of WEB for intracranial aneurysms have both been evaluated in previous trials. Our aim was to study the outcomes of recurrent intracranial aneurysms (IAs) treated with WEB. METHODS: Clinical and radiological outcomes of patients with a wide-necked aneurysm recurrence, which was treated with WEB device, were assessed. Imaging follow-up was performed with digital subtraction angiography and/or magnetic resonance angiography. Aneurysm occlusion was determined using by the Raymond-Roy Occlusion Classification (RROC). RROC 1 and RROC 2 were considered as adequate radiological outcome. RESULTS: Twenty-two patients with 23 recurrent IAs were treated with WEB. Of which, 17 of recurrent IAs (74%) previously treated by coiling, three (13%) by clipping and three (13%) by WEB. The most common location of the recurrent IA was the middle cerebral artery (n = 10, 43%). Endovascular treatment with WEB alone was suitable for 20 recurrent IAs (87%). Ancillary devices were also used: coils in two (9%), and a stent in one (4%). Radiological follow-up results available for all patients (range: 3-60 months; median 24 months). Adequate occlusion (RROC I and II) was achieved in 20 recurrent IAs (87%). A hemorrhagic complication occurred 2 weeks post treatment in one patient (5%). CONCLUSIONS: WEB could be an effective treatment with low rates of complications for challenging cases of recurrent wide-necked IAs.

Functional Magnetic Resonance Imaging during Visual Perception Tasks in Adolescents Born Prematurely.

OBJECTIVES: Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better understand the neural substrates of the visual perceptual impairments, we compared behavioral performance and brain activations during visual perception tasks in adolescents born very preterm (birth weight ≤1500 g or gestational age <32 weeks) and full-term. METHODS: Tasks assessing visual closure, discrimination of a deviating figure, and discrimination of figure and ground from the Motor-Free Visual Perception Test, Third Edition were performed by participants born very preterm (n = 37) and full-term (n = 34) at 12 years of age during functional magnetic resonance imaging. RESULTS: Behavioral performance in the visual perception tasks did not differ between the groups. However, during the visual closure task, brain activation was significantly stronger in the group born very preterm in a number of areas including the frontal, anterior cingulate, temporal, and posterior medial parietal/cingulate cortices, as well as in parts of the cerebellum, thalamus, and caudate nucleus. CONCLUSIONS: Differing activations during the visual closure task potentially reflect a compensatory neural process related to premature birth or lesser neural efficiency or may be a result of the use of compensatory behavioral strategies in the study group born very preterm.